Human Gene Module / Chromosome 20 / ADNP

ADNPActivity-dependent neuroprotector homeobox

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
43 / 88
Rare Variants / Common Variants
190 / 0
EAGLE Score
41.5
Strong Learn More
Aliases
ADNP, ADNP1
Associated Syndromes
Helsmoortel-Van der Aa syndrome, ASD, ID, Helsmoortel-van der Aa syndrome, Helsmoortel-Van der Aa syndrome, DD, ID, Helsmoortel-van der Aa syndrome, DD, Helsmoortel-van der Aa syndrome, ASD, DD, Helsmoortel-van der Aa syndrome, ASD, DD, ID, Helsmoortel-van der Aa syndrome, ASD, DD, epilepsy
Chromosome Band
20q13.13
Associated Disorders
DD/NDD, ADHD, ID, EPS, ASD
Genetic Category
Rare Single Gene Mutation, Syndromic, Functional
Relevance to Autism

Recurrent mutations in the ADNP gene have been identified in multiple individuals with ASD as described below. Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases in two reports by O'Roak and colleagues in 2012 (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; the probability of detecting eight or more de novo truncating events in ADNP was given as P=2.65 x 10-18 in this report (PMID 24531329). Furthermore, the frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led Helsmoortel and colleagues to conclude that ADNP mutations resulted in an autism syndrome. Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified ADNP as a gene reaching exome-wide significance (P < 2.5E-06).

