NRXN1neurexin 1
Autism Reports / Total Reports
64 / 118Rare Variants / Common Variants
232 / 5Aliases
NRXN1, DKFZp313P2036, FLJ35941, Hs.22998, KIAA0578, PTHSL2Associated Syndromes
Pitt-Hopkins-like syndrome 2, Tourette syndrome, Pitt-Hopkins-like syndrome 2, DD, ID, epilepsy/seiChromosome Band
2p16.3Associated Disorders
SCZ, DD/NDD, ADHD, ID, EP, BPD, EPS, ASDGenetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association, FunctionalRelevance to Autism
Recurrent mutations in the NRXN1 gene have been identified in individuals with ASD as described below. Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
Molecular Function
Neurexins function in the vertebrate nervous system as cell adhesion molecules and receptors. Two neurexin genes are among the largest known in human (NRXN1 and NRXN3). By using alternate promoters, splice sites and exons, predictions of hundreds or even thousands of distinct mRNAs have been made.
External Links
SFARI Genomic Platforms
Reports related to NRXN1 (118 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Neurexin mediates the assembly of presynaptic terminals | Dean C , et al. (2003) | No | - |
| 2 | Recent Recommendation | Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex | Chih B , et al. (2006) | No | - |
| 3 | Primary | High frequency of neurexin 1beta signal peptide structural variants in patients with autism | Feng J , et al. (2006) | Yes | - |
| 4 | Recent Recommendation | Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95-neuroligin | Futai K , et al. (2007) | No | - |
| 5 | Positive Association | Mapping autism risk loci using genetic linkage and chromosomal rearrangements | Autism Genome Project Consortium , et al. (2007) | Yes | - |
| 6 | Recent Recommendation | Silencing of neuroligin function by postsynaptic neurexins | Taniguchi H , et al. (2007) | No | - |
| 7 | Recent Recommendation | A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha | Zahir FR , et al. (2007) | No | - |
| 8 | Positive Association | Disruption of neurexin 1 associated with autism spectrum disorder | Kim HG , et al. (2008) | Yes | - |
| 9 | Positive Association | Neurexin 1alpha structural variants associated with autism | Yan J , et al. (2008) | Yes | - |
| 10 | Support | Recurrent CNVs disrupt three candidate genes in schizophrenia patients | Vrijenhoek T , et al. (2008) | No | - |
| 11 | Recent Recommendation | Disruption of the neurexin 1 gene is associated with schizophrenia | Rujescu D , et al. (2008) | No | - |
| 12 | Recent Recommendation | Presynaptic targeting of alpha4beta 2 nicotinic acetylcholine receptors is regulated by neurexin-1beta | Cheng SB , et al. (2009) | No | - |
| 13 | Recent Recommendation | Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments | Etherton MR , et al. (2009) | Yes | - |
| 14 | Support | CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila | Zweier C , et al. (2009) | No | ID, epilepsy |
| 15 | Recent Recommendation | Sensory regulation of neuroligins and neurexin I in the honeybee brain | Biswas S , et al. (2010) | No | - |
| 16 | Support | Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay | Winiowiecka-Kowalnik B , et al. (2010) | Yes | - |
| 17 | Positive Association | Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders | Ching MS , et al. (2010) | Yes | - |
| 18 | Recent Recommendation | Neurexins physically and functionally interact with GABA(A) receptors | Zhang C , et al. (2010) | No | - |
| 19 | Support | Functional impact of global rare copy number variation in autism spectrum disorders | Pinto D , et al. (2010) | Yes | - |
| 20 | Recent Recommendation | Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum | Uemura T , et al. (2010) | No | - |
| 21 | Recent Recommendation | Splice form dependence of beta-neurexin/neuroligin binding interactions | Koehnke J , et al. (2010) | No | - |
| 22 | Recent Recommendation | Direct measure of the de novo mutation rate in autism and schizophrenia cohorts | Awadalla P , et al. (2010) | No | - |
| 23 | Support | Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia | Gauthier J , et al. (2011) | No | ASD, ID |
| 24 | Recent Recommendation | Modeling the functional genomics of autism using human neurons | Konopka G , et al. (2011) | No | - |
| 25 | Recent Recommendation | Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders | Voineskos AN , et al. (2011) | Yes | SCZ |
| 26 | Recent Recommendation | Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1 | Gregor A , et al. (2011) | No | - |
| 27 | Support | Compound heterozygous deletion of NRXN1 causing severe developmental delay with early onset epilepsy in two sisters | Harrison V , et al. (2011) | No | Epilepsy |
| 28 | Support | Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders | Duong L , et al. (2012) | Yes | MR, Epilepsy |
| 29 | Positive Association | Mutation analysis of the NRXN1 gene in a Chinese autism cohort | Liu Y , et al. (2012) | Yes | - |
| 30 | Support | Mutations affecting synaptic levels of neurexin-1? in autism and mental retardation | Camacho-Garcia RJ , et al. (2012) | Yes | ID |
| 31 | Support | De novo gene disruptions in children on the autistic spectrum | Iossifov I , et al. (2012) | Yes | - |
| 32 | Recent Recommendation | Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions | Schaaf CP , et al. (2012) | Yes | ADHD, epilepsy |
| 33 | Recent Recommendation | Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1? and activation of fibroblast growth factor receptor-1 | Gjrlund MD , et al. (2012) | No | - |
| 34 | Support | Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion | Onat OE , et al. (2012) | Yes | - |
| 35 | Support | Rate of de novo mutations and the importance of father's age to disease risk | Kong A , et al. (2012) | Yes | - |
| 36 | Support | 2p16.3 microdeletion with partial deletion of the neurexin-1 gene in a female with developmental delays, short stature, and a congenital diaphragmatic hernia | Bermudez-Wagner K , et al. (2012) | No | - |
| 37 | Support | A discovery resource of rare copy number variations in individuals with autism spectrum disorder | Prasad A , et al. (2013) | Yes | - |
| 38 | Support | Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy | Mller RS , et al. (2013) | No | ID |
| 39 | Recent Recommendation | Neurexin regulates visual function via mediating retinoid transport to promote rhodopsin maturation | Tian Y , et al. (2013) | No | - |
| 40 | Support | Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder | Girirajan S , et al. (2013) | Yes | - |
| 41 | Support | Investigation of NRXN1 deletions: clinical and molecular characterization | Dabell MP , et al. (2013) | No | ASD, ADHD, Epilepsy |
| 42 | Support | Identification of rare copy number variants in high burden schizophrenia families | Van Den Bossche MJ , et al. (2013) | No | - |
| 43 | Support | Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature | Bna F , et al. (2013) | Yes | Epilepsy |
| 44 | Support | CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1 | Nag A , et al. (2013) | No | - |
| 45 | Recent Recommendation | Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models | Zeng L , et al. (2013) | No | - |
| 46 | Support | Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing | Jiang YH , et al. (2013) | Yes | - |
| 47 | Support | Identification of candidate intergenic risk loci in autism spectrum disorder | Walker S and Scherer SW (2013) | Yes | - |
| 48 | Support | Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with autism spectrum disorder | Koshimizu E , et al. (2013) | Yes | ID, epilepsy |
| 49 | Support | A survey of rare coding variants in candidate genes in schizophrenia by deep sequencing | Hu X , et al. (2013) | No | - |
| 50 | Support | Etiological yield of SNP microarrays in idiopathic intellectual disability | Utine GE , et al. (2014) | No | ASD or autistic features, epilepsy |
| 51 | Support | Fraternal twins with autism, severe cognitive deficit, and epilepsy: diagnostic role of chromosomal microarray analysis | Imitola J , et al. (2014) | No | ASD, ID, epilepsy |
| 52 | Support | Refining analyses of copy number variation identifies specific genes associated with developmental delay | Coe BP , et al. (2014) | Yes | - |
| 53 | Recent Recommendation | Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins | Schreiner D , et al. (2014) | No | - |
| 54 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 55 | Support | Recurrent de novo mutations implicate novel genes underlying simplex autism risk | O'Roak BJ , et al. (2014) | Yes | - |
| 56 | Support | A boy with dysmorphic features, intellectual disability, and biallelic homozygous deletion in NRXN1 | Holmquist P (2014) | No | - |
