Human Gene Module / Chromosome 7 / CNTNAP2

CNTNAP2contactin associated protein-like 2

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
54 / 96
Rare Variants / Common Variants
131 / 36
Aliases
CNTNAP2, CDFE,  NRXN4,  CASPR2,  DKFZp781D1846
Associated Syndromes
Cortical dysplasia-focal epilepsy syndrome, Pitt-Hopkins like syndrome 1, Pitt-Hopkins like syndrome 1, DD, epilepsy/seizure
Chromosome Band
7q35-q36.1
Associated Disorders
ADHD, ID, EP, BPD, EPS, ASD
Relevance to Autism

Several studies have found a genetic association of the CNTNAP2 gene with autism. Among these, one study (Li et al., 2010) found positive association with the Chinese Han population. In addition, rare variants in the CNTNAP2 gene, including deletions and nonsynonymous changes, are also suggested to play a role in autism, ID, DD and language impairment. Interestingly, positive associations with CNTNAP2 and selective mutism, epilepsy and specific language impairment have also been found.

Molecular Function

This gene encodes a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein is localized at the juxtaparanodes of myelinated axons and associated with potassium channels.

SFARI Genomic Platforms
Reports related to CNTNAP2 (96 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels Poliak S , et al. (2000) No -
2 Support CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder Verkerk AJ , et al. (2003) No TS, ID
3 Support Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2 Strauss KA , et al. (2006) No ID, ADHD, ASD, epilepsy/seizures
4 Support CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy Friedman JI , et al. (2007) No Epilepsy
5 Positive Association Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene Alarcn M , et al. (2008) Yes -
6 Primary A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism Arking DE , et al. (2008) Yes -
7 Support Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders Bakkaloglu B , et al. (2008) Yes -
8 Positive Association A functional genetic link between distinct developmental language disorders Vernes SC , et al. (2008) Yes -
9 Recent Recommendation Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons Horresh I , et al. (2008) No -
10 Recent Recommendation Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS Oiso S , et al. (2009) No -
11 Support Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder Poot M , et al. (2009) Yes -
12 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
13 Recent Recommendation Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B Horresh I , et al. (2010) No -
14 Recent Recommendation Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2 Tan GC , et al. (2010) No -
15 Positive Association Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population Li X , et al. (2010) Yes -
16 Recent Recommendation Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies Mefford HC , et al. (2010) No ASD
17 Recent Recommendation Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2 Scott-Van Zeeland AA , et al. (2010) No -
18 Support Identification of a microdeletion at the 7q33-q35 disrupting the CNTNAP2 gene in a Brazilian stuttering case Petrin AL , et al. (2010) Yes -
19 Recent Recommendation A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-related traits Stein MB , et al. (2011) No -
20 Positive Association CNTNAP2 variants affect early language development in the general population Whitehouse AJ , et al. (2011) Yes -
21 Support Reduced transcript expression of genes affected by inherited and de novo CNVs in autism Nord AS , et al. (2011) Yes -
22 Support Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations O'Roak BJ , et al. (2011) Yes -
23 Recent Recommendation Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1 Gregor A , et al. (2011) No -
24 Recent Recommendation Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits Peagarikano O , et al. (2011) No -
25 Recent Recommendation Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders Mikhail FM , et al. (2011) No ID
26 Support Rare copy number variants are an important cause of epileptic encephalopathies Mefford HC , et al. (2011) No ID, ASD
27 Support Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link with autism Lesca G , et al. (2012) No ADHD
28 Recent Recommendation Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization Laffin JJ , et al. (2012) No -
29 Positive Association Individual common variants exert weak effects on the risk for autism spectrum disorders Anney R , et al. (2012) Yes -
30 Recent Recommendation Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development Anderson GR , et al. (2012) No -
31 Support Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay Al-Murrani A , et al. (2012) No -
32 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
33 Negative Association Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2 Toma C , et al. (2013) Yes -
34 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder Girirajan S , et al. (2013) Yes -
