Human Gene Module / Chromosome 6 / ARID1B

ARID1BAT-rich interaction domain 1B

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
36 / 73
Rare Variants / Common Variants
192 / 0
EAGLE Score
34.75
Strong Learn More
Aliases
ARID1B, RP11-419L10.1,  6A3-5,  BAF250B,  BRIGHT,  DAN15,  ELD/OSA1,  KIAA1235,  MRD12,  OSA2,  P250R
Associated Syndromes
Coffin-Siris syndrome, Coffin-Siris syndrome, DD/ID, Coffin-Siris syndrome 1, DD, Coffin-Siris syndrome, DD
Chromosome Band
6q25.3
Associated Disorders
DD/NDD, ADHD, ID, EP, EPS, ASD
Genetic Category
Rare Single Gene Mutation, Syndromic, Functional
Relevance to Autism

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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 ARID1B as a gene reaching exome-wide significance (P < 2.5E-06). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Molecular Function

This locus encodes an AT-rich DNA interacting domain-containing protein. The encoded protein is a component of the SWI/SNF chromatin remodeling complex and may play a role in cell-cycle activation. The protein encoded by this locus is similar to AT-rich interactive domain-containing protein 1A. These two proteins function as alternative, mutually exclusive ARID-subunits of the SWI/SNF complex. The associated complexes play opposing roles.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBase
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ARID1B (73 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Reduced transcript expression of genes affected by inherited and de novo CNVs in autism Nord AS , et al. (2011) Yes -
2 Recent Recommendation Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B Halgren C , et al. (2011) Yes ID
3 Support Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability Hoyer J , et al. (2012) No Autistic features
4 Support Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome Tsurusaki Y , et al. (2012) No -
5 Support Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome Santen GW , et al. (2012) No ID, ASD
6 Support Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
7 Support Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders O'Roak BJ , et al. (2012) Yes -
8 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
9 Support Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene Vals MA , et al. (2014) No ID, autistic features
10 Support Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency Sim JC , et al. (2014) No -
11 Support De novo mutations in moderate or severe intellectual disability Hamdan FF , et al. (2014) No Speech delay, hypotonia
12 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
13 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) Yes -
14 Support Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
15 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
16 Support Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
17 Support Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms D'Gama AM , et al. (2015) Yes -
18 Recent Recommendation Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA Turner TN et al. (2016) Yes -
19 Support Comprehensive molecular testing in patients with high functioning autism spectrum disorder Alvarez-Mora MI , et al. (2016) Yes -
20 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
21 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing Martnez F , et al. (2016) No ID
22 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
23 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
24 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families Trujillano D , et al. (2016) No ADHD
25 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases Stessman HA , et al. (2017) Yes -
26 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
27 Support The HHID syndrome of hypertrichosis, hyperkeratosis, abnormal corpus callosum, intellectual disability, and minor anomalies is caused by mutations in ARID1B Zweier M , et al. (2017) No -
28 Support Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability Zahir FR , et al. (2017) Yes -