| 57 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | Hypotonia |
| 58 | Support | A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion | Vias-Jornet M , et al. (2015) | No | ASD, BPD, ADHD |
| 59 | Recent Recommendation | Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging | Jenkins AK , et al. (2015) | No | - |
| 60 | Support | Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder | Tammimies K , et al. (2015) | Yes | - |
| 61 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
| 62 | Support | Frequency and Complexity of De Novo Structural Mutation in Autism | Brandler WM , et al. (2016) | Yes | - |
| 63 | Recent Recommendation | Molecular characterization of NRXN1 deletions from 19,263 clinical microarray cases identifies exons important for neurodevelopmental disease expression | Lowther C , et al. (2016) | Yes | - |
| 64 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort | Wang T , et al. (2016) | Yes | - |
| 65 | Support | The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies | Redin C , et al. (2016) | No | - |
| 66 | Support | Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases | Stessman HA , et al. (2017) | Yes | - |
| 67 | Support | Mutation analysis of the NRXN1 gene in autism spectrum disorders | Onay H , et al. (2017) | Yes | - |
| 68 | Recent Recommendation | Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome | Huang AY , et al. (2017) | No | - |
| 69 | Support | Variable phenotype expression in a family segregating microdeletions of the NRXN1 and MBD5 autism spectrum disorder susceptibility genes | Woodbury-Smith M , et al. (2017) | Yes | Macrocephaly |
| 70 | Support | Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders | Li J , et al. (2017) | Yes | - |
| 71 | Support | Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder | Takata A , et al. (2018) | Yes | - |
| 72 | Recent Recommendation | A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies | Liu Y , et al. (2018) | Yes | - |
| 73 | Recent Recommendation | NRXN1 deletion syndrome; phenotypic and penetrance data from 34 families | Al Shehhi M , et al. (2018) | No | ASD, epilepsy/seizures |
| 74 | Support | Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model | Guo H , et al. (2018) | Yes | - |
| 75 | Support | Both rare and common genetic variants contribute to autism in the Faroe Islands | Leblond CS , et al. (2019) | Yes | - |
| 76 | Recent Recommendation | Phenotypic spectrum of NRXN1 mono- and bi-allelic deficiency: A systematic review | Castronovo P , et al. (2019) | No | - |
| 77 | Support | Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developmental disorders | Schluth-Bolard C , et al. (2019) | No | Behavioral abnormalities |
| 78 | Support | Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population | Monies D , et al. (2019) | No | Stereotypies |
| 79 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
| 80 | Support | Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder | Munnich A , et al. (2019) | Yes | - |
| 81 | Recent Recommendation | Neuronal impact of patient-specific aberrant NRXN1? splicing | Flaherty E , et al. (2019) | No | - |
| 82 | Support | Increased Ca 2+ signaling in NRXN1? +/- neurons derived from ASD induced pluripotent stem cells | Avazzadeh S , et al. (2020) | Yes | - |
| 83 | Support | The clinical relevance of intragenic NRXN1 deletions | Cosemans N , et al. (2020) | No | - |
| 84 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 85 | Support | Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use | Husson T , et al. (2020) | Yes | - |
| 86 | Support | Further insight into the neurobehavioral pattern of children carrying the 2p16.3 heterozygous deletion involving NRXN1: Report of five new cases | Alfieri P et al. (2020) | Yes | Epilepsy/seizures |
| 87 | Support | Genome-wide detection of tandem DNA repeats that are expanded in autism | Trost B et al. (2020) | Yes | - |
| 88 | Support | Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia | Ishizuka K et al. (2020) | Yes | - |
| 89 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | ID |
| 90 | Support | - | Cameli C et al. (2021) | Yes | DD |
| 91 | Support | - | Ohashi K et al. (2021) | Yes | - |
| 92 | Support | - | Taà Ÿkñran EZ et al. (2021) | No | ADHD |
| 93 | Support | - | Pak C et al. (2021) | No | - |
| 94 | Support | - | Kight KE et al. (2021) | Yes | - |
| 95 | Support | - | Liu Y et al. (2021) | Yes | - |
| 96 | Support | - | Avazzadeh S et al. (2021) | Yes | - |
| 97 | Support | - | Chen S et al. (2021) | Yes | Epilepsy/seizures |
| 98 | Support | - | Hughes RB et al. (2022) | No | - |
| 99 | Support | - | Levy KA et al. (2022) | No | - |
| 100 | Support | - | Zhou X et al. (2022) | Yes | - |
| 101 | Support | - | Janz P et al. (2022) | No | - |
| 102 | Support | - | Chan AJS et al. (2022) | Yes | - |
| 103 | Support | - | Bentez-Burraco A et al. (2023) | No | Autistic features |
| 104 | Support | - | Wu D et al. (2023) | No | - |
| 105 | Support | - | Xu B et al. (2023) | Yes | - |
| 106 | Support | - | Hu C et al. (2023) | Yes | - |
| 107 | Support | - | Sebastian R et al. (2023) | No | - |
| 108 | Support | - | Lu H et al. (2023) | Yes | - |
| 109 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
| 110 | Support | - | Sheth F et al. (2023) | Yes | DD, ID |
| 111 | Support | - | Ana Karen Sandoval-Talamantes et al. (2023) | Yes | - |
| 112 | Support | - | E J Marijke Achterberg et al. () | Yes | - |
| 113 | Support | - | Mara H Cowen et al. (2024) | No | - |
| 114 | Support | - | Hamide Betul Gerik-Celebi et al. () | No | ASD, epilepsy/seizures |
| 115 | Positive Association | - | Yi Yang et al. () | Yes | - |
| 116 | Support | - | Axel Schmidt et al. (2024) | No | - |
| 117 | Support | - | Karen Lob et al. () | Yes | ADHD, DD, ID, epilepsy/seizures |
| 118 | Highly Cited | Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules | Nguyen T and Sdhof TC (1997) | No | - |
Rare Variants (232)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | - | - | - | 18945720 | Rujescu D , et al. (2008) | |
| - | - | copy_number_loss | Unknown | - | - | 39136901 | Karen Lob et al. () | |
| - | - | copy_number_loss | De novo | - | - | 23533028 | Bna F , et al. (2013) | |
| - | - | copy_number_loss | Unknown | - | - | 23533028 | Bna F , et al. (2013) | |
| - | - | copy_number_loss | Unknown | - | - | 23533600 | Nag A , et al. (2013) | |
| - | - | missense_variant | De novo | - | - | 29754769 | Liu Y , et al. (2018) | |
| - | - | splicing_variant | De novo | - | - | 29754769 | Liu Y , et al. (2018) | |
| - | - | copy_number_loss | Unknown | - | - | 34800434 | Chen S et al. (2021) | |
| - | - | copy_number_gain | - | - | - | 18940311 | Vrijenhoek T , et al. (2008) | |
| - | - | copy_number_loss | - | - | - | 18940311 | Vrijenhoek T , et al. (2008) | |
| - | - | copy_number_gain | De novo | - | - | 27841880 | Redin C , et al. (2016) | |
| - | - | copy_number_loss | De novo | - | - | 33590427 | Ohashi K et al. (2021) | |
| - | - | copy_number_loss | De novo | - | - | 18057082 | Zahir FR , et al. (2007) | |
| - | - | copy_number_loss | De novo | - | - | 21827697 | Gregor A , et al. (2011) | |
| - | - | copy_number_loss | De novo | - | - | 32658356 | Alfieri P et al. (2020) | |
| - | - | copy_number_loss | De novo | - | - | 22617343 | Schaaf CP , et al. (2012) | |
| - | - | copy_number_loss | Unknown | - | - | 22617343 | Schaaf CP , et al. (2012) | |
| - | - | copy_number_loss | De novo | - | - | 23495017 | Dabell MP , et al. (2013) | |
| - | - | copy_number_loss | Unknown | - | - | 23495017 | Dabell MP , et al. (2013) | |
| - | - | copy_number_loss | Unknown | - | - | 31406558 | Munnich A , et al. (2019) | |
| - | - | minisatellite | Unknown | - | Simplex | 32717741 | Trost B et al. (2020) | |
| - | - | copy_number_loss | De novo | - | - | 26325558 | Tammimies K , et al. (2015) | |
| - | - | copy_number_loss | De novo | - | - | 30031152 | Al Shehhi M , et al. (2018) | |
| - | - | copy_number_loss | Unknown | - | - | 30031152 | Al Shehhi M , et al. (2018) | |
| - | - | copy_number_loss | Unknown | - | - | 39039281 | Axel Schmidt et al. (2024) | |
| - | - | copy_number_loss | De novo | - | Simplex | 23533600 | Nag A , et al. (2013) | |
| - | - | loss_of_function_variant | De novo | - | - | 29754769 | Liu Y , et al. (2018) | |
| - | - | translocation | De novo | - | - | 30923172 | Schluth-Bolard C , et al. (2019) | |
| - | - | copy_number_loss | Familial | Maternal | - | 23533028 | Bna F , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | - | 23533028 | Bna F , et al. (2013) | |
| - | - | copy_number_gain | De novo | - | Simplex | 20531469 | Pinto D , et al. (2010) | |