35 Recent Recommendation CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study Clemm von Hohenberg C , et al. (2013) No -
36 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
37 Support Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech Worthey EA , et al. (2013) No -
38 Positive Association Defining the contribution of CNTNAP2 to autism susceptibility Sampath S , et al. (2013) Yes -
39 Support Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families Egger G , et al. (2014) Yes -
40 Support Diagnostic whole genome sequencing and split-read mapping for nucleotide resolution breakpoint identification in CNTNAP2 deficiency syndrome Watson CM , et al. (2014) No Epilepsy
41 Positive Association Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach Chiocchetti AG , et al. (2014) Yes -
42 Positive Association A candidate gene association study further corroborates involvement of contactin genes in autism Poot M (2014) Yes -
43 Negative Association No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins Murdoch JD , et al. (2015) Yes -
44 Support Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease Karaca E , et al. (2015) No Epilepsy/seizures
45 Negative Association CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches Werling AM , et al. (2015) Yes -
46 Recent Recommendation Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2 Hoffman EJ , et al. (2016) No -
47 Support Characterisation of CASPR2 deficiency disorder--a syndrome involving autism, epilepsy and language impairment Rodenas-Cuadrado P , et al. (2016) Yes -
48 Support Comprehensive molecular testing in patients with high functioning autism spectrum disorder Alvarez-Mora MI , et al. (2016) Yes -
49 Positive Association Single nucleotide polymorphisms in the CNTNAP2 gene in Brazilian patients with autistic spectrum disorder Nascimento PP , et al. (2016) Yes -
50 Support Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells Lee IS , et al. (2016) No -
51 Support Eight further individuals with intellectual disability and epilepsy carrying bi-allelic CNTNAP2 aberrations allow delineation of the mutational and phenotypic spectrum Smogavec M , et al. (2016) No -
52 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
53 Support Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes Parrini E , et al. (2016) No -
54 Support Associations between the CNTNAP2 gene, dorsolateral prefrontal cortex, and cognitive performance on the Stroop task Zhu B , et al. (2016) No -
55 Support Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment Chen XS , et al. (2017) No -
56 Support Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration Ross LA , et al. (2017) No -
57 Support Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
58 Support Genetic testing including targeted gene panel in a diverse clinical population of children with autism spectrum disorder: Findings and implications Kalsner L , et al. (2017) Yes -
59 Recent Recommendation Genetic variants in autism-related CNTNAP2 impair axonal growth of cortical neurons Canali G , et al. (2018) No -
60 Positive Association Genetic variants in the CNTNAP2 gene are associated with gender differences among dyslexic children in China Gu H , et al. (2018) No -
61 Negative Association Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders Toma C , et al. (2018) Yes BPD
62 Support Both rare and common genetic variants contribute to autism in the Faroe Islands Leblond CS , et al. (2019) Yes -
63 Negative Association Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS data of psychiatric genomics consortium Zhang T , et al. (2019) Yes -
64 Support Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations Zhou WZ , et al. (2019) Yes -
65 Support The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children Long S , et al. (2019) Yes -
66 Support Characterization of intellectual disability and autism comorbidity through gene panel sequencing Aspromonte MC , et al. (2019) Yes -
67 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
68 Support Genome-wide detection of tandem DNA repeats that are expanded in autism Trost B et al. (2020) Yes -
69 Support - Ohashi K et al. (2021) Yes -
70 Positive Association - Li D et al. (2021) No Gray matter volume and social performance
71 Positive Association - Uddin MS et al. (2021) Yes Language impairment
72 Positive Association - Fang F et al. (2021) Yes -
73 Support - Pode-Shakked B et al. (2021) Yes -
74 Support - Mitani T et al. (2021) No -
75 Support - Scala M et al. (2021) No Autistic features, stereotypy
76 Support - Mittal R et al. (2021) No ASD
77 Support - Shiota Y et al. (2021) Yes ASD subphenotypes
78 Support - Scott KE et al. (2022) No -
79 Support - Woodbury-Smith M et al. (2022) Yes -
80 Support - Lithuania) (04/0) Yes -
81 Positive Association - Shiota Y et al. (2022) Yes -
82 Support - Badshah N et al. (2022) No ASD, stereotypy
83 Support - Zhou X et al. (2022) Yes -
84 Support - Jang WE et al. (2022) Yes -
85 Support - Mhrle D et al. (2023) Yes -
86 Support - Cifuentes-Diaz C et al. (2023) No -