29 Support Genomic diagnosis for children with intellectual disability and/or developmental delay Bowling KM , et al. (2017) No Epilepsy/seizures
30 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 Coffin-Siris syndrome
31 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
32 Support Expanding the genetic heterogeneity of intellectual disability Anazi S , et al. (2017) No -
33 Support Genomic Patterns of De Novo Mutation in Simplex Autism Turner TN et al. (2017) Yes -
34 Support High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies Hamdan FF , et al. (2017) No DD/ID
35 Support Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice Tumien B , et al. (2017) No -
36 Support Risks and Recommendations in Prenatally Detected De Novo Balanced Chromosomal Rearrangements from Assessment of Long-Term Outcomes Halgren C , et al. (2018) Yes -
37 Support A 69-year-old woman with Coffin-Siris syndrome Mttnen L , et al. (2018) No DD, ID, autistic behavior
38 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes Guo H , et al. (2018) Yes -
39 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
40 Support Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population Monies D , et al. (2019) No ADHD, OCD, epilepsy/seizures
41 Support Characterization of intellectual disability and autism comorbidity through gene panel sequencing Aspromonte MC , et al. (2019) Yes -
42 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
43 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 -
44 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
45 Support Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort Wu H , et al. (2019) Yes Macrocephaly
46 Support De Novo ARID1B mutations cause growth delay associated with aberrant Wnt/?-catenin signaling Liu X , et al. (2020) 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 Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability Chevarin M et al. (2020) No Marfanoid habitus
49 Support Coffin-Siris Syndrome-1: Report of five cases from Asian populations with truncating mutations in the ARID1B gene Lian S et al. (2020) No -
50 Support A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders Suzuki T et al. (2020) No -
51 Support - Rodin RE et al. (2021) Yes -
52 Support - Moffat JJ et al. (2021) No -
53 Support - Brunet T et al. (2021) No -
54 Support - Hiraide T et al. (2021) No ASD
55 Support - Cheng SSW et al. (2021) No ASD, epilepsy/seizures
56 Support - Miyamoto S et al. (2021) No ASD, DD, ID, epilepsy/seizures
57 Support - Pode-Shakked B et al. (2021) No ASD, epilepsy/seizures
58 Support - Mahjani B et al. (2021) Yes -
59 Support - Lee Y et al. (2021) No ID, epilepsy/seizures, Afs
60 Support - Lu G et al. (2021) No Epilepsy/seizures
61 Support - Xiang J et al. (2021) No -
62 Recent Recommendation - Paulsen B et al. (2022) Yes -
63 Support - Woodbury-Smith M et al. (2022) Yes -
64 Support - Verberne EA et al. (2022) No -
65 Support - Wang Q et al. (2022) No -
66 Support - England) (02/1) Yes -
67 Support - Hu C et al. (2022) Yes -
68 Support - Sofronova V et al. (2022) No -
69 Support - Zhou X et al. (2022) Yes -
70 Recent Recommendation - Kundishora AJ et al. (2023) No ASD, DD, epilepsy/seizures
71 Support - Spataro N et al. (2023) No -
72 Recent Recommendation - Timberlake AT et al. (2023) No ASD
73 Support - Doldur-Balli F et al. (2023) No -
Rare Variants   (192)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - - 34706719 Lee Y et al. (2021)
- - copy_number_loss De novo NA - 24674232 Sim JC , et al. (2014)
- - translocation De novo NA - 21801163 Halgren C , et al. (2011)
- - translocation De novo NA - 29805044 Halgren C , et al. (2018)
- - copy_number_loss De novo NA - 21448237 Nord AS , et al. (2011)
- - copy_number_gain De novo NA - 22405089 Hoyer J , et al. (2012)
- - copy_number_loss De novo NA - 21801163 Halgren C , et al. (2011)
- - copy_number_loss De novo NA Simplex 34775996 Lu G et al. (2021)
delG - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
c.-167G>A - splice_site_variant De novo NA - 34775996 Lu G et al. (2021)