Molecular Function

Potential transcription factor that may mediate some of the neuroprotective peptide VIP-associated effects involving normal growth and cancer proliferation. In brain, expression is stronger in the cerebellum and cortex regions.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ADNP (88 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Support Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders O'Roak BJ , et al. (2012) Yes -
3 Recent Recommendation A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP Helsmoortel C , et al. (2014) No ASD, DD, ID, epilepsy
4 Support Expansion of the clinical phenotype associated with mutations in activity-dependent neuroprotective protein Pescosolido MF et al. (2014) No DD, ADHD
5 Support Challenges and opportunities in the investigation of unexplained intellectual disability using family-based whole-exome sequencing Helsmoortel C et al. (2015) No ASD, DD, ID
6 Recent Recommendation The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism Vandeweyer G , et al. (2014) Yes ID
7 Recent Recommendation The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins Oz S , et al. (2014) No -
8 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
9 Support Recurrent de novo mutations implicate novel genes underlying simplex autism risk O'Roak BJ , et al. (2014) Yes -
10 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) Yes -
11 Recent Recommendation Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies Malishkevich A , et al. (2015) No -
12 Support The Compassionate Side of Neuroscience: Tony Sermone's Undiagnosed Genetic Journey--ADNP Mutation Gozes I , et al. (2015) Yes -
13 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
14 Support Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
15 Support Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms D'Gama AM , et al. (2015) Yes -
16 Support Comprehensive molecular testing in patients with high functioning autism spectrum disorder Alvarez-Mora MI , et al. (2016) Yes -
17 Support Additional data on the clinical phenotype of Helsmoortel-Van der Aa syndrome associated with a novel truncating mutation in ADNP gene Krajewska-Walasek M , et al. (2016) No ASD, DD, ID
18 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
19 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
20 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
21 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families Trujillano D , et al. (2016) No -
22 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases Stessman HA , et al. (2017) Yes -
23 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
24 Support Further evidence that a blepharophimosis syndrome phenotype is associated with a specific class of mutation in the ADNP gene Takenouchi T , et al. (2017) No -
25 Support Novel features of Helsmoortel-Van der Aa/ADNP syndrome in a boy with a known pathogenic mutation in the ADNP gene detected by exome sequencing Li C et al. (2017) No DD
26 Support The Eight and a Half Year Journey of Undiagnosed AD: Gene Sequencing and Funding of Advanced Genetic Testing Has Led to Hope and New Beginnings Gozes I et al. (2017) No ASD, DD, ID
27 Support Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients Chrot E , et al. (2017) No -
28 Support Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice Tumien B , et al. (2017) No Stereotypic behavior, aggressive behavior
29 Support Mutation in the ADNP gene associated with Noonan syndrome features Alkhunaizi E et al. (2018) No ASD, DD, ID
30 Support Helsmoortel-Van der Aa Syndrome as emerging clinical diagnosis in intellectually disabled children with autistic traits and ocular involvement Pascolini G , et al. (2018) No Autistic behavior
31 Recent Recommendation Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP Van Dijck A , et al. (2018) No ASD or autistic features
32 Support Longitudinal ophthalmic findings in a child with Helsmoortel-Van der Aa Syndrome Gale MJ , et al. (2018) No DD, ID
33 Support A heterozygous microdeletion of 20q13.13 encompassing ADNP gene in a child with Helsmoortel-van der Aa syndrome Huynh MT , et al. (2018) No ID, autistic features
34 Support The autism spectrum phenotype in ADNP syndrome Arnett AB , et al. (2018) No ASD
35 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes Guo H , et al. (2018) Yes -
36 Support Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder Du X , et al. (2018) Yes DD/ID
37 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
38 Support Both rare and common genetic variants contribute to autism in the Faroe Islands Leblond CS , et al. (2019) Yes -
39 Support Cellular and animal models of skin alterations in the autism-related ADNP syndrome Mollinedo P et al. (2019) No ASD, ID
40 Support Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome Bend EG , et al. (2019) No -
41 Support Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort Callaghan DB , et al. (2019) Yes -