87 Recent Recommendation - Weinschutz Mendes H et al. (2023) Yes -
88 Support - Spataro N et al. (2023) Yes -
89 Support - Haddad FL et al. (2023) Yes -
90 Support - St George-Hyslop F et al. (2023) No -
91 Recent Recommendation - D&#x27 et al. (2023) No ASD, ADHD
92 Support - Zhang J et al. (2023) Yes -
93 Support - Cirnigliaro M et al. (2023) Yes -
94 Support - Sheth F et al. (2023) Yes DD, ID
95 Support - Dawson MS et al. (2023) Yes -
96 Support - et al. () Yes -
Rare Variants   (131)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 22031302 Mikhail FM , et al. (2011)
- - copy_number_loss Unknown - - 24643514 Egger G , et al. (2014)
- - copy_number_loss De novo - - 21827697 Gregor A , et al. (2011)
- - minisatellite Unknown - Simplex 32717741 Trost B et al. (2020)
- - minisatellite Unknown - Unknown 32717741 Trost B et al. (2020)
T>C - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
- - copy_number_gain Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_loss Familial Maternal - 21448237 Nord AS , et al. (2011)
c.2153G>A p.Trp718Ter stop_gained - - - 21827697 Gregor A , et al. (2011)
- - copy_number_loss Unknown - Simplex 21108403 Petrin AL , et al. (2010)
- - copy_number_loss Unknown - Simplex 22766611 Laffin JJ , et al. (2012)
- - copy_number_loss Familial Maternal - 21827697 Gregor A , et al. (2011)
- - copy_number_gain Familial Paternal Simplex 35454361 Lithuania) (04/0)
- - copy_number_loss Unknown - Simplex 17646849 Friedman JI , et al. (2007)
c.98-119906del - intron_variant - - Unknown 27667684 Doan RN , et al. (2016)
- - copy_number_loss Familial Paternal - 20502679 Mefford HC , et al. (2010)
- - copy_number_loss Familial Maternal Simplex 37183190 D&#x27 et al. (2023)
- - copy_number_loss Familial Paternal Simplex 37183190 D&#x27 et al. (2023)
c.1778-1G>C - splice_site_variant De novo - - 30763456 Zhou WZ , et al. (2019)
- - copy_number_loss Familial Paternal Simplex 26985448 Lee IS , et al. (2016)
- - copy_number_gain Familial Maternal Unknown 22738016 Lesca G , et al. (2012)
c.655T>A p.Ser219Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Maternal Simplex 19896112 Zweier C , et al. (2009)
- - copy_number_loss Familial Paternal Multiplex 34778490 Mittal R et al. (2021)
c.1220A>G p.Asn407Ser missense_variant - - - 18179895 Bakkaloglu B , et al. (2008)
c.1252A>G p.Asn418Asp missense_variant - - - 18179895 Bakkaloglu B , et al. (2008)
c.2147A>G p.Tyr716Cys missense_variant - - - 18179895 Bakkaloglu B , et al. (2008)
c.3862C>T p.Arg1288Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - complex_structural_alteration De novo - Simplex 19582487 Poot M , et al. (2009)
- - copy_number_loss Familial Paternal Multiplex 18179893 Alarcn M , et al. (2008)
c.3058C>T p.Gln1020Ter stop_gained De novo - - 31452935 Feliciano P et al. (2019)
- - copy_number_gain Familial Maternal Simplex 27439707 Smogavec M , et al. (2016)
- - copy_number_loss Familial Maternal Simplex 27439707 Smogavec M , et al. (2016)
- - copy_number_loss Familial Paternal Simplex 27439707 Smogavec M , et al. (2016)
- - copy_number_gain Familial Maternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Paternal Simplex 23375656 Girirajan S , et al. (2013)
c.1777+2T>C - splice_site_variant - Both parents - 27864847 Parrini E , et al. (2016)
- - copy_number_loss Familial Paternal Multiplex 27439707 Smogavec M , et al. (2016)
c.152C>G p.Ser51Cys missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
- - copy_number_loss Familial Both parents Multiplex 19896112 Zweier C , et al. (2009)
- - copy_number_loss Familial Both parents Multiplex 26539891 Karaca E , et al. (2015)
- - copy_number_loss Familial Maternal Multiplex 23074684 Al-Murrani A , et al. (2012)
c.653C>T p.Thr218Met missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.686_688del p.Glu229del inframe_deletion De novo - - 36980980 Spataro N et al. (2023)
c.1679C>G p.Pro560Arg missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.2396A>G p.Asn799Ser missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.2797T>C p.Phe933Leu missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
- - copy_number_loss Familial Both parents Multiplex 22190369 Mefford HC , et al. (2011)
c.3814A>T p.Ile1272Phe missense_variant De novo - Simplex 37183190 D&#x27 et al. (2023)
c.98-?_402+? - copy_number_loss Familial Maternal Simplex 37183190 D&#x27 et al. (2023)
c.1634C>T p.Ala545Val missense_variant De novo - Simplex 37543562 Sheth F et al. (2023)
c.252G>A p.Trp84Ter stop_gained Familial Maternal Simplex 37183190 D&#x27 et al. (2023)
c.98-?_1348+? - copy_number_loss Familial Paternal Simplex 37183190 D&#x27 et al. (2023)
c.3599C>T p.Ser1200Leu missense_variant Unknown - - 31209962 Aspromonte MC , et al. (2019)
c.622C>A p.Leu208Met missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.515T>C p.Ile172Thr missense_variant Familial Maternal - 33590427 Ohashi K et al. (2021)
c.158C>G p.Ser53Cys missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.3716-7_3716-6insTGT - intron_variant Unknown - Unknown 24083349 Worthey EA , et al. (2013)