| - | - | copy_number_loss | De novo | - | Unknown | 20531469 | Pinto D , et al. (2010) | |
| - | - | copy_number_loss | De novo | - | Simplex | 20468056 | Ching MS , et al. (2010) | |
| - | - | copy_number_loss | Unknown | - | Simplex | 20468056 | Ching MS , et al. (2010) | |
| - | - | copy_number_loss | Unknown | - | Unknown | 23275889 | Prasad A , et al. (2013) | |
| - | - | copy_number_loss | De novo | - | Simplex | 32094338 | Husson T , et al. (2020) | |
| - | - | copy_number_loss | Apparently de novo | - | - | 23533028 | Bna F , et al. (2013) | |
| c.41C>T | p.Ser14Leu | missense_variant | - | - | - | 17034946 | Feng J , et al. (2006) | |
| c.53T>A | p.Leu18Gln | missense_variant | - | - | - | 18179900 | Kim HG , et al. (2008) | |
| - | - | copy_number_loss | Familial | Maternal | - | 20531469 | Pinto D , et al. (2010) | |
| - | - | copy_number_loss | Familial | Paternal | - | 20531469 | Pinto D , et al. (2010) | |
| - | - | copy_number_loss | Familial | Paternal | - | 36309498 | Chan AJS et al. (2022) | |
| - | - | copy_number_loss | Unknown | Not maternal | - | 23533028 | Bna F , et al. (2013) | |
| c.105C>A | p.Gly35= | synonymous_variant | - | - | - | 18179900 | Kim HG , et al. (2008) | |
| - | - | copy_number_loss | Familial | Maternal | - | 21827697 | Gregor A , et al. (2011) | |
| - | - | copy_number_loss | Familial | Paternal | - | 21827697 | Gregor A , et al. (2011) | |
| - | - | copy_number_loss | Familial | Maternal | - | 32658356 | Alfieri P et al. (2020) | |
| - | - | copy_number_loss | Familial | Paternal | - | 32658356 | Alfieri P et al. (2020) | |
| - | - | copy_number_loss | De novo | - | Multiplex | 23294455 | Mller RS , et al. (2013) | |
| - | - | copy_number_loss | De novo | - | Simplex | 30675382 | Leblond CS , et al. (2019) | |
| c.912C>T | p.Gly304= | synonymous_variant | - | - | - | 18179900 | Kim HG , et al. (2008) | |
| - | - | copy_number_loss | Familial | Maternal | - | 22617343 | Schaaf CP , et al. (2012) | |
| - | - | copy_number_loss | Familial | Paternal | - | 22617343 | Schaaf CP , et al. (2012) | |
| - | - | copy_number_loss | Familial | Maternal | - | 23495017 | Dabell MP , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | - | 23495017 | Dabell MP , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | - | 31406558 | Munnich A , et al. (2019) | |
| - | - | copy_number_loss | De novo | - | Multiplex | 23495017 | Dabell MP , et al. (2013) | |
| - | - | copy_number_loss | Unknown | - | Multiplex | 23495017 | Dabell MP , et al. (2013) | |
| - | - | copy_number_loss | Unknown | - | Multiplex | 25149956 | Imitola J , et al. (2014) | |
| - | - | copy_number_loss | De novo | - | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| c.81A>G | p.(=) | synonymous_variant | Unknown | - | - | 22405623 | Liu Y , et al. (2012) | |
| c.1879+1G>A | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3484+1G>A | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2242C>A | p.Leu748Ile | missense_variant | - | - | - | 18179900 | Kim HG , et al. (2008) | |
| c.337C>T | p.Arg113Ter | stop_gained | De novo | - | - | 22914163 | Kong A , et al. (2012) | |
| c.3165C>T | p.Ala1055= | synonymous_variant | - | - | - | 18179900 | Kim HG , et al. (2008) | |
| c.3975C>T | p.Gly1325= | synonymous_variant | - | - | - | 18179900 | Kim HG , et al. (2008) | |
| c.4374A>G | p.Pro1458= | synonymous_variant | - | - | - | 18179900 | Kim HG , et al. (2008) | |
| - | - | copy_number_loss | Familial | Maternal | - | 30031152 | Al Shehhi M , et al. (2018) | |
| - | - | copy_number_loss | Familial | Paternal | - | 30031152 | Al Shehhi M , et al. (2018) | |
| - | - | copy_number_loss | De novo | - | Simplex | 25614873 | Vias-Jornet M , et al. (2015) | |
| - | - | copy_number_loss | De novo | - | - | 38739110 | Hamide Betul Gerik-Celebi et al. () | |
| c.4509C>G | p.Tyr1503Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 23533028 | Bna F , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 23533028 | Bna F , et al. (2013) | |
| - | - | copy_number_loss | Familial | Parental | Simplex | 23533600 | Nag A , et al. (2013) | |
| - | - | copy_number_loss | Unknown | Not maternal | - | 22617343 | Schaaf CP , et al. (2012) | |
| - | - | copy_number_loss | Unknown | - | Simplex | 23879678 | Walker S and Scherer SW (2013) | |
| - | - | copy_number_loss | Familial | Both parents | Simplex | 25486015 | Holmquist P (2014) | |
| c.132C>T | p.Pro44= | synonymous_variant | Unknown | - | - | 22405623 | Liu Y , et al. (2012) | |
| - | - | copy_number_loss | Familial | Paternal | Multiplex | 23533028 | Bna F , et al. (2013) | |
| - | - | copy_number_loss | De novo | - | Multi-generational | 23533600 | Nag A , et al. (2013) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 22337556 | Duong L , et al. (2012) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 33476483 | Cameli C et al. (2021) | |
| c.391G>A | p.Asp131Asn | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.705C>G | p.Ser235= | synonymous_variant | Unknown | - | - | 22405623 | Liu Y , et al. (2012) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 19896112 | Zweier C , et al. (2009) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 20468056 | Ching MS , et al. (2010) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 20468056 | Ching MS , et al. (2010) | |
| - | - | copy_number_loss | Familial | Maternal | Unknown | 23275889 | Prasad A , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Unknown | 23275889 | Prasad A , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 23294455 | Mller RS , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 32094338 | Husson T , et al. (2020) | |
| - | - | copy_number_loss | Familial | Paternal | - | 36660026 | Bentez-Burraco A et al. (2023) | |
| c.607A>T | p.Lys203Ter | stop_gained | Unknown | - | Unknown | 24126932 | Hu X , et al. (2013) | |
| c.972C>G | p.Tyr324Ter | stop_gained | Unknown | - | Unknown | 24126932 | Hu X , et al. (2013) | |
| c.1558G>C | p.Asp520His | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.1658C>T | p.Pro553Leu | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1851T>G | p.His617Gln | missense_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
| c.1873C>T | p.Arg625Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.1874G>A | p.Arg625Gln | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2222A>T | p.Asp741Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2267C>A | p.Ala756Glu | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2295G>A | p.Met765Ile | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2390C>T | p.Ala797Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2557C>T | p.Arg853Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2566C>T | p.Arg856Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2618G>A | p.Gly873Asp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2629G>C | p.Gly877Arg | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2684G>A | p.Arg895Gln | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.2959G>A | p.Gly987Arg | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3340G>A | p.Gly1114Arg | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3620G>A | p.Arg1207Gln | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4118C>T | p.Ser1373Phe | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4187C>T | p.Thr1396Met | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4295A>T | p.Asp1432Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4438G>A | p.Ala1480Thr | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.4363G>C | p.Glu1455Gln | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| - | - | copy_number_loss | Unknown | Not maternal | Multiplex | 23533028 | Bna F , et al. (2013) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 23294455 | Mller RS , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Multiplex | 23294455 | Mller RS , et al. (2013) | |
| c.83G>C | p.Gly28Ala | missense_variant | Unknown | - | - | 22892527 | Boccuto L , et al. (2012) | |
| - | - | copy_number_loss | Unknown | Not maternal | Simplex | 20468056 | Ching MS , et al. (2010) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 22617343 | Schaaf CP , et al. (2012) | |
| - | - | copy_number_loss | Familial | Paternal | Multiplex | 22617343 | Schaaf CP , et al. (2012) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 23495017 | Dabell MP , et al. (2013) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 30031152 | Al Shehhi M , et al. (2018) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 30031152 | Al Shehhi M , et al. (2018) | |
| c.4509C>G | p.Tyr1503Ter | stop_gained | Unknown | - | Simplex | 33004838 | Wang T et al. (2020) | |