42 Support Developmental Phenotype of the Rare Case of DJ Caused by a Unique ADNP Gene De Novo Mutation Levine J , et al. (2019) Yes ADHD, behavioral problems
43 Support Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population Monies D , et al. (2019) Yes -
44 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 -
45 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
46 Recent Recommendation Discovery of autism/intellectual disability somatic mutations in Alzheimer's brains: mutated ADNP cytoskeletal impairments and repair as a case study Ivashko-Pachima Y , et al. (2019) No -
47 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
48 Support Early behavioral and developmental interventions in ADNP-syndrome: A case report of SWI/SNF-related neurodevelopmental syndrome Shillington A et al. (2020) No ASD
49 Support ADNP Controls Gene Expression Through Local Chromatin Architecture by Association With BRG1 and CHD4 Sun X et al. (2020) No -
50 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes DD, ID
51 Support - Ohashi K et al. (2021) Yes -
52 Support - Abe-Hatano C et al. (2021) Yes -
53 Support - Valentino F et al. (2021) No Epilepsy/seizures
54 Support - Mahjani B et al. (2021) Yes -
55 Support - Karmon G et al. (2021) No -
56 Support - Álvarez-Mora MI et al. (2022) No -
57 Support - Brea-Fernández AJ et al. (2022) No Epilepsy/seizures
58 Support - Ivashko-Pachima Y et al. (2022) Yes -
59 Support - Chuan Z et al. (2022) No -
60 Support - Conrow-Graham M et al. (2022) No -
61 Support - Krgovic D et al. (2022) Yes ADHD, DD, ID
62 Support - Levchenko O et al. (2022) No -
63 Support - Zhou X et al. (2022) Yes ADHD, SCZ, epilepsy/seizures
64 Support - Ganaiem M et al. (2022) No Alzheimer's disease
65 Support - Shimelis H et al. (2023) Yes -
66 Support - Szab TM et al. (2022) No Autistic features, stereotypy
67 Support - Bennison SA et al. (2023) No -
68 Support - Gozes I et al. (2023) No -
69 Support - Georget M et al. (2023) No Autistic features
70 Recent Recommendation - Kundishora AJ et al. (2023) No ASD, DD, epilepsy/seizures
71 Support - Spataro N et al. (2023) No ASD
72 Support - Zhang Y et al. (2023) Yes ID
73 Support - Chen LJ et al. (2023) No -
74 Recent Recommendation - Timberlake AT et al. (2023) No ASD
75 Support - Cho H et al. (2023) No -
76 Support - Bartolomaeus T et al. (2023) No -
77 Support - Cirnigliaro M et al. (2023) Yes -
78 Support - Karthika Ajit Valaparambil et al. () Yes -
79 Support - Giulia Pascolini et al. (2024) Yes Stereotypy
80 Support - Chuanhui Ge et al. (2024) No ASD, DD, ID
81 Support - Claudio Peter D'Incal et al. (2024) Yes -
82 Support - Tamam Khalaf et al. (2024) No ASD
83 Support - Yasser Al-Sarraj et al. (2024) Yes -
84 Support - Lei Wan et al. (2024) Yes -
85 Support - Emily Neuhaus et al. (2024) Yes Oppositional features
86 Support - Claudio D'Incal et al. (2024) Yes -
87 Support - Ruohao Wu et al. (2024) Yes -
88 Support - Camilla Sarli et al. () No -
Rare Variants   (190)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - Simplex 29899371 Huynh MT , et al. (2018)
c.893T>G p.Leu298Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.484C>T p.Gln162Ter stop_gained Unknown - - 35982159 Zhou X et al. (2022)
c.1102C>T p.Gln368Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
c.1930C>T p.Arg644Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.2157C>A p.Tyr719Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
c.2157C>A p.Tyr719Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.2157C>G p.Tyr719Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
c.2157C>G p.Tyr719Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.2188C>T p.Arg730Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.2382G>A p.Trp794Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.1102C>T p.Gln368Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.2157C>A p.Tyr719Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.2157C>G p.Tyr719Ter stop_gained Unknown - - 35982159 Zhou X et al. (2022)
c.2188C>T p.Arg730Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.632T>A p.Leu211Ter stop_gained De novo - - 27824329 Wang T , et al. (2016)
c.568C>T p.Gln190Ter stop_gained De novo - - 37063667 Chen LJ et al. (2023)
c.2157C>G p.Tyr719Ter stop_gained De novo - - 28579975 Gozes I et al. (2017)
c.2213C>A p.Ser738Ter stop_gained De novo - - 36553633 Szab TM et al. (2022)
c.2156dup p.Tyr719Ter stop_gained De novo - - 37035742 Zhang Y et al. (2023)
c.517C>T p.Arg173Ter stop_gained De novo - - 28708303 Chrot E , et al. (2017)
c.2157C>G p.Tyr719Ter stop_gained De novo - - 29780943 Gale MJ , et al. (2018)
c.110A>T p.Asp37Val missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.253T>C p.Phe85Leu missense_variant De novo - - 33004838 Wang T et al. (2020)
c.2188C>T p.Arg730Ter stop_gained De novo - - 29286531 Tumien B , et al. (2017)