c.511C>T p.Arg171Cys missense_variant Unknown - Unknown 24083349 Worthey EA , et al. (2013)
c.338A>G p.Tyr113Cys missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.416A>G p.Asn139Ser missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.824A>G p.His275Arg missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.860G>A p.Ser287Asn missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.963C>A p.Phe321Leu missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.3331C>T p.Gln1111Ter stop_gained Familial Paternal Simplex 37183190 D&#x27 et al. (2023)
c.97+?_209-?dup - copy_number_gain Familial Maternal Simplex 34641913 Scala M et al. (2021)
IVS10-1G>T - splice_site_variant Familial Paternal Simplex 19896112 Zweier C , et al. (2009)
c.853G>C p.Gly285Arg missense_variant Familial Paternal - 29271092 Kalsner L , et al. (2017)
c.1051G>A p.Ala351Thr missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.2123T>C p.Val708Ala missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.2205C>A p.Asn735Lys missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.2288A>G p.Asp763Gly missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.2476T>G p.Tyr826Asp missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.2657C>T p.Thr886Ile missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.2698C>T p.Arg900Trp missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.2820G>A p.Leu940%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1083G>A p.Val361= splice_site_variant Familial Maternal - 21827697 Gregor A , et al. (2011)
c.1083G>A p.Val361= splice_site_variant Familial Paternal - 21827697 Gregor A , et al. (2011)
c.3080G>C p.Arg1027Thr missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.3131C>T p.Pro1044Leu missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.3305T>C p.Val1102Ala missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.3470T>C p.Val1157Ala missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.3674C>T p.Ser1225Leu missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.3758T>C p.Ile1253Thr missense_variant Unknown - Simplex 25621974 Murdoch JD , et al. (2015)
c.1276C>A p.Leu426Ile missense_variant Unknown - Unknown 24066114 Koshimizu E , et al. (2013)
c.1448G>A p.Arg483Gln missense_variant Unknown - Unknown 24066114 Koshimizu E , et al. (2013)
c.2151C>A p.Tyr717Ter stop_gained Familial Both parents Simplex 37183190 D&#x27 et al. (2023)
c.400T>G p.Trp134Gly missense_variant Familial Maternal Simplex 37183190 D&#x27 et al. (2023)
c.550+5G>T - splice_site_variant Familial Both parents Multiplex 37183190 D&#x27 et al. (2023)
- - copy_number_loss Familial Both parents Extended multiplex 25045150 Watson CM , et al. (2014)
- - copy_number_loss Familial Both parents Multiplex 26843181 Rodenas-Cuadrado P , et al. (2016)
c.3262C>T p.Arg1088Ter stop_gained Familial Both parents Simplex 37183190 D&#x27 et al. (2023)
c.2449G>A p.Gly817Arg missense_variant Familial Paternal Simplex 37183190 D&#x27 et al. (2023)
c.1777+2T>C - splice_site_variant Familial Both parents Multiplex 37183190 D&#x27 et al. (2023)
- - complex_structural_alteration Familial Paternal Multiplex 12809671 Verkerk AJ , et al. (2003)
c.2151C>A p.Tyr717Ter stop_gained Familial Both parents - 34580403 Pode-Shakked B et al. (2021)
c.3046C>T p.Arg1016Ter stop_gained Familial Both parents Unknown 31139143 Long S , et al. (2019)
c.3046C>T p.Arg1016Ter stop_gained Familial Maternal Simplex 27439707 Smogavec M , et al. (2016)
c.1249G>T p.Asp417Tyr missense_variant Familial Maternal - 31209962 Aspromonte MC , et al. (2019)
c.3262C>T p.Arg1088Ter stop_gained Familial Both parents Multiplex 37183190 D&#x27 et al. (2023)
c.2752C> T p.Leu918Phe missense_variant Familial Paternal Simplex 34641913 Scala M et al. (2021)
c.403-1G>A - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.-215G>A - 2KB_upstream_variant Familial Paternal Simplex 25224256 Chiocchetti AG , et al. (2014)
c.824A>G p.His275Arg missense_variant Familial Maternal Simplex 21572417 O'Roak BJ , et al. (2011)
c.1105G>T p.Val369Leu missense_variant Familial Paternal Multiplex 28440294 Chen XS , et al. (2017)
c.1480G>T p.Glu494Ter stop_gained Familial Both parents Simplex 27439707 Smogavec M , et al. (2016)
- - copy_number_loss Familial Maternal and Paternal Extended multiplex 30586385 Toma C , et al. (2018)
c.2046C>A p.Cys682Ter stop_gained Familial Both parents Multiplex 27439707 Smogavec M , et al. (2016)
c.2191G>A p.Gly731Ser missense_variant Familial Paternal Simplex 18179895 Bakkaloglu B , et al. (2008)
c.2606T>C p.Ile869Thr missense_variant Familial Maternal Simplex 18179895 Bakkaloglu B , et al. (2008)
c.2606T>C p.Ile869Thr missense_variant Familial Paternal Simplex 18179895 Bakkaloglu B , et al. (2008)
c.682G>A p.Gly228Arg missense_variant Familial Both parents Multiplex 35911904 Badshah N et al. (2022)
c.3833C>T p.Thr1278Ile missense_variant Familial Maternal Simplex 18179895 Bakkaloglu B , et al. (2008)
c.2038G>A p.Glu680Lys missense_variant Familial Both parents Simplex 30675382 Leblond CS , et al. (2019)