| c.23G>C | p.Arg8Pro | missense_variant | Unknown | - | Unknown | 18490107 | Yan J , et al. (2008) | |
| - | - | copy_number_loss | Familial | Both parents | Simplex | 24508361 | Utine GE , et al. (2014) | |
| - | - | copy_number_loss | Familial | Paternal | Not simplex | 32094338 | Husson T , et al. (2020) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 21964664 | Harrison V , et al. (2011) | |
| - | - | copy_number_loss | Familial | Paternal | Multiplex | 21964664 | Harrison V , et al. (2011) | |
| c.-3G>T | - | 5_prime_UTR_variant | Familial | - | - | 22504536 | Camacho-Garcia RJ , et al. (2012) | |
| c.37C>T | p.Leu13Phe | missense_variant | Unknown | - | Unknown | 18490107 | Yan J , et al. (2008) | |
| c.83G>C | p.Gly28Ala | missense_variant | Unknown | - | Unknown | 18490107 | Yan J , et al. (2008) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 27018473 | Brandler WM , et al. (2016) | |
| - | - | copy_number_loss | Familial | Paternal | - | 38739110 | Hamide Betul Gerik-Celebi et al. () | |
| c.3485-11T>C | - | intron_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| - | - | copy_number_gain | Familial | Paternal | Simplex | 23879678 | Walker S and Scherer SW (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 23879678 | Walker S and Scherer SW (2013) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 25614873 | Vias-Jornet M , et al. (2015) | |
| c.2110G>A | p.Gly704Arg | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.925dup | p.Ser309LysfsTer2 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1994C>T | p.Thr665Ile | missense_variant | Unknown | - | Unknown | 18490107 | Yan J , et al. (2008) | |
| c.2143G>A | p.Glu715Lys | missense_variant | Unknown | - | Unknown | 18490107 | Yan J , et al. (2008) | |
| c.64G>C | p.Gly22Arg | missense_variant | De novo | - | Simplex | 29346770 | Takata A , et al. (2018) | |
| c.2865T>A | p.Tyr955Ter | stop_gained | De novo | - | Simplex | 22542183 | Iossifov I , et al. (2012) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 23879678 | Walker S and Scherer SW (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 28649445 | Woodbury-Smith M , et al. (2017) | |
| c.4237C>T | p.Pro1413Ser | missense_variant | Familial | Paternal | - | 37007974 | Hu C et al. (2023) | |
| c.4456C>A | p.Leu1486Ile | missense_variant | Familial | Maternal | - | 37007974 | Hu C et al. (2023) | |
| c.3333G>A | p.Met1111Ile | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
| c.844A>G | p.Ile282Val | missense_variant | Familial | Maternal | - | 22405623 | Liu Y , et al. (2012) | |
| c.412dup | p.Val138GlyfsTer49 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| - | - | copy_number_loss | Familial | Maternal or paternal | Simplex | 23533028 | Bna F , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal or maternal | Simplex | 23533028 | Bna F , et al. (2013) | |
| c.3572G>T | p.Arg1191Ile | missense_variant | Unknown | - | Simplex | 33004838 | Wang T et al. (2020) | |
| c.2687G>A | p.Arg896Gln | missense_variant | Unknown | - | Simplex | 37543562 | Sheth F et al. (2023) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 23207424 | Bermudez-Wagner K , et al. (2012) | |
| c.2677C>G | p.Leu893Val | missense_variant | Familial | Paternal | - | 22405623 | Liu Y , et al. (2012) | |
| c.664G>T | p.Glu222Ter | stop_gained | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.3403A>G | p.Ile1135Val | missense_variant | Familial | Paternal | - | 22405623 | Liu Y , et al. (2012) | |
| c.1025C>T | p.Thr342Ile | splice_site_variant | Unknown | - | Unknown | 18490107 | Yan J , et al. (2008) | |
| c.2573G>A | p.Gly858Glu | missense_variant | Familial | Maternal | - | 27824329 | Wang T , et al. (2016) | |
| c.2785G>A | p.Asp929Asn | missense_variant | Familial | Maternal | - | 27824329 | Wang T , et al. (2016) | |
| c.2785G>A | p.Asp929Asn | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
| c.2439_2446delinsC | p.Gly814Ter | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| c.3308C>T | p.Pro1103Leu | missense_variant | Familial | Maternal | - | 27824329 | Wang T , et al. (2016) | |
| - | - | complex_structural_alteration | Familial | Paternal | Simplex | 27841880 | Redin C , et al. (2016) | |
| c.2558G>A | p.Arg853His | missense_variant | De novo | - | Simplex | 25418537 | O'Roak BJ , et al. (2014) | |
| c.2210C>T | p.Thr737Met | missense_variant | Unknown | - | Unknown | 32942984 | Ishizuka K et al. (2020) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 23505263 | Van Den Bossche MJ , et al. (2013) | |
| c.3484+1G>T | - | splice_site_variant | Familial | Maternal | Simplex | 36309498 | Chan AJS et al. (2022) | |
| c.3490G>A | p.Val1164Ile | missense_variant | Unknown | - | Unknown | 32942984 | Ishizuka K et al. (2020) | |
| c.3595G>A | p.Ala1199Thr | missense_variant | Unknown | - | Unknown | 32942984 | Ishizuka K et al. (2020) | |
| c.3640G>A | p.Val1214Ile | missense_variant | Unknown | - | Unknown | 32942984 | Ishizuka K et al. (2020) | |
| c.3715G>A | p.Ala1239Thr | missense_variant | Unknown | - | Unknown | 32942984 | Ishizuka K et al. (2020) | |
| c.455G>A | p.Gly152Asp | missense_variant | Unknown | - | Unknown | 24066114 | Koshimizu E , et al. (2013) | |
| c.302C>T | p.Ala101Val | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.859A>C | p.Lys287Gln | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.1174A>C | p.Asn392His | missense_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2166G>T | p.Gln722His | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2725C>A | p.Leu909Met | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2804T>G | p.Leu935Arg | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2884C>G | p.Gln962Glu | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| - | - | copy_number_loss | Familial | Maternal | Extended multiplex | 30031152 | Al Shehhi M , et al. (2018) | |
| c.3G>T | p.Met1? | initiator_codon_variant | Familial | - | - | 22504536 | Camacho-Garcia RJ , et al. (2012) | |
| c.190C>T | p.Arg64Cys | missense_variant | Unknown | - | - | 38739110 | Hamide Betul Gerik-Celebi et al. () | |
| c.41C>T | p.Ser14Leu | missense_variant | Familial | Paternal | Simplex | 28289584 | Onay H , et al. (2017) | |
| c.2936C>G | p.Ser979Ter | stop_gained | Familial | Paternal | Simplex | 19896112 | Zweier C , et al. (2009) | |
| c.28G>A | p.Gly10Ser | missense_variant | - | Both parents | Multiplex | 31130284 | Monies D , et al. (2019) | |
| c.3763G>A | p.Val1255Ile | missense_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.3060_3063del | p.Lys1021LeufsTer10 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
| - | - | copy_number_loss | 4 de novo, 8 inherited, 18 unknown | - | Unknown | 25217958 | Coe BP , et al. (2014) | |
| c.118T>A | p.Trp40Arg | missense_variant | Familial | Maternal | Simplex | 17034946 | Feng J , et al. (2006) | |
| ins(ACGG) | p.Gly1402AspfsTer29 | frameshift_variant | De novo | - | - | 20797689 | Awadalla P , et al. (2010) | |
| - | - | copy_number_loss | Familial | Maternal | Extended multiplex | 25614873 | Vias-Jornet M , et al. (2015) | |
| - | - | copy_number_gain | Familial | Maternal | Multiplex | 20162629 | Winiowiecka-Kowalnik B , et al. (2010) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 20162629 | Winiowiecka-Kowalnik B , et al. (2010) | |
| c.2354G>A | p.Arg785Gln | missense_variant | Familial | Maternal | Simplex | 30564305 | Guo H , et al. (2018) | |
| c.41C>T | p.Ser14Leu | missense_variant | Familial | Paternal | Multiplex | 17034946 | Feng J , et al. (2006) | |
| c.1540G>T | p.Glu514Ter | stop_gained | Familial | Paternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| - | - | copy_number_gain | Unknown | Not maternal | Simplex | 20162629 | Winiowiecka-Kowalnik B , et al. (2010) | |
| - | - | copy_number_loss | De novo | - | Multiplex | 17322880 | Autism Genome Project Consortium , et al. (2007) | |
| c.2242C>A | p.Leu748Ile | missense_variant | Familial | Paternal | Simplex | 28289584 | Onay H , et al. (2017) | |
| c.471dup | p.Leu158AlafsTer29 | frameshift_variant | De novo | - | Simplex | 32094338 | Husson T , et al. (2020) | |
| c.931+1G>T | - | splice_site_variant | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.3018del | p.Phe1006LeufsTer26 | frameshift_variant | Familial | Maternal | - | 27824329 | Wang T , et al. (2016) | |
| c.2210C>T | p.Thr737Met | missense_variant | Familial | Maternal | Simplex | 32942984 | Ishizuka K et al. (2020) | |
| c.2315A>G | p.Asp772Gly | missense_variant | Familial | Maternal | Simplex | 32942984 | Ishizuka K et al. (2020) | |
| c.2566C>T | p.Arg856Trp | missense_variant | Familial | Maternal | Simplex | 32942984 | Ishizuka K et al. (2020) | |