- - copy_number_loss De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.73C>T p.Gln25Ter stop_gained De novo NA - 34706719 Lee Y et al. (2021)
c.846+1G>A - splice_site_variant De novo NA - 34706719 Lee Y et al. (2021)
c.1562G>A p.Ser521Asn missense_variant Unknown - - 35699097 England) (02/1)
c.2170C>T p.Gln724Ter missense_variant Unknown - - 35699097 England) (02/1)
c.2176G>A p.Gly726Arg missense_variant Unknown - - 35699097 England) (02/1)
c.2377G>A p.Asp793Asn missense_variant Unknown - - 35699097 England) (02/1)
c.2846A>G p.Asn949Ser missense_variant Unknown - - 35699097 England) (02/1)
c.1986C>A p.Tyr662Ter stop_gained De novo NA - 35741772 Hu C et al. (2022)
c.403C>T p.Arg135Ter stop_gained De novo NA - 34706719 Lee Y et al. (2021)
c.-42C>T - stop_gained De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.3209A>G p.Gln1070Arg missense_variant Unknown - - 35699097 England) (02/1)
c.3644G>A p.Ser1215Asn missense_variant Unknown - - 35699097 England) (02/1)
c.3838G>A p.Glu1280Lys missense_variant Unknown - - 35699097 England) (02/1)
c.3887C>G p.Ala1296Gly missense_variant Unknown - - 35699097 England) (02/1)
c.1311C>G p.Gly437%3D stop_gained De novo NA - 34706719 Lee Y et al. (2021)
c.1861C>T p.Gln621Ter stop_gained De novo NA - 34706719 Lee Y et al. (2021)
c.2719C>T p.Gln907Ter stop_gained De novo NA - 34706719 Lee Y et al. (2021)
c.1174C>T p.Arg392Ter stop_gained De novo NA - 32339967 Lian S et al. (2020)
c.2086C>T p.Gln696Ter stop_gained De novo NA - 32339967 Lian S et al. (2020)
c.2941C>T p.Gln981Ter stop_gained De novo NA - 24674232 Sim JC , et al. (2014)
c.4194T>G p.Tyr1398Ter stop_gained De novo NA - 34858471 Xiang J et al. (2021)
c.1762G>T p.Glu588Ter stop_gained De novo NA - 33432195 Rodin RE et al. (2021)
c.4378C>T p.Arg1460Ter stop_gained Unknown - - 34615535 Mahjani B et al. (2021)
- - copy_number_loss Familial Maternal Simplex 26749308 Turner TN et al. (2016)
c.3304C>T p.Arg1102Ter stop_gained De novo NA - 22405089 Hoyer J , et al. (2012)
c.3919C>T p.Pro1307Ser stop_gained De novo NA - 22405089 Hoyer J , et al. (2012)
c.4038T>A p.Tyr1346Ter stop_gained De novo NA - 22405089 Hoyer J , et al. (2012)
c.2611C>T p.Gln871Ter stop_gained De novo NA Simplex 34775996 Lu G et al. (2021)
c.1109T>C p.Met370Thr missense_variant De novo NA - 35982159 Zhou X et al. (2022)
c.1147G>A p.Val383Met missense_variant De novo NA - 35982159 Zhou X et al. (2022)
c.1256T>C p.Leu419Pro missense_variant De novo NA - 35982159 Zhou X et al. (2022)
c.1339G>A p.Glu447Lys missense_variant De novo NA - 35982159 Zhou X et al. (2022)
A>G p.? splice_site_variant Familial - Multiplex 28263302 C Yuen RK et al. (2017)
c.4741C>T p.Gln1581Ter stop_gained De novo NA - 27620904 Martnez F , et al. (2016)
c.2242C>T p.Gln748Ter stop_gained De novo NA - 28554332 Bowling KM , et al. (2017)
c.1888-2A>G - splice_site_variant De novo NA - 28191889 Stessman HA , et al. (2017)
c.3012C>A p.Asn1004Lys missense_variant De novo NA - 35982159 Zhou X et al. (2022)
c.6533G>A p.Trp2178Ter missense_variant De novo NA - 35982159 Zhou X et al. (2022)
c.4845G>T p.Leu1615= stop_gained De novo NA Unknown 31981384 Liu X , et al. (2020)
c.6100C>T p.Gln2034Ter stop_gained De novo NA - 28554332 Bowling KM , et al. (2017)
c.2318C>G p.Ser773Ter stop_gained De novo NA - 27479843 Lelieveld SH et al. (2016)
c.2653C>T p.Arg885Ter stop_gained De novo NA - 28191889 Stessman HA , et al. (2017)
c.1063A>T p.Asn355Tyr missense_variant Familial Paternal - 35699097 England) (02/1)
c.2528C>T p.Pro843Leu stop_gained De novo NA Simplex 30504930 Guo H , et al. (2018)
c.2536C>T p.Gln846Ter stop_gained De novo NA Simplex 30504930 Guo H , et al. (2018)
c.1831C>T p.Pro611Ser stop_gained De novo NA Simplex 31981384 Liu X , et al. (2020)
c.3678G>T p.Ser1226= stop_gained Unknown - Simplex 28263302 C Yuen RK et al. (2017)
c.4566T>A p.Tyr1522Ter stop_gained De novo NA - 27479843 Lelieveld SH et al. (2016)
c.6511C>T p.Gln2171Ter stop_gained De novo NA - 27479843 Lelieveld SH et al. (2016)
c.3424C>T p.Arg1142Ter stop_gained De novo NA - 28191889 Stessman HA , et al. (2017)
c.5366G>A p.Ser1789Asn missense_variant Familial Paternal - 35699097 England) (02/1)