c.2188C>T p.Arg730Ter stop_gained De novo - - 35813072 Krgovic D et al. (2022)
c.715C>G p.His239Asp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2712dup p.Asn905Ter stop_gained Familial - - 36980980 Spataro N et al. (2023)
c.1102C>T p.Gln368Ter stop_gained Unknown - - 30107084 Arnett AB , et al. (2018)
c.2157C>A p.Tyr719Ter stop_gained De novo - - 30107084 Arnett AB , et al. (2018)
c.673C>T p.Arg225Ter stop_gained De novo - - 38254177 Chuanhui Ge et al. (2024)
c.1535T>G p.Leu512Arg missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1540T>G p.Cys514Gly missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1568A>C p.Asp523Ala missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1931G>A p.Arg644Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1594C>T p.Arg532Trp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2157C>A p.Tyr719Ter stop_gained De novo - - 38254177 Chuanhui Ge et al. (2024)
c.2157C>A p.Tyr719Ter stop_gained Unknown - - 38254177 Chuanhui Ge et al. (2024)
c.673C>T p.Arg225Ter stop_gained De novo - - 28191889 Stessman HA , et al. (2017)
c.1084C>G p.Gln362Glu missense_variant De novo - - 36669790 Gozes I et al. (2023)
c.2188C>T p.Arg730Ter stop_gained De novo - - 27479843 Lelieveld SH et al. (2016)
c.2213C>G p.Ser738Ter stop_gained De novo - - 28191889 Stessman HA , et al. (2017)
c.1360G>T p.Glu454Ter stop_gained Unknown - - 38438125 Tamam Khalaf et al. (2024)
c.2156dup p.Tyr719Ter frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1917T>C p.Leu639%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.3281G>A p.Gly1094Glu missense_variant De novo - - 35571021 Chuan Z et al. (2022)
c.2157C>G p.Tyr719Ter stop_gained De novo - - 28407407 Takenouchi T , et al. (2017)
c.1211C>A p.Ser404Ter stop_gained De novo - - 24531329 Helsmoortel C , et al. (2014)
c.1930C>T p.Arg644Ter stop_gained Unknown - - 24531329 Helsmoortel C , et al. (2014)
c.2157C>G p.Tyr719Ter stop_gained De novo - - 24531329 Helsmoortel C , et al. (2014)
c.2156dup p.Tyr719Ter frameshift_variant De novo - - 28708303 Chrot E , et al. (2017)
- - copy_number_loss Unknown Not maternal Simplex 30675382 Leblond CS , et al. (2019)
c.673C>T p.Arg225Ter stop_gained De novo - - 38204290 Giulia Pascolini et al. (2024)
c.-89-3923_201+2793inv - inversion De novo - Simplex 36828924 Georget M et al. (2023)
c.517C>T p.Arg173Ter stop_gained De novo - Simplex 31406558 Munnich A , et al. (2019)
c.2157C>G p.Tyr719Ter stop_gained De novo - - 38204290 Giulia Pascolini et al. (2024)
c.2157del p.Tyr719Ter stop_gained De novo - - 38204290 Giulia Pascolini et al. (2024)
c.2188C>T p.Arg730Ter stop_gained De novo - - 38204290 Giulia Pascolini et al. (2024)
c.2T>C p.Met1? initiator_codon_variant De novo - Simplex 30555518 Du X , et al. (2018)
c.334_335insA p.Cys112Ter frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.3170T>A p.Leu1057Ter stop_gained De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.790C>T p.Arg264Ter stop_gained Unknown - Unknown 35887114 Levchenko O et al. (2022)
c.190dup p.Thr64AsnfsTer35 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.287del p.Val96AlafsTer65 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2156dup p.Tyr719Ter frameshift_variant Unknown - - 30679581 Mollinedo P et al. (2019)
c.2157C>G p.Tyr719Ter stop_gained De novo - Simplex 38254177 Chuanhui Ge et al. (2024)
c.2188C>T p.Arg730Ter stop_gained De novo - Simplex 38254177 Chuanhui Ge et al. (2024)
c.118C>T p.Gln40Ter stop_gained De novo - Simplex 25169753 Vandeweyer G , et al. (2014)
c.339del p.Phe114SerfsTer47 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.819del p.Lys274AsnfsTer31 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.1713dup p.Arg572GlufsTer6 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2231del p.Glu744GlyfsTer9 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2287del p.Ser763ProfsTer9 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.103dup p.Ile35AsnfsTer5 frameshift_variant Unknown - - 31029150 Bend EG , et al. (2019)
c.10C>G p.Leu4Val frameshift_variant Unknown - Unknown 31130284 Monies D , et al. (2019)
c.2157C>G p.Tyr719Ter stop_gained De novo - Simplex 29475819 Pascolini G , et al. (2018)
c.2188C>T p.Arg730Ter stop_gained De novo - Simplex 29475819 Pascolini G , et al. (2018)
c.1287dup p.Ala430CysfsTer10 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2318dup p.Tyr774ValfsTer14 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.3047dup p.Ala1017GlyfsTer6 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1049dup p.Leu351SerfsTer48 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.2457del p.Lys819AsnfsTer10 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.3047dup p.Ala1017GlyfsTer6 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.3170T>A p.Leu1057Ter stop_gained De novo - Simplex 28191889 Stessman HA , et al. (2017)
c.2157C>A p.Tyr719Ter stop_gained De novo - - 35322241 Brea-Fernández AJ et al. (2022)