| c.1945C>T | p.Leu649= | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2653C>T | p.His885Tyr | missense_variant | Familial | Paternal | Multiplex | 23849776 | Jiang YH , et al. (2013) | |
| c.308C>T | p.Thr103Ile | missense_variant | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2489del | p.Asn830IlefsTer25 | frameshift_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2879C>T | p.Thr960Ile | splice_site_variant | Familial | Paternal | Multiplex | 22337556 | Duong L , et al. (2012) | |
| c.4166del | p.Thr1389AsnfsTer57 | frameshift_variant | De novo | - | Simplex | 28191889 | Stessman HA , et al. (2017) | |
| c.4146_4147insGTCC | p.Met1383ValfsTer20 | frameshift_variant | De novo | - | - | 21424692 | Gauthier J , et al. (2011) | |
| c.1691A>G | p.Arg564Gly | missense_variant | Familial | Paternal | Multiplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.4311del | p.Cys1438ValfsTer8 | frameshift_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
| c.1679C>T | p.Thr560Ile | missense_variant | Familial | Maternal | - | 38739110 | Hamide Betul Gerik-Celebi et al. () | |
| c.1285del | p.Ile429TyrfsTer60 | frameshift_variant | Familial | Maternal | Simplex | 32094338 | Husson T , et al. (2020) | |
| c.1132G>A | p.Gly378Ser | missense_variant | Familial | Maternal | Simplex | 22504536 | Camacho-Garcia RJ , et al. (2012) | |
| c.1124G>A | p.Arg375Gln | missense_variant | Familial | Maternal | Multiplex | 22504536 | Camacho-Garcia RJ , et al. (2012) | |
| c.611T>A | p.Leu204Gln | missense_variant | Familial | Both parents | Multiplex | 33739554 | Taà Ÿkñran EZ et al. (2021) | |
| c.77_79dup | p.Glu26_Leu27insGln | inframe_insertion | Unknown | - | - | 38003033 | Ana Karen Sandoval-Talamantes et al. (2023) | |
| c.2437C>T | p.Arg813Cys | missense_variant | Familial | Paternal | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) |
Common Variants (5)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.999C>T;c.900C>T;c.840C>T;c.105C>T | p.(=) | synonymous_variant | - | - | - | 18179900 | Kim HG , et al. (2008) | |
| - | - | intron_variant | - | - | - | 38821058 | Yi Yang et al. () | |
| c.511C>T | p.(=) | synonymous_variant | - | - | - | 18179900 | Kim HG , et al. (2008) | |
| c.*110G>A | - | 3_prime_UTR_variant | - | - | - | 21687627 | Voineskos AN , et al. (2011) | |
| c.999C>T;c.900C>T;c.840C>T;c.105C>T | p.(=) | synonymous_variant | - | - | - | 22405623 | Liu Y , et al. (2012) |
SFARI Gene score
High Confidence
Score Delta: Score remained at 1
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
4/1/2021
Score remained at 1
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Integrated Transmission and De Novo Association (TADA) analysis of small de novo deletions and exome mutations from the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project identified NRXN1 as a ASD risk gene with a false discovery rate (FDR) 0.01 (Sanders et al., 2015). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome in which a significant number of affected individuals present with autistic features and/or motor stereotypies (Zweier et al., 2009; Harrison et al., 2011; Castronovo et al., 2019). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
1/1/2021
Score remained at 1
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Integrated Transmission and De Novo Association (TADA) analysis of small de novo deletions and exome mutations from the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project identified NRXN1 as a ASD risk gene with a false discovery rate (FDR) 0.01 (Sanders et al., 2015). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome in which a significant number of affected individuals present with autistic features and/or motor stereotypies (Zweier et al., 2009; Harrison et al., 2011; Castronovo et al., 2019). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
10/1/2020
Score remained at 1
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Integrated Transmission and De Novo Association (TADA) analysis of small de novo deletions and exome mutations from the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project identified NRXN1 as a ASD risk gene with a false discovery rate (FDR) 0.01 (Sanders et al., 2015). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome in which a significant number of affected individuals present with autistic features and/or motor stereotypies (Zweier et al., 2009; Harrison et al., 2011; Castronovo et al., 2019). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
7/1/2020
Score remained at 1
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Integrated Transmission and De Novo Association (TADA) analysis of small de novo deletions and exome mutations from the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project identified NRXN1 as a ASD risk gene with a false discovery rate (FDR) 0.01 (Sanders et al., 2015). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome in which a significant number of affected individuals present with autistic features and/or motor stereotypies (Zweier et al., 2009; Harrison et al., 2011; Castronovo et al., 2019). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
1/1/2020
Score remained at 1
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Integrated Transmission and De Novo Association (TADA) analysis of small de novo deletions and exome mutations from the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project identified NRXN1 as a ASD risk gene with a false discovery rate (FDR) 0.01 (Sanders et al., 2015). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome in which a significant number of affected individuals present with autistic features and/or motor stereotypies (Zweier et al., 2009; Harrison et al., 2011; Castronovo et al., 2019). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
Reports Added
[Increased Ca2+ signaling in NRXN1 +/- neurons derived from ASD induced pluripotent stem cells.2020] [The clinical relevance of intragenic NRXN1 deletions.2020] [Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020] [Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use.2020]10/1/2019
Decreased from 2 to 1
New Scoring Scheme
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Integrated Transmission and De Novo Association (TADA) analysis of small de novo deletions and exome mutations from the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project identified NRXN1 as a ASD risk gene with a false discovery rate (FDR) 0.01 (Sanders et al., 2015). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome in which a significant number of affected individuals present with autistic features and/or motor stereotypies (Zweier et al., 2009; Harrison et al., 2011; Castronovo et al., 2019). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
7/1/2019
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Integrated Transmission and De Novo Association (TADA) analysis of small de novo deletions and exome mutations from the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project identified NRXN1 as a ASD risk gene with a false discovery rate (FDR) 0.01 (Sanders et al., 2015). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome in which a significant number of affected individuals present with autistic features and/or motor stereotypies (Zweier et al., 2009; Harrison et al., 2011; Castronovo et al., 2019). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
Reports Added
[Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019] [Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019] [Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.2019]4/1/2019
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
1/1/2019
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
10/1/2018
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
7/1/2018
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
10/1/2017
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
7/1/2017
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD [9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016]. Multiple studies have also reported point mutations in NRXN1 in individuals with ASD (Feng et al., 17034946; Kim et al., 2008; Yan et al., 2008; Duong et al., 2012; Liu et al., 2012; Camacho-Garcia et al., 2012), including de novo loss-of-function variants in two probands from simplex families (Iossifov et al., 2012; Stessman et al., 2017). Biallelic mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011). A polymorphism located in the 3' UTR of NRXN1 was found to influence white matter volume and sensorimotor function in a cohort of healthy individuals in Voineskos et al., 2011 (PMID 21687627).