c.6683C>A p.Ser2228Ter stop_gained De novo NA Simplex 31981384 Liu X , et al. (2020)
c.4230G>A p.Pro1410= splice_site_variant Unknown - - 29286531 Tumien B , et al. (2017)
c.3670+36G>A - missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.592C>T p.Gln198Ter stop_gained Unknown Not maternal - 32339967 Lian S et al. (2020)
c.4230G>A p.Pro1410= splice_site_variant De novo NA - 22405089 Hoyer J , et al. (2012)
c.403C>T p.Arg135Ter stop_gained De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.1762G>T p.Gly588Cys stop_gained Familial - Simplex 28263302 C Yuen RK et al. (2017)
c.-252-1G>A - splice_site_variant De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.6010G>T p.Glu2004Ter stop_gained De novo NA - 31209962 Aspromonte MC , et al. (2019)
c.5830C>T p.Pro1944Ser stop_gained Familial Paternal - 28708303 Chrot E , et al. (2017)
c.5911G>T p.Glu1971Ter stop_gained De novo NA Simplex 28940097 Anazi S , et al. (2017)
c.6382C>T p.Arg2128Ter stop_gained De novo NA Simplex 33619735 Brunet T et al. (2021)
c.4009C>T p.Arg1337Ter stop_gained De novo NA Unknown 33619735 Brunet T et al. (2021)
c.4110G>A p.Pro1370= splice_site_variant De novo NA - 28323383 Zweier M , et al. (2017)
c.1729C>T p.Gln577Ter stop_gained De novo NA Simplex 28263302 C Yuen RK et al. (2017)
c.2528C>A p.Ser843Ter stop_gained De novo NA Simplex 33644862 Hiraide T et al. (2021)
c.2406G>A p.Trp802Ter stop_gained De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.5026G>A p.Ala1676Thr splice_site_variant De novo NA - 28708303 Chrot E , et al. (2017)
c.1980G>A p.Pro660%3D splice_site_variant De novo NA - 36980980 Spataro N et al. (2023)
c.3646C>T p.Arg1216Ter stop_gained De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.4252C>T p.Arg1418Ter stop_gained De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.6274C>T p.Pro2092Ser stop_gained De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.1999-4542C>A - intergenic_variant De novo NA Simplex 26749308 Turner TN et al. (2016)
c.6410A>C p.Asp2137Ala missense_variant De novo NA - 31452935 Feliciano P et al. (2019)
c.3214T>C p.Ser1072Pro missense_variant De novo NA Simplex 31674007 Wu H , et al. (2019)
c.2132A>G p.Gln711Arg missense_variant De novo NA Simplex 35982159 Zhou X et al. (2022)
c.2986+1G>C p.? splice_site_variant De novo NA Simplex 33644862 Hiraide T et al. (2021)
c.3223C>T p.Arg1075Ter stop_gained De novo NA Simplex 22426309 Santen GW , et al. (2012)
c.5329A>T p.Lys1777Ter stop_gained De novo NA Simplex 22426309 Santen GW , et al. (2012)
c.2206C>T p.Gln736Ter stop_gained De novo NA Simplex 35879281 Sofronova V et al. (2022)
c.3227del p.Lys1076SerfsTer4 frameshift_variant De novo NA - 34706719 Lee Y et al. (2021)
c.188_193del p.Asp63_Gly64del inframe_deletion De novo NA - 35982159 Zhou X et al. (2022)
c.2977C>T p.Gln993Ter stop_gained De novo NA Simplex 25363760 De Rubeis S , et al. (2014)
c.2938C>T p.Gln980Ter stop_gained De novo NA Simplex 28191889 Stessman HA , et al. (2017)
c.1704T>G p.Ala568%3D synonymous_variant De novo NA Simplex 35982159 Zhou X et al. (2022)
c.3208_3209del p.Ser1070Ter frameshift_variant De novo NA - 24674232 Sim JC , et al. (2014)
c.6475G>A p.Val2159Ile missense_variant De novo NA Simplex 28714951 Lim ET , et al. (2017)
c.4286G>A p.Gly1429Glu missense_variant Unknown - Simplex 31130284 Monies D , et al. (2019)
c.6707T>C p.Leu2236Ser missense_variant Unknown - Unknown 31130284 Monies D , et al. (2019)
c.1463C>G p.Pro488Arg missense_variant Unknown - Unknown 26637798 D'Gama AM , et al. (2015)
c.3020C>A p.Ser1007Ter stop_gained De novo NA Simplex 25363760 De Rubeis S , et al. (2014)
c.4645C>T p.Pro1549Ser missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.4496del p.Met1499ArgfsTer72 frameshift_variant De novo NA - 35982159 Zhou X et al. (2022)
c.1137del p.Leu380CysfsTer40 splice_site_variant De novo NA - 35982159 Zhou X et al. (2022)
c.5015A>G p.Asn1672Ser missense_variant De novo NA Simplex 25961944 Krumm N , et al. (2015)
c.4144del p.Tyr1382MetfsTer106 frameshift_variant De novo NA - 32339967 Lian S et al. (2020)