c.2606T>C p.Ile869Thr missense_variant Familial Paternal Multiplex 18179895 Bakkaloglu B , et al. (2008)
c.2717G>A p.Arg906His missense_variant Familial Paternal Multiplex 18179895 Bakkaloglu B , et al. (2008)
c.1175_1176dup p.Asp393ArgfsTer51 frameshift_variant Familial Paternal - 21827697 Gregor A , et al. (2011)
c.3356G>A p.Arg1119His missense_variant Familial Paternal Multiplex 18179895 Bakkaloglu B , et al. (2008)
c.3385G>C p.Asp1129His missense_variant Familial Paternal Multiplex 18179895 Bakkaloglu B , et al. (2008)
c.3758T>C p.Ile1253Thr missense_variant Familial Maternal Multiplex 18179895 Bakkaloglu B , et al. (2008)
c.1628del p.Ser543IlefsTer13 frameshift_variant Familial Maternal Multiplex 37183190 D&#x27 et al. (2023)
c.3218A>T p.Asp1073Val missense_variant Familial Paternal Simplex 26845707 Alvarez-Mora MI , et al. (2016)
c.1680del p.Asn561IlefsTer45 frameshift_variant Familial Both parents Simplex 37183190 D&#x27 et al. (2023)
c.2964del p.Cys989AlafsTer45 frameshift_variant Familial Maternal Multiplex 27439707 Smogavec M , et al. (2016)
c.1361_1362del p.Asn454ArgfsTer24 frameshift_variant Familial Both parents Simplex 37183190 D&#x27 et al. (2023)
c.3407_3411del p.Tyr1136SerfsTer27 frameshift_variant Familial Both parents Simplex 37183190 D&#x27 et al. (2023)
c.1977_1989del13 p.Val660PhefsTer9 frameshift_variant Familial Maternal Multiplex 34778490 Mittal R et al. (2021)
c.1361_1362del p.Asn454ArgfsTer24 frameshift_variant Familial Both parents Multiplex 37183190 D&#x27 et al. (2023)
c.1780_1781dup p.Tyr595SerfsTer12 frameshift_variant Familial Both parents Multiplex 34582790 Mitani T et al. (2021)
c.3709del p.Asp1237IlefsTer17 frameshift_variant Familial Both parents Extended multiplex 16571880 Strauss KA , et al. (2006)
c.3679G>A p.Ala1227Thr missense_variant Familial Maternal & paternal Extended multiplex 18179895 Bakkaloglu B , et al. (2008)
Common Variants   (36)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
GCG[6]/GCG[7] - trinucleotide_repeat_microsatellite_feature - - - 25224256 Chiocchetti AG , et al. (2014)
c.402+30643C>T - intron_variant - - - 25337070 Poot M (2014)
c.403-32955T>G A/C intron_variant - - - 25337070 Poot M (2014)
c.3248-4A>G - intron_variant - - - 30017804 Gu H , et al. (2018)
c.1348+50804A>G - intron_variant - - - 20414140 Li X , et al. (2010)
c.208+18133A>T - intron_variant - - - 34257739 Fang F et al. (2021)
c.97+308723T>C - intron_variant - - - 22843504 Anney R , et al. (2012)
c.208+18133A>T - intron_variant - - - 33950402 Uddin MS et al. (2021)
c.208+18133A>T - intron_variant - - - 18179894 Arking DE , et al. (2008)
c.208+18133A>T - intron_variant - - - 26559825 Werling AM , et al. (2015)
c.208+18133A>T - intron_variant - - - 26909962 Nascimento PP , et al. (2016)
c.-876A>G - 2KB_upstream_variant - - - 25224256 Chiocchetti AG , et al. (2014)
c.1349-83693C>T G/A intron_variant - - - 21310003 Whitehouse AJ , et al. (2011)
c.*279C>A - intron_variant, 3_prime_UTR_variant - - - 30017804 Gu H , et al. (2018)
c.403-21804C>T Allele 1, A; allele 2, G intron_variant - - - 25337070 Poot M (2014)
c.2099-26267A>G;c.587-26267A>G - intron_variant - - - 35733350 Shiota Y et al. (2022)
c.2255+959T>A;c.743+959T>A A/T intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2099-18352A>G;c.587-18352A>G - intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2099-45850C>T;c.587-45850C>T - intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2255+31088A>G;c.743+31088A>G - intron_variant - - - 24147096 Sampath S , et al. (2013)
c.2099-26267A>G;c.587-26267A>G N/A intron_variant - - - 34898614 Shiota Y et al. (2021)
c.2099-26267A>G;c.587-26267A>G N/A intron_variant - - - 18179893 Alarcn M , et al. (2008)
c.2099-26267A>G;c.587-26267A>G N/A intron_variant - - - 21193173 Stein MB , et al. (2011)
c.2099-14838T>C;c.587-14838T>C G/A intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2099-21038A>C;c.587-21038A>C C/A intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2099-26267A>G;c.587-26267A>G C/T intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2099-73751C>T;c.587-73751C>T A/G intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2255+31322G>C;c.743+31322G>C G/C intron_variant - - - 24147096 Sampath S , et al. (2013)
c.2255+959T>A;c.743+959T>A A/G intron_variant - - - 21310003 Whitehouse AJ , et al. (2011)
c.2099-3491T>C;c.587-3491T>C A to G intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2099-18352A>G;c.587-18352A>G - intron_variant - - - 21310003 Whitehouse AJ , et al. (2011)
c.2099-24246C>T;c.587-24246C>T T to C intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2099-25545A>C;c.587-25545A>C G to T intron_variant - - - 18987363 Vernes SC , et al. (2008)
c.2099-14838T>C;c.587-14838T>C G/A intron_variant - - - 21310003 Whitehouse AJ , et al. (2011)
c.2099-26267A>G;c.587-26267A>G C/T intron_variant - - - 21310003 Whitehouse AJ , et al. (2011)
c.2099-25545A>C;c.587-25545A>C G to T intron_variant - - - 21310003 Whitehouse AJ , et al. (2011)
SFARI Gene score
2S