4/1/2017
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD (9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016). Mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011).
Reports Added
[High frequency of neurexin 1beta signal peptide structural variants in patients with autism.2006] [Mapping autism risk loci using genetic linkage and chromosomal rearrangements.2007] [Disruption of neurexin 1 associated with autism spectrum disorder.2008] [Neurexin 1alpha structural variants associated with autism.2008] [Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments.2009] [Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay.2010] [Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.2010] [Functional impact of global rare copy number variation in autism spectrum disorders.2010] [Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders.2011] [De novo gene disruptions in children on the autistic spectrum.2012] [Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Identification of candidate intergenic risk loci in autism spectrum disorder.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014] [Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions.2012] [Rate of de novo mutations and the importance of father's age to disease risk.2012] [Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders.2012] [Mutation analysis of the NRXN1 gene in a Chinese autism cohort.2012] [Mutations affecting synaptic levels of neurexin-1 in autism and mental retardation.2012] [2p16.3 microdeletion with partial deletion of the neurexin-1 gene in a female with developmental delays, short stature, and a congenital diaphragma...2012] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Investigation of NRXN1 deletions: clinical and molecular characterization.2013] [Etiological yield of SNP microarrays in idiopathic intellectual disability.2014] [Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy.2013] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [A boy with dysmorphic features, intellectual disability, and biallelic homozygous deletion in NRXN1.2014] [A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion.2015] [Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.2013] [A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha.2007] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Compound heterozygous deletion of NRXN1 causing severe developmental delay with early onset epilepsy in two sisters.2011] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Fraternal twins with autism, severe cognitive deficit, and epilepsy: diagnostic role of chromosomal microarray analysis.2014] [Recurrent CNVs disrupt three candidate genes in schizophrenia patients.2008] [Disruption of the neurexin 1 gene is associated with schizophrenia.2008] [Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.2010] [Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia.2011] [Identification of rare copy number variants in high burden schizophrenia families.2013] [A survey of rare coding variants in candidate genes in schizophrenia by deep sequencing.2013] [CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.2013] [Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules.1997] [Neurexin mediates the assembly of presynaptic terminals.2003] [Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex.2006] [Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95-neuroligin.2007] [Silencing of neuroligin function by postsynaptic neurexins.2007] [Presynaptic targeting of alpha4beta 2 nicotinic acetylcholine receptors is regulated by neurexin-1beta.2009] [Sensory regulation of neuroligins and neurexin I in the honeybee brain.2010] [Neurexins physically and functionally interact with GABA(A) receptors.2010] [Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum.2010] [Splice form dependence of beta-neurexin/neuroligin binding interactions.2010] [Modeling the functional genomics of autism using human neurons.2011] [Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1 and activation of fibroblast growth factor receptor-1.2012] [Neurexin regulates visual function via mediating retinoid transport to promote rhodopsin maturation.2013] [Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models.2013] [Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins.2014] [Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Frequency and Complexity of De Novo Structural Mutation in Autism.2016] [Molecular characterization of NRXN1 deletions from 19,263 clinical microarray cases identifies exons important for neurodevelopmental disease expre...2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017] [Mutation analysis of the NRXN1 gene in autism spectrum disorders.2017]1/1/2017
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD (9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016). Mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011).
10/1/2016
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD (9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016). Mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011).
4/1/2016
Decreased from 2 to 2
Description
Numerous studies have demonstrated a statistically significant enrichment of NRXN1 deletions in ASD cases compared to controls [10 in 2195 cases vs. none in 2519 controls (permuted P-value 0.002) in Glessner et al., 2009; 9 in 1771 cases vs. none in 2539 controls (P-value 3.3 E-04) in Bucan et al., 2009; an excess of exonic NRNX1 CNVs in 996 cases compared to 4,964 controls ((P-value 7.7E-4) in Pinto et al., 2010; 7 exonic deletions in 2,588 cases vs. 1 in 2,670 controls (P-value 0.032) in Girirajan et al., 2013]. A similar enrichment of NRXN1 deletions have been repeatedly observed in cohorts composed of cases with a spectrum of neurodevelopmental disorders, including ASD (9 exonic NRXN1 deletions in 3,540 cases vs. 10 in 51,939 controls (P-value 8.9E-07) in Ching et al., 2010; exonic NRXN1 deletions observed in 0.11% of cases compared to 0.02% of controls (P-value 6.08E-07) in Dabell et al., 2013; NRXN1 deletions in 30 cases vs. 9 controls (simulated P-value of 0.00005) in Coe et al., 2014; P<0.0001 in 19,263 cases and 15,264 controls in Lowther et al., 2016). Mutations in NRXN1 have also been implicated in Pitt-Hopkins-like syndrome 2, an autosomal recessive intellectual disability syndrome (Zweier et al., 2009; Harrison et al., 2011).