c.2181G>A p.Met727Ile synonymous_variant De novo NA Multiplex 35982159 Zhou X et al. (2022)
c.4274dup p.Arg1426AlafsTer73 frameshift_variant De novo NA - 24674232 Sim JC , et al. (2014)
- p.Leu2049TrpfsTer50 frameshift_variant De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.1702G>A p.Gly568Arg missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2404T>C p.Ser802Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2939A>T p.Gln980Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4129C>T p.Arg1377Ter stop_gained De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.5551G>T p.Glu1851Ter stop_gained De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.872_890del p.Leu291ArgfsTer52 frameshift_variant De novo NA - 35982159 Zhou X et al. (2022)
c.1114dup p.Arg372ProfsTer163 frameshift_variant De novo NA - 22405089 Hoyer J , et al. (2012)
c.5855T>C p.Val1952Ala missense_variant De novo NA Simplex 32277047 Chevarin M et al. (2020)
c.6122A>C p.His2041Pro missense_variant De novo NA Simplex 33958710 Miyamoto S et al. (2021)
c.3254C>T p.Pro1085Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.5734del p.Ile1912Ter frameshift_variant De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.2333-2A>C - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.4110G>A p.Pro1370= splice_site_variant De novo NA Simplex 31406558 Munnich A , et al. (2019)
c.1206_1224del p.Ser403GlufsTer43 frameshift_variant De novo NA - 35982159 Zhou X et al. (2022)
c.2056G>A p.Ala686Thr missense_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
c.5903A>G p.Glu1968Gly missense_variant De novo NA Simplex 25363760 De Rubeis S , et al. (2014)
c.1402_1409del p.Gly468ArgfsTer147 frameshift_variant De novo NA - 32339967 Lian S et al. (2020)
c.3220G>A p.Asp1074Asn missense_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
c.1810del p.Met604TrpfsTer2 frameshift_variant De novo NA Simplex 35266334 Wang Q et al. (2022)
c.1331del p.Ser444CysfsTer8 frameshift_variant De novo NA Simplex 35982159 Zhou X et al. (2022)
c.4133G>A p.Arg1378Lys splice_site_variant Familial - Multiplex 28263302 C Yuen RK et al. (2017)
c.2231C>T p.Ala744Val missense_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.5032_5035del p.Arg1678Ter frameshift_variant Unknown - Unknown 31130284 Monies D , et al. (2019)
c.5072del p.Ser1691IlefsTer33 frameshift_variant De novo NA - 27479843 Lelieveld SH et al. (2016)
c.3326_3327del p.Arg1109LysfsTer48 frameshift_variant De novo NA - 22405089 Hoyer J , et al. (2012)
c.6463_6473del p.Leu2155ArgfsTer73 frameshift_variant De novo NA - 22405089 Hoyer J , et al. (2012)
c.1584del p.Leu528PhefsTer62 frameshift_variant De novo NA Simplex 24569609 Vals MA , et al. (2014)
c.1990del p.Ser664ValfsTer20 frameshift_variant De novo NA Simplex 32530565 Suzuki T et al. (2020)
c.5376_5379del p.Ser1792ArgfsTer13 frameshift_variant De novo NA - 28323383 Zweier M , et al. (2017)
c.2782_2785del p.Arg928Ter frameshift_variant De novo NA Simplex 32277047 Chevarin M et al. (2020)
c.1595del p.Gly532AlafsTer58 frameshift_variant De novo NA Simplex 28539120 Zahir FR , et al. (2017)
c.1504del p.Ser502AlafsTer21 frameshift_variant De novo NA Simplex 28965761 Turner TN et al. (2017)
c.2131del p.Gln711SerfsTer27 frameshift_variant De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.6700_6701del p.Phe2234LeufsTer6 frameshift_variant De novo NA - 35253369 Verberne EA et al. (2022)
c.3118del p.Glu1040LysfsTer16 frameshift_variant De novo NA Simplex 33644862 Hiraide T et al. (2021)
c.4466del p.Tyr1489SerfsTer82 frameshift_variant De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.6091dup p.Gln2031ProfsTer36 frameshift_variant De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.1832del p.Leu611CysfsTer65 frameshift_variant De novo NA Simplex 33958710 Miyamoto S et al. (2021)
c.1880C>T p.Pro627Leu missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2258C>T p.Pro753Leu missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4395del p.Tyr1467ThrfsTer21 frameshift_variant Unknown Not paternal - 27824329 Wang T , et al. (2016)