Strong Candidate, Syndromic

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216). Functional analysis of several CNTNAP2 missense variants originally identified in ASD cases in Bakkaloglu et al., 2008 demonstrated impaired axonal outgrowth in cortical neurons (Canali et al., 2018).

Score Delta: Score remained at 2S

2

Strong Candidate

See all Category 2 Genes

We 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.

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2021
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216). Functional analysis of several CNTNAP2 missense variants originally identified in ASD cases in Bakkaloglu et al., 2008 demonstrated impaired axonal outgrowth in cortical neurons (Canali et al., 2018).

1/1/2021
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216). Functional analysis of several CNTNAP2 missense variants originally identified in ASD cases in Bakkaloglu et al., 2008 demonstrated impaired axonal outgrowth in cortical neurons (Canali et al., 2018).

7/1/2020
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216). Functional analysis of several CNTNAP2 missense variants originally identified in ASD cases in Bakkaloglu et al., 2008 demonstrated impaired axonal outgrowth in cortical neurons (Canali et al., 2018).

10/1/2019
2S
icon
2S

Score remained at 2S

New Scoring Scheme
Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216). Functional analysis of several CNTNAP2 missense variants originally identified in ASD cases in Bakkaloglu et al., 2008 demonstrated impaired axonal outgrowth in cortical neurons (Canali et al., 2018).

7/1/2019
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216). Functional analysis of several CNTNAP2 missense variants originally identified in ASD cases in Bakkaloglu et al., 2008 demonstrated impaired axonal outgrowth in cortical neurons (Canali et al., 2018).

1/1/2019
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216). Functional analysis of several CNTNAP2 missense variants originally identified in ASD cases in Bakkaloglu et al., 2008 demonstrated impaired axonal outgrowth in cortical neurons (Canali et al., 2018).