Reports Added
[High frequency of neurexin 1beta signal peptide structural variants in patients with autism.2006] [Mapping autism risk loci using genetic linkage and chromosomal rearrangements.2007] [Disruption of neurexin 1 associated with autism spectrum disorder.2008] [Neurexin 1alpha structural variants associated with autism.2008] [Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments.2009] [Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay.2010] [Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.2010] [Functional impact of global rare copy number variation in autism spectrum disorders.2010] [Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders.2011] [De novo gene disruptions in children on the autistic spectrum.2012] [Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Identification of candidate intergenic risk loci in autism spectrum disorder.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014] [Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions.2012] [Rate of de novo mutations and the importance of father's age to disease risk.2012] [Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders.2012] [Mutation analysis of the NRXN1 gene in a Chinese autism cohort.2012] [Mutations affecting synaptic levels of neurexin-1 in autism and mental retardation.2012] [2p16.3 microdeletion with partial deletion of the neurexin-1 gene in a female with developmental delays, short stature, and a congenital diaphragma...2012] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Investigation of NRXN1 deletions: clinical and molecular characterization.2013] [Etiological yield of SNP microarrays in idiopathic intellectual disability.2014] [Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy.2013] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [A boy with dysmorphic features, intellectual disability, and biallelic homozygous deletion in NRXN1.2014] [A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion.2015] [Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.2013] [A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha.2007] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Compound heterozygous deletion of NRXN1 causing severe developmental delay with early onset epilepsy in two sisters.2011] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Fraternal twins with autism, severe cognitive deficit, and epilepsy: diagnostic role of chromosomal microarray analysis.2014] [Recurrent CNVs disrupt three candidate genes in schizophrenia patients.2008] [Disruption of the neurexin 1 gene is associated with schizophrenia.2008] [Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.2010] [Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia.2011] [Identification of rare copy number variants in high burden schizophrenia families.2013] [A survey of rare coding variants in candidate genes in schizophrenia by deep sequencing.2013] [CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.2013] [Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules.1997] [Neurexin mediates the assembly of presynaptic terminals.2003] [Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex.2006] [Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95-neuroligin.2007] [Silencing of neuroligin function by postsynaptic neurexins.2007] [Presynaptic targeting of alpha4beta 2 nicotinic acetylcholine receptors is regulated by neurexin-1beta.2009] [Sensory regulation of neuroligins and neurexin I in the honeybee brain.2010] [Neurexins physically and functionally interact with GABA(A) receptors.2010] [Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum.2010] [Splice form dependence of beta-neurexin/neuroligin binding interactions.2010] [Modeling the functional genomics of autism using human neurons.2011] [Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1 and activation of fibroblast growth factor receptor-1.2012] [Neurexin regulates visual function via mediating retinoid transport to promote rhodopsin maturation.2013] [Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models.2013] [Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins.2014] [Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Frequency and Complexity of De Novo Structural Mutation in Autism.2016] [Molecular characterization of NRXN1 deletions from 19,263 clinical microarray cases identifies exons important for neurodevelopmental disease expre...2016]1/1/2016
Decreased from 2 to 2
Description
Ching et al. provide results that approach genome-wide significant criteria (8 x 10-7), with 12/3450 cases observed to carry deletions as compared to 0 controls obtained from other work. A similar range of outcomes is observed amongst cases including autism spectrum disorders, mental retardation, language delays, and hypotonia. The sample overlap with Bucan et al. is unclear, but similar results are reported, with exonic deletions in 9 of ~2000 cases versus 0 / ~ 2500 controls. Zweier et al. show that an individual with autosomal-recessive Pitt-Hopkins-like mental retardation is a carrier for two heterozygous variants argued to be pathogenic.
Reports Added
[High frequency of neurexin 1beta signal peptide structural variants in patients with autism.2006] [Mapping autism risk loci using genetic linkage and chromosomal rearrangements.2007] [Disruption of neurexin 1 associated with autism spectrum disorder.2008] [Neurexin 1alpha structural variants associated with autism.2008] [Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments.2009] [Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay.2010] [Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.2010] [Functional impact of global rare copy number variation in autism spectrum disorders.2010] [Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders.2011] [De novo gene disruptions in children on the autistic spectrum.2012] [Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Identification of candidate intergenic risk loci in autism spectrum disorder.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014] [Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions.2012] [Rate of de novo mutations and the importance of father's age to disease risk.2012] [Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders.2012] [Mutation analysis of the NRXN1 gene in a Chinese autism cohort.2012] [Mutations affecting synaptic levels of neurexin-1 in autism and mental retardation.2012] [2p16.3 microdeletion with partial deletion of the neurexin-1 gene in a female with developmental delays, short stature, and a congenital diaphragma...2012] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Investigation of NRXN1 deletions: clinical and molecular characterization.2013] [Etiological yield of SNP microarrays in idiopathic intellectual disability.2014] [Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy.2013] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [A boy with dysmorphic features, intellectual disability, and biallelic homozygous deletion in NRXN1.2014] [A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion.2015] [Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.2013] [A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha.2007] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Compound heterozygous deletion of NRXN1 causing severe developmental delay with early onset epilepsy in two sisters.2011] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Fraternal twins with autism, severe cognitive deficit, and epilepsy: diagnostic role of chromosomal microarray analysis.2014] [Recurrent CNVs disrupt three candidate genes in schizophrenia patients.2008] [Disruption of the neurexin 1 gene is associated with schizophrenia.2008] [Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.2010] [Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia.2011] [Identification of rare copy number variants in high burden schizophrenia families.2013] [A survey of rare coding variants in candidate genes in schizophrenia by deep sequencing.2013] [CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.2013] [Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules.1997] [Neurexin mediates the assembly of presynaptic terminals.2003] [Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex.2006] [Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95-neuroligin.2007] [Silencing of neuroligin function by postsynaptic neurexins.2007] [Presynaptic targeting of alpha4beta 2 nicotinic acetylcholine receptors is regulated by neurexin-1beta.2009] [Sensory regulation of neuroligins and neurexin I in the honeybee brain.2010] [Neurexins physically and functionally interact with GABA(A) receptors.2010] [Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum.2010] [Splice form dependence of beta-neurexin/neuroligin binding interactions.2010] [Modeling the functional genomics of autism using human neurons.2011] [Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1 and activation of fibroblast growth factor receptor-1.2012] [Neurexin regulates visual function via mediating retinoid transport to promote rhodopsin maturation.2013] [Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models.2013] [Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins.2014] [Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015]7/1/2015
Decreased from 2 to 2
Description
Ching et al. provide results that approach genome-wide significant criteria (8 x 10-7), with 12/3450 cases observed to carry deletions as compared to 0 controls obtained from other work. A similar range of outcomes is observed amongst cases including autism spectrum disorders, mental retardation, language delays, and hypotonia. The sample overlap with Bucan et al. is unclear, but similar results are reported, with exonic deletions in 9 of ~2000 cases versus 0 / ~ 2500 controls. Zweier et al. show that an individual with autosomal-recessive Pitt-Hopkins-like mental retardation is a carrier for two heterozygous variants argued to be pathogenic.
Reports Added
[High frequency of neurexin 1beta signal peptide structural variants in patients with autism.2006] [Mapping autism risk loci using genetic linkage and chromosomal rearrangements.2007] [Disruption of neurexin 1 associated with autism spectrum disorder.2008] [Neurexin 1alpha structural variants associated with autism.2008] [Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments.2009] [Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay.2010] [Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.2010] [Functional impact of global rare copy number variation in autism spectrum disorders.2010] [Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders.2011] [De novo gene disruptions in children on the autistic spectrum.2012] [Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Identification of candidate intergenic risk loci in autism spectrum disorder.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014] [Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions.2012] [Rate of de novo mutations and the importance of father's age to disease risk.2012] [Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders.2012] [Mutation analysis of the NRXN1 gene in a Chinese autism cohort.2012] [Mutations affecting synaptic levels of neurexin-1 in autism and mental retardation.2012] [2p16.3 microdeletion with partial deletion of the neurexin-1 gene in a female with developmental delays, short stature, and a congenital diaphragma...2012] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Investigation of NRXN1 deletions: clinical and molecular characterization.2013] [Etiological yield of SNP microarrays in idiopathic intellectual disability.2014] [Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy.2013] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [A boy with dysmorphic features, intellectual disability, and biallelic homozygous deletion in NRXN1.2014] [A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion.2015] [Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.2013] [A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha.2007] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Compound heterozygous deletion of NRXN1 causing severe developmental delay with early onset epilepsy in two sisters.2011] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Fraternal twins with autism, severe cognitive deficit, and epilepsy: diagnostic role of chromosomal microarray analysis.2014] [Recurrent CNVs disrupt three candidate genes in schizophrenia patients.2008] [Disruption of the neurexin 1 gene is associated with schizophrenia.2008] [Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.2010] [Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia.2011] [Identification of rare copy number variants in high burden schizophrenia families.2013] [A survey of rare coding variants in candidate genes in schizophrenia by deep sequencing.2013] [CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.2013] [Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules.1997] [Neurexin mediates the assembly of presynaptic terminals.2003] [Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex.2006] [Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95-neuroligin.2007] [Silencing of neuroligin function by postsynaptic neurexins.2007] [Presynaptic targeting of alpha4beta 2 nicotinic acetylcholine receptors is regulated by neurexin-1beta.2009] [Sensory regulation of neuroligins and neurexin I in the honeybee brain.2010] [Neurexins physically and functionally interact with GABA(A) receptors.2010] [Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum.2010] [Splice form dependence of beta-neurexin/neuroligin binding interactions.2010] [Modeling the functional genomics of autism using human neurons.2011] [Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1 and activation of fibroblast growth factor receptor-1.2012] [Neurexin regulates visual function via mediating retinoid transport to promote rhodopsin maturation.2013] [Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models.2013] [Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins.2014] [Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging.2015] [Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.2015]1/1/2015
Decreased from 2 to 2
Description
Ching et al. provide results that approach genome-wide significant criteria (8 x 10-7), with 12/3450 cases observed to carry deletions as compared to 0 controls obtained from other work. A similar range of outcomes is observed amongst cases including autism spectrum disorders, mental retardation, language delays, and hypotonia. The sample overlap with Bucan et al. is unclear, but similar results are reported, with exonic deletions in 9 of ~2000 cases versus 0 / ~ 2500 controls. Zweier et al. show that an individual with autosomal-recessive Pitt-Hopkins-like mental retardation is a carrier for two heterozygous variants argued to be pathogenic.