c.5509del p.Leu1837CysfsTer54 frameshift_variant De novo NA Simplex 22495309 O'Roak BJ , et al. (2012)
c.3706dup p.Gln1236ProfsTer14 frameshift_variant De novo NA Simplex 23160955 O'Roak BJ , et al. (2012)
c.3716del p.Gly1239AlafsTer12 frameshift_variant De novo NA Simplex 25356899 Hamdan FF , et al. (2014)
c.6764del p.Phe2255SerfsTer17 frameshift_variant De novo NA Simplex 29100083 Hamdan FF , et al. (2017)
c.5228_5231del p.Val1743GlufsTer62 frameshift_variant De novo NA - 28191889 Stessman HA , et al. (2017)
c.3791T>G p.Met1264Arg missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4097G>A p.Arg1366His missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4211A>G p.Tyr1404Cys missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2231_2232dup p.Pro745AsnfsTer7 frameshift_variant De novo NA Unknown 33619735 Brunet T et al. (2021)
c.5063_5064dup p.Ala1689TrpfsTer36 frameshift_variant Unknown - Simplex 30055038 Mttnen L , et al. (2018)
c.5547dup p.Gln1850AlafsTer5 frameshift_variant De novo NA Simplex 27848944 Trujillano D , et al. (2016)
c.6023_6031dup p.Ala2010_Leu2011insSerGlyAla inframe_insertion De novo NA - 35982159 Zhou X et al. (2022)
c.2020_2023del p.Gly674ThrfsTer63 frameshift_variant De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.6377dup p.Val2128GlyfsTer7 frameshift_variant De novo NA Simplex 34580403 Pode-Shakked B et al. (2021)
c.2306delinsTCCGCAGCCACT p.Ser769IlefsTer67 frameshift_variant De novo NA - 24674232 Sim JC , et al. (2014)
c.4620_4629del p.Met1540IlefsTer4 frameshift_variant De novo NA Simplex 22426309 Santen GW , et al. (2012)
c.5148_5434del p.Gly1717MetfsTer4 frameshift_variant De novo NA Simplex 33958710 Miyamoto S et al. (2021)
c.736G>A p.Gly246Ser missense_variant Unknown Not paternal Simplex 26845707 Alvarez-Mora MI , et al. (2016)
c.5235_5236insG p.Pro1746AlafsTer7 frameshift_variant De novo NA Simplex 25363760 De Rubeis S , et al. (2014)
c.2642_2645de p.Arg881ThrfsTer46 frameshift_variant De novo NA Simplex 34580403 Pode-Shakked B et al. (2021)
c.5376_5379del p.Ser1792ArgfsTer13 frameshift_variant De novo NA Simplex 27848944 Trujillano D , et al. (2016)
c.1621C>T p.Gln541Ter stop_gained De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1729C>T p.Gln577Ter stop_gained De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1914C>A p.Tyr638Ter stop_gained De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.3286_3287del p.Leu1096AlafsTer21 frameshift_variant De novo NA Simplex 34580403 Pode-Shakked B et al. (2021)
c.4045C>T p.Gln1349Ter stop_gained De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.5404C>T p.Arg1802Ter stop_gained De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.5776C>T p.Arg1926Ter stop_gained De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.3809_3810insATGCTCAT p.Tyr1271CysfsTer66 frameshift_variant De novo NA Simplex 33768696 Cheng SSW et al. (2021)
c.122C>T p.Ser41Phe missense_variant Familial Paternal Multi-generational 26845707 Alvarez-Mora MI , et al. (2016)
c.6726_6730del p.Gly2243SerfsTer70 frameshift_variant Familial Maternal Multiplex 33768696 Cheng SSW et al. (2021)
c.4237C>T p.Pro1413Ser missense_variant Unknown - Multiplex or multi-generational 26637798 D'Gama AM , et al. (2015)
c.736G>A p.Gly246Ser missense_variant Familial Paternal Multi-generational 26845707 Alvarez-Mora MI , et al. (2016)
c.4894G>A p.Val1632Ile splice_site_variant De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.2507C>G p.Pro836Arg stop_gained De novo NA Multi-generational 25533962 Deciphering Developmental Disorders Study (2014)
c.6562del p.Ala2188ProfsTer2 frameshift_variant De novo NA Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.2496G>T p.Gln832His missense_variant De novo NA Multi-generational 25533962 Deciphering Developmental Disorders Study (2014)
c.4144del p.Tyr1382MetfsTer106 frameshift_variant De novo NA Multiplex 25533962 Deciphering Developmental Disorders Study (2014)
c.5267_5270del p.Ala1756GlyfsTer49 frameshift_variant De novo NA 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."