c.2188C>T p.Arg730Ter stop_gained De novo - - 35322241 Brea-Fernández AJ et al. (2022)
c.2288C>T p.Ser763Phe missense_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.1035_1038del p.Ser346Ter frameshift_variant De novo - - 28263302 C Yuen RK et al. (2017)
c.498_499del p.Tyr166Ter stop_gained De novo - Simplex 38254177 Chuanhui Ge et al. (2024)
c.2808del p.Tyr936Ter frameshift_variant De novo - - 24531329 Helsmoortel C , et al. (2014)
c.2157C>G p.Tyr719Ter stop_gained De novo - Simplex 25057125 Pescosolido MF et al. (2014)
c.2261T>G p.Leu754Ter stop_gained De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1327A>G p.Thr443Ala missense_variant Unknown - - 26845707 Alvarez-Mora MI , et al. (2016)
c.361_362del p.Leu121GlyfsTer5 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.2126C>T p.Ser709Phe missense_variant Familial Maternal - 33590427 Ohashi K et al. (2021)
c.2772G>C p.Glu924Asp missense_variant Familial Paternal - 33590427 Ohashi K et al. (2021)
c.190dup p.Thr64AsnfsTer35 frameshift_variant De novo - - 30107084 Arnett AB , et al. (2018)
c.287del p.Val96AlafsTer65 frameshift_variant Unknown - - 30107084 Arnett AB , et al. (2018)
c.3170T>A p.Leu1057Ter stop_gained De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2491_2494del p.Leu831IlefsTer82 frameshift_variant De novo - - 28475273 Li C et al. (2017)
c.539_542del p.Val180GlyfsTer17 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.853_857del p.Pro285AspfsTer27 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.3127G>T p.Asp1043Tyr missense_variant Familial Maternal - 33590427 Ohashi K et al. (2021)
c.339del p.Phe114SerfsTer47 frameshift_variant Unknown - - 30107084 Arnett AB , et al. (2018)
c.819del p.Lys274AsnfsTer31 frameshift_variant De novo - - 30107084 Arnett AB , et al. (2018)
c.2287del p.Ser763ProfsTer9 frameshift_variant Unknown - - 30107084 Arnett AB , et al. (2018)
c.3281G>T p.Gly1094Val missense_variant Unknown - Unknown 26637798 D'Gama AM , et al. (2015)
c.2059T>C p.Cys687Arg missense_variant De novo - Simplex 38254177 Chuanhui Ge et al. (2024)
c.2188C>G p.Arg730Gly missense_variant De novo - Simplex 38254177 Chuanhui Ge et al. (2024)
c.2157C>A p.Tyr719Ter stop_gained De novo - Simplex 38572415 Yasser Al-Sarraj et al. (2024)
c.1402_1403del p.Glu468ThrfsTer2 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2421_2422del p.Arg808GlufsTer6 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.2825_2828del p.Thr942ArgfsTer6 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.539_542del p.Val180GlyfsTer17 frameshift_variant De novo - - 36553633 Szab TM et al. (2022)
c.2289del p.Tyr764MetfsTer8 frameshift_variant Unknown - - 38254177 Chuanhui Ge et al. (2024)
c.1553G>A p.Arg518His missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1668G>C p.Gln556His missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2881G>T p.Asp961Tyr missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1046_1047del p.Leu349ArgfsTer49 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.1046_1047del p.Leu349ArgfsTer49 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2194_2197del p.Leu732MetfsTer20 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2491_2494del p.Leu831IlefsTer82 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.2496_2499del p.Asn832LysfsTer81 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.1004_1005del p.Lys335IlefsTer63 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.1239_1240del p.Gln414ValfsTer25 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.3069_3072del p.Arg1023SerfsTer3 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.3136_3137del p.Gln1046ValfsTer6 frameshift_variant Unknown - - 35982159 Zhou X et al. (2022)
c.2314dup p.Thr772AsnfsTer16 frameshift_variant Unknown - - 34356170 Valentino F et al. (2021)
c.746A>G p.Tyr249Cys missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1792C>T p.Gln598Ter stop_gained De novo - Simplex 35183220 Álvarez-Mora MI et al. (2022)
c.1035_1038del p.Ser346Ter frameshift_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.311A>G p.Lys104Arg missense_variant Unknown - - 37943464 Karthika Ajit Valaparambil et al. ()
c.-5-1_-4del - splice_site_variant De novo - - 38424297 Claudio Peter D'Incal et al. (2024)
c.539_542del p.Val180GlyfsTer17 frameshift_variant Unknown - - 36475376 Shimelis H et al. (2023)
c.294_295del p.Ser98ArgfsTer4 frameshift_variant Unknown - - 38438125 Tamam Khalaf et al. (2024)
c.2157del p.Tyr719Ter frameshift_variant De novo - Simplex 27848944 Trujillano D , et al. (2016)
c.2188C>T p.Arg730Ter stop_gained De novo - Simplex 27031564 Krajewska-Walasek M , et al. (2016)
c.2317_2318del p.Lys773ValfsTer14 frameshift_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.2496_2499del p.Asn832LysfsTer81 frameshift_variant De novo - - 35813072 Krgovic D et al. (2022)
c.3071_3072del p.Glu1024AlafsTer7 frameshift_variant Unknown - - 35813072 Krgovic D et al. (2022)