7/1/2018
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216). Functional analysis of several CNTNAP2 missense variants originally identified in ASD cases in Bakkaloglu et al., 2008 demonstrated impaired axonal outgrowth in cortical neurons (Canali et al., 2018).

10/1/2017
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

7/1/2017
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

4/1/2017
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

Reports Added
[Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.2008] [A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism.2008] [Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders.2008] [A functional genetic link between distinct developmental language disorders.2008] [Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder.2009] [Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population.2010] [Identification of a microdeletion at the 7q33-q35 disrupting the CNTNAP2 gene in a Brazilian stuttering case.2010] [CNTNAP2 variants affect early language development in the general population.2011] [Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Individual common variants exert weak effects on the risk for autism spectrum disorderspi.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.2013] [Refinement and discovery of new hotspots of copy-number variation associated with 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] [Defining the contribution of CNTNAP2 to autism susceptibility.2013] [Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.2014] [Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach.2014] [A candidate gene association study further corroborates involvement of contactin genes in autism.2014] [No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contacti...2015] [Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.2012] [Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.2013] [Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...2011] [Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay.2012] [Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.2006] [Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.2010] [Rare copy number variants are an important cause of epileptic encephalopathies.2011] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [Diagnostic whole genome sequencing and split-read mapping for nucleotide resolution breakpoint identification in CNTNAP2 deficiency syndrome.2014] [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 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder.2003] [CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.2007] [A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-relat...2011] [Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K channels.2000] [Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons.2008] [Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS.2009] [Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B.2010] [Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.2010] [Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2.2010] [Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits.2011] [Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development.2012] [CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.2013] [CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.2015] [Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.2015] [Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2.2016] [Characterisation of CASPR2 deficiency disorder - a syndrome involving autism, epilepsy and language impairment.2016] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Single nucleotide polymorphisms in the CNTNAP2 gene in Brazilian patients with autistic spectrum disorder.2016] [Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells.2016] [Eight further individuals with intellectual disability and epilepsy carrying bi-allelic CNTNAP2 aberrations allow delineation of the mutational and...2016] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [Associations between the CNTNAP2 gene, dorsolateral prefrontal cortex, and cognitive performance on the Stroop task.2016] [Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment.2017]
1/1/2017
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

10/1/2016
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

7/1/2016
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

4/1/2016
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

Reports Added
[Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.2008] [A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism.2008] [Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders.2008] [A functional genetic link between distinct developmental language disorders.2008] [Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder.2009] [Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population.2010] [Identification of a microdeletion at the 7q33-q35 disrupting the CNTNAP2 gene in a Brazilian stuttering case.2010] [CNTNAP2 variants affect early language development in the general population.2011] [Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Individual common variants exert weak effects on the risk for autism spectrum disorderspi.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.2013] [Refinement and discovery of new hotspots of copy-number variation associated with 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] [Defining the contribution of CNTNAP2 to autism susceptibility.2013] [Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.2014] [Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach.2014] [A candidate gene association study further corroborates involvement of contactin genes in autism.2014] [No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contacti...2015] [Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.2012] [Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.2013] [Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...2011] [Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay.2012] [Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.2006] [Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.2010] [Rare copy number variants are an important cause of epileptic encephalopathies.2011] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [Diagnostic whole genome sequencing and split-read mapping for nucleotide resolution breakpoint identification in CNTNAP2 deficiency syndrome.2014] [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 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder.2003] [CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.2007] [A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-relat...2011] [Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K channels.2000] [Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons.2008] [Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS.2009] [Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B.2010] [Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.2010] [Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2.2010] [Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits.2011] [Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development.2012] [CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.2013] [CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.2015] [Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.2015] [Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2.2016] [Characterisation of CASPR2 deficiency disorder - a syndrome involving autism, epilepsy and language impairment.2016] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Single nucleotide polymorphisms in the CNTNAP2 gene in Brazilian patients with autistic spectrum disorder.2016] [Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells.2016]
1/1/2016
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