10/1/2014
Decreased from 2 to 2
Description
Ching et al. provide results that approach genome-wide significant criteria (8 x 10-7), with 12/3450 cases observed to carry deletions as compared to 0 controls obtained from other work. A similar range of outcomes is observed amongst cases including autism spectrum disorders, mental retardation, language delays, and hypotonia. The sample overlap with Bucan et al. is unclear, but similar results are reported, with exonic deletions in 9 of ~2000 cases versus 0 / ~ 2500 controls. Zweier et al. show that an individual with autosomal-recessive Pitt-Hopkins-like mental retardation is a carrier for two heterozygous variants argued to be pathogenic.
Reports Added
[Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014] [Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014]7/1/2014
Increased from No data to 2
Description
Ching et al. provide results that approach genome-wide significant criteria (8 x 10-7), with 12/3450 cases observed to carry deletions as compared to 0 controls obtained from other work. A similar range of outcomes is observed amongst cases including autism spectrum disorders, mental retardation, language delays, and hypotonia. The sample overlap with Bucan et al. is unclear, but similar results are reported, with exonic deletions in 9 of ~2000 cases versus 0 / ~ 2500 controls. Zweier et al. show that an individual with autosomal-recessive Pitt-Hopkins-like mental retardation is a carrier for two heterozygous variants argued to be pathogenic.
Reports Added
[Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules.1997] [Neurexin mediates the assembly of presynaptic terminals.2003] [Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex.2006] [High frequency of neurexin 1beta signal peptide structural variants in patients with autism.2006] [Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95-neuroligin.2007] [Mapping autism risk loci using genetic linkage and chromosomal rearrangements.2007] [Silencing of neuroligin function by postsynaptic neurexins.2007] [A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha.2007] [Disruption of neurexin 1 associated with autism spectrum disorder.2008] [Neurexin 1alpha structural variants associated with autism.2008] [Recurrent CNVs disrupt three candidate genes in schizophrenia patients.2008] [Disruption of the neurexin 1 gene is associated with schizophrenia.2008] [Presynaptic targeting of alpha4beta 2 nicotinic acetylcholine receptors is regulated by neurexin-1beta.2009] [Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments.2009] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Sensory regulation of neuroligins and neurexin I in the honeybee brain.2010] [Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay.2010] [Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.2010] [Neurexins physically and functionally interact with GABA(A) receptors.2010] [Functional impact of global rare copy number variation in autism spectrum disorders.2010] [Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum.2010] [Splice form dependence of beta-neurexin/neuroligin binding interactions.2010] [Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.2010] [Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia.2011] [Modeling the functional genomics of autism using human neurons.2011] [Neurexin-1 and frontal lobe white matter: an overlapping intermediate phenotype for schizophrenia and autism spectrum disorders.2011] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [Compound heterozygous deletion of NRXN1 causing severe developmental delay with early onset epilepsy in two sisters.2011] [Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders.2012] [Mutation analysis of the NRXN1 gene in a Chinese autism cohort.2012] [Mutations affecting synaptic levels of neurexin-1 in autism and mental retardation.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions.2012] [Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1 and activation of fibroblast growth factor receptor-1.2012] [Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion.2012] [Rate of de novo mutations and the importance of father's age to disease risk.2012] [2p16.3 microdeletion with partial deletion of the neurexin-1 gene in a female with developmental delays, short stature, and a congenital diaphragma...2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy.2013] [Neurexin regulates visual function via mediating retinoid transport to promote rhodopsin maturation.2013] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Investigation of NRXN1 deletions: clinical and molecular characterization.2013] [Identification of rare copy number variants in high burden schizophrenia families.2013] [Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.2013] [CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.2013] [Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Identification of candidate intergenic risk loci in autism spectrum disorder.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [A survey of rare coding variants in candidate genes in schizophrenia by deep sequencing.2013] [Etiological yield of SNP microarrays in idiopathic intellectual disability.2014] [Fraternal twins with autism, severe cognitive deficit, and epilepsy: diagnostic role of chromosomal microarray analysis.2014]4/1/2014
Increased from No data to 2
Description
Ching et al. provide results that approach genome-wide significant criteria (8 x 10-7), with 12/3450 cases observed to carry deletions as compared to 0 controls obtained from other work. A similar range of outcomes is observed amongst cases including autism spectrum disorders, mental retardation, language delays, and hypotonia. The sample overlap with Bucan et al. is unclear, but similar results are reported, with exonic deletions in 9 of ~2000 cases versus 0 / ~ 2500 controls. Zweier et al. show that an individual with autosomal-recessive Pitt-Hopkins-like mental retardation is a carrier for two heterozygous variants argued to be pathogenic.
Krishnan Probability Score
Score 0.93000000000001
Ranking 2/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.9999487383563
Ranking 587/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.946
Ranking 86/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 2.3114044581107E-7
Ranking 4/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 132
Ranking 5/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.4059312435315
Ranking 1391/20870 scored genes
[Show Scoring Methodology]
CNVs associated with NRXN1(1 CNVs)
Sort By:
| 2p16.3 | 88 | Deletion-Duplication | 131 / 545 |
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| Abpa2 | amyloid beta (A4) precursor protein-binding, family A, member 2 | Rat | Protein Binding | 83610 | O35431 |
| Chadl | chondroadherin-like | Mouse | Protein Binding | 214685 | E9Q7T7 |
| Lrrtm1 | leucine rich repeat transmembrane neuronal 1 | Mouse | Protein Binding | 74342 | Q8K377 |
| Nlgn4l | neuroligin 4-like | Mouse | Protein Binding | 100113365 | B0F2B4 |
| Nxph1 | neurexophilin 1 | Rat | Protein Binding | 25501 | Q63366 |
| Nxph3 | neurexophilin 3 | Rat | Protein Binding | 59315 | Q9Z2N5 |
| SDCBP2 | syndecan binding protein (syntenin) 2 | Human | Protein Binding | 27111 | Q9H190 |
| Spon1 | spondin 1, (f-spondin) extracellular matrix protein | Mouse | Protein Binding | 233744 | Q8VCC9 |
| Syt2 | synaptotagmin II | Rat | Protein Binding | 24805 | P29101 |
| Syt6 | synaptotagmin VI | Rat | Protein Binding | 60565 | Q62746 |
| Sytl1 | synaptotagmin-like 1 | Mouse | Protein Binding | 269589 | Q99N80 |
| Sytl2 | synaptotagmin-like 2 | Mouse | Protein Binding | 83671 | Q99N50 |
| Sytl3 | synaptotagmin-like 3 | Mouse | Protein Binding | 83672 | Q99N48 |