c.2194_2197del p.Leu732MetfsTer20 frameshift_variant De novo - - 36980980 Spataro N et al. (2023)
c.2491_2494del p.Leu831IlefsTer82 frameshift_variant De novo - - 36980980 Spataro N et al. (2023)
c.537dup p.Val180SerfsTer2 frameshift_variant De novo - Simplex 31127536 Levine J , et al. (2019)
c.64dup p.Ile22AsnfsTer3 frameshift_variant De novo - Simplex 38254177 Chuanhui Ge et al. (2024)
c.3047dup p.Ala1017GlyfsTer6 frameshift_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.1046_1047del p.Leu349ArgfsTer49 frameshift_variant De novo - - 30107084 Arnett AB , et al. (2018)
c.2250_2274del p.Val751MetfsTer13 frameshift_variant De novo - - 30107084 Arnett AB , et al. (2018)
c.2496_2499del p.Asn832LysfsTer81 frameshift_variant De novo - - 30107084 Arnett AB , et al. (2018)
c.2355_2356del p.Glu785AspfsTer2 frameshift_variant De novo - - 38254177 Chuanhui Ge et al. (2024)
c.651_655del p.Glu218Ter frameshift_variant De novo - Simplex 29424797 Alkhunaizi E et al. (2018)
c.319del p.Asn108IlefsTer53 frameshift_variant De novo - - 38204290 Giulia Pascolini et al. (2024)
c.2189del p.Arg730GlnfsTer3 frameshift_variant De novo - - 38204290 Giulia Pascolini et al. (2024)
c.2222dup p.Phe742LeufsTer2 frameshift_variant De novo - - 38204290 Giulia Pascolini et al. (2024)
c.3047dup p.Ala1017GlyfsTer6 frameshift_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.2251_2275del p.Val751MetfsTer13 frameshift_variant De novo - - 31452935 Feliciano P et al. (2019)
c.370_381del p.His124_Ile127del inframe_deletion De novo - Simplex 38764027 Ruohao Wu et al. (2024)
c.1026dup p.Val343CysfsTer56 frameshift_variant De novo - Simplex 25418537 O'Roak BJ , et al. (2014)
c.2499del p.Val834SerfsTer80 frameshift_variant De novo - Simplex 31406558 Munnich A , et al. (2019)
c.2155del p.Tyr719ThrfsTer9 frameshift_variant De novo - Simplex 35887114 Levchenko O et al. (2022)
c.2491_2494del p.Leu831IlefsTer82 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.3066_3069del p.Asp1022GlufsTer4 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.2496_2499del p.Asn832LysfsTer81 frameshift_variant De novo - - 32275126 Shillington A et al. (2020)
c.2153_2165del p.Thr718ArgfsTer6 frameshift_variant De novo - - 24531329 Helsmoortel C , et al. (2014)
c.2491_2494del p.Leu831IlefsTer82 frameshift_variant De novo - - 24531329 Helsmoortel C , et al. (2014)
c.2496_2499del p.Asn832LysfsTer81 frameshift_variant De novo - - 24531329 Helsmoortel C , et al. (2014)
c.1676dup p.His559GlnfsTer3 frameshift_variant De novo - - 38637827 Claudio D'Incal et al. (2024)
c.2250_2274del p.Val751MetfsTer13 frameshift_variant De novo - Multiplex 30504930 Guo H , et al. (2018)
c.1046_1047del p.Leu349ArgfsTer49 frameshift_variant De novo - Simplex 26168855 Gozes I , et al. (2015)
c.2287dup p.Ser763PhefsTer3 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.642_649del p.Asn214LysfsTer4 frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1026dup p.Val343CysfsTer56 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2491_2494del p.Leu831IlefsTer82 frameshift_variant De novo - - 38204290 Giulia Pascolini et al. (2024)
c.2496_2499del p.Asn832LysfsTer81 frameshift_variant De novo - - 38204290 Giulia Pascolini et al. (2024)
c.1222_1223del p.Lys408ValfsTer31 frameshift_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.642_651del p.Asn214LysfsTer31 frameshift_variant De novo - Simplex 33624935 Abe-Hatano C et al. (2021)
c.2156_2157insT p.Glu720ArgfsTer15 frameshift_variant De novo - Simplex 23160955 O'Roak BJ , et al. (2012)
c.2491_2494del p.Leu831IlefsTer82 frameshift_variant De novo - Simplex 38254177 Chuanhui Ge et al. (2024)
c.2155del p.Tyr719ThrfsTer9 frameshift_variant Unknown Not maternal Simplex 30564305 Guo H , et al. (2018)
c.2866_2869del p.Glu956LeufsTer35 frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.2318_2319del p.Lys773IlefsTer14 frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1222_1223del p.Lys408ValfsTer31 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2424_2427del p.Lys809SerfsTer19 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2496_2499del p.Asn832LysfsTer81 frameshift_variant De novo - Simplex 37460657 Bartolomaeus T et al. (2023)
c.2798_2799del p.Gly933ValfsTer10 frameshift_variant Unknown - Multiplex 31038196 Callaghan DB , et al. (2019)
c.3280_3281insCC p.Gly1094AlafsTer5 frameshift_variant Familial Maternal Simplex 23160955 O'Roak BJ , et al. (2012)
c.2156dup p.Tyr719Ter frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.3047_3048insA p.Ala1017GlyfsTer6 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1222_1223del p.Lys408ValfsTer31 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.2496_2499del p.Asn832LysfsTer81 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.2497_2500del p.Lys833SerfsTer80 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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.