Reports Added
[Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.2008] [A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism.2008] [Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders.2008] [A functional genetic link between distinct developmental language disorders.2008] [Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder.2009] [Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population.2010] [Identification of a microdeletion at the 7q33-q35 disrupting the CNTNAP2 gene in a Brazilian stuttering case.2010] [CNTNAP2 variants affect early language development in the general population.2011] [Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Individual common variants exert weak effects on the risk for autism spectrum disorderspi.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.2013] [Refinement and discovery of new hotspots of copy-number variation associated with 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] [Defining the contribution of CNTNAP2 to autism susceptibility.2013] [Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.2014] [Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach.2014] [A candidate gene association study further corroborates involvement of contactin genes in autism.2014] [No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contacti...2015] [Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.2012] [Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.2013] [Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...2011] [Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay.2012] [Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.2006] [Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.2010] [Rare copy number variants are an important cause of epileptic encephalopathies.2011] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [Diagnostic whole genome sequencing and split-read mapping for nucleotide resolution breakpoint identification in CNTNAP2 deficiency syndrome.2014] [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 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder.2003] [CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.2007] [A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-relat...2011] [Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K channels.2000] [Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons.2008] [Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS.2009] [Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B.2010] [Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.2010] [Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2.2010] [Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits.2011] [Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development.2012] [CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.2013] [CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.2015] [Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.2015] [Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2.2016] [Characterisation of CASPR2 deficiency disorder - a syndrome involving autism, epilepsy and language impairment.2016] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Single nucleotide polymorphisms in the CNTNAP2 gene in Brazilian patients with autistic spectrum disorder.2016]
1/1/2015
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

10/1/2014
2S
icon
2S

Score remained at 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

7/1/2014
No data
icon
2S

Increased from No data to 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

Reports Added
[Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K channels.2000] [CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder.2003] [Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.2006] [CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.2007] [Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.2008] [A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism.2008] [Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders.2008] [A functional genetic link between distinct developmental language disorders.2008] [Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons.2008] [Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS.2009] [Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder.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] [Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B.2010] [Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.2010] [Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population.2010] [Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.2010] [Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2.2010] [Identification of a microdeletion at the 7q33-q35 disrupting the CNTNAP2 gene in a Brazilian stuttering case.2010] [A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-relat...2011] [CNTNAP2 variants affect early language development in the general population.2011] [Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits.2011] [Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...2011] [Rare copy number variants are an important cause of epileptic encephalopathies.2011] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.2012] [Individual common variants exert weak effects on the risk for autism spectrum disorderspi.2012] [Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development.2012] [Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.2013] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.2013] [Defining the contribution of CNTNAP2 to autism susceptibility.2013] [Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.2014] [Diagnostic whole genome sequencing and split-read mapping for nucleotide resolution breakpoint identification in CNTNAP2 deficiency syndrome.2014]
4/1/2014
No data
icon
2S

Increased from No data to 2S

Description

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216).

Krishnan Probability Score

Score 0.61403089293347

Ranking 134/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 3.8288260734217E-5

Ranking 13588/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.95084116029586

Ranking 18649/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Larsen Cumulative Evidence Score

Score 59

Ranking 27/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.28409542588975

Ranking 2965/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ADAM11 Disintegrin and metalloproteinase domain-containing protein 11 Mouse Protein Binding 11488 Q9R1V4
ADAM22 Disintegrin and metalloproteinase domain-containing protein 22 Mouse Protein Binding 11496 Q9R1V6
ADAM23 Disintegrin and metalloproteinase domain-containing protein 23 Mouse Protein Binding 23792 Q9R1V7
CASK calcium/calmodulin-dependent serine protein kinase (MAGUK family) Mouse Protein Binding 12361 O70589
CKMT1 Creatine kinase U-type, mitochondrial Mouse Protein Binding 12716 P30275
CNTN2 contactin 2 (axonal) Human Protein Binding 6900 Q02246
KCNA1 Potassium voltage-gated channel subfamily A member 1 Mouse Protein Binding 16485 P16388
KCNA2 potassium voltage-gated channel, shaker-related subfamily, member 2 Mouse Protein Binding 16490 P63141
KCNA3 Potassium voltage-gated channel subfamily D member 3 Mouse Protein Binding 56543 Q9Z0V1
KCNA4 potassium voltage-gated channel, shaker-related subfamily, member 4 Mouse Protein Binding 16492 Q61423
KCNA6 Potassium voltage-gated channel subfamily A member 6 Mouse Protein Binding 16494 Q61923
KCNAB2 Voltage-gated potassium channel subunit beta-2 Mouse Protein Binding 16498 P62482
LGI2 leucine-rich repeat LGI family, member 2 Mouse Protein Binding 246316 Q8K4Z0
LGI3 Leucine-rich repeat LGI family member 3 Mouse Protein Binding 213469 Q8K406
LGI4 Leucine-rich repeat LGI family member 4 Mouse Protein Binding 243914 Q8K1S1
Mpdz multiple PDZ domain protein Rat Protein Binding 29365 O55164
PDIA3 protein disulfide isomerase family A, member 3 Human Protein Binding 2923 P30101
STOX1 storkhead box 1 Human DNA Binding 219736 Q6ZVD7
TPI1 Triosephosphate isomerase Mouse Protein Binding 21991 P17751
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