4/1/2021
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[Genotype and phenotype in 18 Chinese patients with Coffin-Siris syndrome2021] [Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies2021]
1/1/2021
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing2021] [Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex2021] [De novo variants in neurodevelopmental disorders-experiences from a tertiary care center2021] [Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing2021]
7/1/2020
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders2020]
4/1/2020
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability2020] [Coffin-Siris Syndrome-1: Report of five cases from Asian populations with truncating mutations in the ARID1B gene2020]
1/1/2020
1
icon
1

Score remained at 1

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.2015] [De Novo ARID1B mutations cause growth delay associated with aberrant Wnt/-catenin signaling.2020] [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 the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.2019] [New Scoring Scheme]
7/1/2019
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019] [Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019] [Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019] [Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.2019]
1/1/2019
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018]
10/1/2018
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[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 the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[A 69-year-old woman with Coffin-Siris syndrome.2018]
10/1/2017
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[Expanding the genetic heterogeneity of intellectual disability.2017] [Genomic Patterns of De Novo Mutation in Simplex Autism2017] [High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.2017]
7/1/2017
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants in the ARID1B gene were identified by exome sequencing in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Nord et al., 2011 (PMID 21448237) had previously identified a de novo deletion within the ARID1B gene resulting in reduced transcript expression in a patient with autism, and a de novo translocation and deletions disrupting ARID1B had previously been identified in ASD patients in Halgren et al., 2011 (PMID 21801163). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014. Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC in this report identified ARID1B 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). Variants in ARID1B are also responsible for Coffin-Siris syndrome (CSS); a subset of CSS patients have been reported to show ASD or autistic features (PMIDs 22426309, 24569609).