S

Syndromic

See all Category S Genes

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."

1/1/2021
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings2021] [Whole genome sequencing of 45 Japanese patients with intellectual disability2021]
10/1/2020
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[Expansion of the clinical phenotype associated with mutations in activity-dependent neuroprotective protein2014] [Challenges and opportunities in the investigation of unexplained intellectual disability using family-based whole-exome sequencing2015] [Novel features of Helsmoortel-Van der Aa/ADNP syndrome in a boy with a known pathogenic mutation in the ADNP gene detected by exome sequencing2017] [The Eight and a Half Year Journey of Undiagnosed AD: Gene Sequencing and Funding of Advanced Genetic Testing Has Led to Hope and New Beginnings2017] [Mutation in the ADNP gene associated with Noonan syndrome features2018] [Cellular and animal models of skin alterations in the autism-related ADNP syndrome2019] [Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
7/1/2020
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[ADNP Controls Gene Expression Through Local Chromatin Architecture by Association With BRG1 and CHD42020]
4/1/2020
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[Early behavioral and developmental interventions in ADNP-syndrome: A case report of SWI/SNF-related neurodevelopmental syndrome2020]
1/1/2020
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.2015] [Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
1S
icon
1

Score remained at 1

New Scoring Scheme
Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [Discovery of autism/intellectual disability somatic mutations in Alzheimer's brains: mutated ADNP cytoskeletal impairments and repair as a case study.2019] [New Scoring Scheme]
7/1/2019
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[Developmental Phenotype of the Rare Case of DJ Caused by a Unique ADNP Gene De Novo Mutation.2019] [Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019] [Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.2019]
4/1/2019
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome.2019] [Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.2019]
1/1/2019
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder.2018] [Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018] [Both rare and common genetic variants contribute to autism in the Faroe Islands.2019]
10/1/2018
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[Recurrent de novo mutations implicate novel genes underlying simplex autism risk.2014] [Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.2018]
7/1/2018
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A detailed clinical characterization of 78 individuals with likely disruptive ADNP mutations in Van Dijck et al., 2018 reported that autistic features were present in 93% (64/69) of individuals, with 67% reported to have a clinical diagnosis of ASD.

Reports Added
[A heterozygous microdeletion of 20q13.13 encompassing ADNP gene in a child with Helsmoortel-van der Aa syndrome.2018] [The autism spectrum phenotype in ADNP syndrome.2018]
7/1/2017
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ? 0.01, meaning that this gene had a ? 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.2017]
4/1/2017
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.2014] [The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins.2014] [Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies.2015] [The Compassionate Side of Neuroscience: Tony Sermone's Undiagnosed Genetic Journey-ADNP Mutation.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Additional data on the clinical phenotype of Helsmoortel-Van der Aa syndrome associated with a novel truncating mutation in ADNP gene.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Genome-wide characteristics of de novo mutations in autism2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Further evidence that a blepharophimosis syndrome phenotype is associated with a specific class of mutation in the ADNP gene.2017]
1/1/2017
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017]
10/1/2016
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016]
7/1/2016
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Genome-wide characteristics of de novo mutations in autism2016]
4/1/2016
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.2014] [The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins.2014] [Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies.2015] [The Compassionate Side of Neuroscience: Tony Sermone's Undiagnosed Genetic Journey-ADNP Mutation.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Additional data on the clinical phenotype of Helsmoortel-Van der Aa syndrome associated with a novel truncating mutation in ADNP gene.2016]
1/1/2016
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.2014] [The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins.2014] [Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies.2015] [The Compassionate Side of Neuroscience: Tony Sermone's Undiagnosed Genetic Journey-ADNP Mutation.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016]
7/1/2015
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.2014] [The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins.2014] [Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies.2015] [The Compassionate Side of Neuroscience: Tony Sermone's Undiagnosed Genetic Journey-ADNP Mutation.2015]
1/1/2015
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).

Reports Added
[Large-scale discovery of novel genetic causes of developmental disorders.2014] [Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies.2015]
10/1/2014
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ADNP as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760).

Reports Added
[Synaptic, transcriptional and chromatin genes disrupted in autism.2014]
7/1/2014
No data
icon
1S

Increased from No data to 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329)

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.2014] [The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism.2014] [The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins.2014]
4/1/2014
No data
icon
1S

Increased from No data to 1S

Description

Two de novo frameshift variants identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were recently identified in patients with ASD, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; probability of detecting eight or more de novo truncating events in ADNP given as P=2.65 x 10-18 in this report. The frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led the authors to conclude that ADNP mutations resulted in an autism syndrome (PMID 24531329)

Krishnan Probability Score

Score 0.61812008096142

Ranking 91/25841 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.
Original Source
ExAC Score

Score 0.9989040999292

Ranking 1089/18225 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
Original Source
Iossifov Probability Score

Score 0.955

Ranking 78/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 3.2505367123925E-5

Ranking 10/18665 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).
Original Source
Larsen Cumulative Evidence Score

Score 212

Ranking 3/461 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.
Original Source
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
2-Sep septin 2 Human Protein Binding 4735 Q15019
ADNP activity-dependent neuroprotector homeobox Human DNA Binding 23394 Q9H2P0
APOE apolipoprotein E Mouse Protein Binding 11816 P08226
ARID1A AT rich interactive domain 1A (SWI-like) Human Protein Binding 8289 O14497
CBX1 chromobox homolog 1 Human Protein Binding 10951 P83916
CBX3 chromobox homolog 3 Human Protein Binding 11335 Q13185
CBX5 chromobox homolog 5 Human Protein Binding 23468 P45973
CDC27 cell division cycle 27 Human Protein Binding 996 G3V1C4
CTSC cathepsin C Mouse Protein Binding 13032 P97821
CTSZ cathepsin Z Mouse Protein Binding 64138 Q9WUU7
EB1 Microtubule-associated protein RP/EB family member 1 Human Protein Binding 22919 Q15691
EB2 Microtubule-associated protein RP/EB family member 2 Human Protein Binding 10982 Q15555
EB3 Microtubule-associated protein RP/EB family member 3 Human Protein Binding 22924 Q9UPY8
EBNA1BP2 EBNA1 binding protein 2 Human Protein Binding 10969 H7C2Q8
EMD emerin Human Protein Binding 2010 P50402
H3F3A H3 histone, family 3A Human Protein Binding 3020 P84243
HBB hemoglobin, beta adult major chain Mouse DNA Binding 15129 P02088
HDAC1 histone deacetylase 1 Human Protein Binding 3065 Q13547
HDAC11 histone deacetylase 11 Human Protein Binding 79885 Q96DB2
HDAC7 histone deacetylase 7 Human Protein Binding 51564 Q8WUI4
MAP1LC3B microtubule-associated protein 1 light chain 3 beta Human Protein Binding 81631 Q9GZQ8
MAPRE1 microtubule-associated protein, RP/EB family, member 1 Human Protein Binding 22919 Q15691
Mapre2 microtubule-associated protein, RP/EB family, member 2 Mouse Protein Binding 212307 Q8R001
MAPRE3 microtubule-associated protein, RP/EB family, member 3 Human Protein Binding 22924 Q9UPY8
MTNR1A melatonin receptor 1A Mouse Protein Binding 17773 Q61184
MYC v-myc myelocytomatosis viral oncogene homolog (avian) Human Protein Binding 4609 P01106
MYL2 myosin, light polypeptide 2, regulatory, cardiac, slow Mouse Protein Binding 17906 P51667
NCAPH2 non-SMC condensin II complex, subunit H2 Human Protein Binding 29781 Q6IBW4
NEUROG1 neurogenin 1 Mouse Protein Binding 18014 P70660
NFIA nuclear factor I/A Human Protein Binding 4774 Q12857
PHGDH phosphoglycerate dehydrogenase Human Protein Binding 26227 O43175
POLG2 polymerase (DNA directed), gamma 2, accessory subunit Human Protein Binding NM_007215 E5KS15
QPRT Nicotinate-nucleotide pyrophosphorylase [carboxylating] Human Protein Binding 23475 Q15274
Rbfox1 RNA binding protein, fox-1 homolog (C. elegans) 1 Mouse RNA Binding 268859 Q9JJ43
RRS1 RRS1 ribosome biogenesis regulator homolog (S. cerevisiae) Human Protein Binding 23212 Q15050
SAP18 Sin3A-associated protein, 18kDa Human Protein Binding 10284 O00422
Sfpq splicing factor proline/glutamine-rich Mouse Protein Binding 71514 Q8VIJ6
SIRT7 sirtuin 7 Human Protein Binding 51547 Q9NRC8
Smarca2 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2 Mouse Protein Binding 67155 Q6DIC0
SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 Human Protein Binding 6597 A7E2E1
SMARCC2 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c, member 2 Human Protein Binding 6601 Q8TAQ2
Srcin1 SRC kinase signaling inhibitor 1 Mouse Protein Binding 56013 Q9QWI6
SUMO2 SMT3 suppressor of mif two 3 homolog 2 (S. cerevisiae) Human Protein Binding 6613 P61956
TOP3B topoisomerase (DNA) III beta Human Protein Binding 8940 O95985
Tubb2a tubulin, beta 2A class IIA Mouse Protein Binding 22151 Q7TMM9
ZNF524 Zinc finger protein 524 Human Protein Binding 147807 Q96C55
ZNF581 zinc finger protein 581 Human Protein Binding 51545 Q9P0T4
ZSCAN20 zinc finger and SCAN domain containing 20 Human Protein Binding 7579 P17040
Submit New Gene

Report an Error