Reports Added
[Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.2017] [Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.2017]
4/1/2017
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC identified ARID1B 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
[Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [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 discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B.2011] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome.2012] [Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene.2014] [Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability.2012] [Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency.2014] [Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome.2012] [Excess of rare, inherited truncating mutations in autism.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] [Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA2016] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [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] [The HHID syndrome of hypertrichosis, hyperkeratosis, abnormal corpus callosum, intellectual disability, and minor anomalies is caused by mutations ...2017] [De novo mutations in moderate or severe intellectual disability.2014] [Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]
1/1/2017
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC identified ARID1B 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 reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC identified ARID1B 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
[High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [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 reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC identified ARID1B 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]
1/1/2016
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC identified ARID1B 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
[Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [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 discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B.2011] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome.2012] [Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene.2014] [Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability.2012] [Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency.2014] [Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome.2012] [Excess of rare, inherited truncating mutations in autism.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] [Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA2016] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016]
4/1/2015
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC identified ARID1B 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
[Excess of rare, inherited truncating mutations in autism.2015]
1/1/2015
1S
icon
1S

Score remained at 1S

Description

Two de novo frameshift variants reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC identified ARID1B 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]
10/1/2014
3S
icon
1S

Decreased from 3S to 1S

Description

Two de novo frameshift variants reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609). Three additional de novo loss-of-function variants in ARID1B were identified in ASD probands from the Autism Sequencing Consortium (ASC). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from ASC identified ARID1B 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
3S

Increased from No data to 3S

Description

Two de novo frameshift variants reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609)

4/1/2014
No data
icon
3S

Increased from No data to 3S

Description

Two de novo frameshift variants reported in unrelated simplex ASD cases (PMIDs 22495309 and 23160955); de novo translocation and deletions disrupting ARID1B identified in ASD patients (PMID 21801163). Variants in ARID1B recently found to be associated with Coffin-Siris syndrome (CSS); a subset of CSS patients also show ASD or autistic features (PMID 22426309, PMID 24569609)

Reports Added
[Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency.2014]
Krishnan Probability Score

Score 0.49277830741014

Ranking 4408/25841 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 0.99994993020041

Ranking 585/18225 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 0.991

Ranking 23/239 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 1.539076378565E-7

Ranking 3/18665 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 78

Ranking 14/461 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
Zhang D Score

Score 0.52142411492117

Ranking 378/20870 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.
Original Source
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
BCL7A B-cell CLL/lymphoma 7A Human Protein Binding 605 Q4VC05
BCL7C B-cell CLL/lymphoma 7 protein family member C Human Protein Binding 9274 Q8WUZ0-2
DPF2 D4, zinc and double PHD fingers family 2 Human Protein Binding 5977 Q92785
DPF3 D4, zinc and double PHD fingers, family 3 Human Protein Binding 8110 Q92784
HIST2H2BE histone cluster 2, H2be Human Protein Modification 8349 Q16778
NAGK N-acetylglucosamine kinase Human Protein Binding 55577 Q9UJ70
PRMT5 protein arginine methyltransferase 5 Human Protein Binding 10419 O14744
SMARCB1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1 Human Protein Binding 6598 Q12824
SMARCC1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c, member 1 Human Protein Binding 6599 Q58EY4
SMARCD1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1 Human Protein Binding 6602 Q96GM5
SMARCE1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1 Human Protein Binding 6605 Q969G3
SS18 synovial sarcoma translocation, chromosome 18 Human Protein Binding 6760 Q15532
TCEB1 transcription elongation factor B (SIII), polypeptide 1 (15kDa, elongin C) Human Protein Binding 6921 Q15369
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