Human Gene Module / Chromosome 6 / ARID1B

ARID1BAT-rich interaction domain 1B

Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
20 / 35
Rare Variants / Common Variants
94 / 0
Aliases
ARID1B, RP11-419L10.1,  6A3-5,  BAF250B,  BRIGHT,  DAN15,  ELD/OSA1,  KIAA1235,  MRD12,  OSA2,  P250R
Associated Syndromes
Coffin-Siris syndrome
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
6q25.3
Associated Disorders
ASD, DD/NDD, EPS, ADHD, ID, EP
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). 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.

Reports related to ARID1B (35 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 (1 case)
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 (1 case)
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 Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms. D'Gama AM , et al. (2015) Yes -
17 Recent recommendation Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA. Turner TN , et al. (2016) Yes -
18 Support Comprehensive molecular testing in patients with high functioning autism spectrum disorder. Alvarez-Mora MI , et al. (2016) Yes -
19 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Lelieveld SH , et al. (2016) No -
20 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing. Martnez F , et al. (2016) No ID
21 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior. Doan RN , et al. (2016) Yes -
22 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
23 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Trujillano D , et al. (2016) No ADHD (1/2 cases)
24 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Stessman HA , et al. (2017) Yes -
25 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
26 Support The HHID syndrome of hypertrichosis, hyperkeratosis, abnormal corpus callosum, intellectual disability, and minor anomalies is caused by mutations ... Zweier M , et al. (2017) No -
27 Support Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability. Zahir FR , et al. (2017) Yes -
28 Support Genomic diagnosis for children with intellectual disability and/or developmental delay. Bowling KM , et al. (2017) No Epilepsy/seizures
29 Support Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients. Chrot E , et al. (2017) No Coffin-Siris syndrome (1/2 cases)
30 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Lim ET , et al. (2017) Yes -
31 Support Expanding the genetic heterogeneity of intellectual disability. Anazi S , et al. (2017) No -
32 Support Genomic Patterns of De Novo Mutation in Simplex Autism. Turner TN , et al. (2017) Yes -
33 Support High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies. Hamdan FF , et al. (2017) No DD/ID
34 Support Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice. Tumien B , et al. (2017) No -
35 Support Risks and Recommendations in Prenatally Detected De Novo Balanced Chromosomal Rearrangements from Assessment of Long-Term Outcomes. Halgren C , et al. (2018) Yes -
Rare Variants   (94)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 21448237 Nord AS , et al. (2011)
- - translocation De novo - - 21801163 Halgren C , et al. (2011)
- - copy_number_loss De novo - - 21801163 Halgren C , et al. (2011)
- - copy_number_loss De novo - - 21801163 Halgren C , et al. (2011)
- - copy_number_loss De novo - - 21801163 Halgren C , et al. (2011)
- - copy_number_gain De novo - - 22405089 Hoyer J , et al. (2012)
c.3919C>T p.Gln1307Ter stop_gained De novo - - 22405089 Hoyer J , et al. (2012)
c.6463_6473del p.Ser2155LeufsTer33 frameshift_variant De novo - - 22405089 Hoyer J , et al. (2012)
c.3304C>T p.Arg1102Ter stop_gained De novo - - 22405089 Hoyer J , et al. (2012)
c.3323_3324delAA p.Lys1108ArgfsTer9 frameshift_variant De novo - - 22405089 Hoyer J , et al. (2012)
c.4110G>A p.Arg1338ArgfsTer9 splice_site_variant De novo - - 22405089 Hoyer J , et al. (2012)
c.4038T>A p.Tyr1346Ter stop_gained De novo - - 22405089 Hoyer J , et al. (2012)
c.1114dupC p.Arg372ProfsTer163 frameshift_variant De novo - - 22405089 Hoyer J , et al. (2012)
c.5329A>T p.Lys1777Ter stop_gained De novo - Simplex 22426309 Santen GW , et al. (2012)
c.3223C>T p.Arg1075Ter stop_gained De novo - Simplex 22426309 Santen GW , et al. (2012)
c.4619_4628del p.Gln1541ArgfsTer35 frameshift_variant De novo - Simplex 22426309 Santen GW , et al. (2012)
del(TGTT) p.Phe1798LeufsTer52 frameshift_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
ins(C) p.Gln1196ProfsTer14 frameshift_variant De novo - Simplex 23160955 O'Roak BJ , et al. (2012)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
c.1584delG p.Leu528PhefsTer65 frameshift_variant De novo - Simplex 24569609 Vals MA , et al. (2014)
- - copy_number_loss De novo - - 24674232 Sim JC , et al. (2014)
c.3208_3209delAA p.Lys1070AlafsTer47 frameshift_variant De novo - - 24674232 Sim JC , et al. (2014)
c.2306_2308delCCGinsTCCGCAGCCACTCC p.Pro769LeufsTer17 frameshift_variant De novo - - 24674232 Sim JC , et al. (2014)
c.4273dupT p.Tyr1425LeufsTer34 frameshift_variant De novo - - 24674232 Sim JC , et al. (2014)
c.2941C>T p.Gln981Ter stop_gained De novo - - 24674232 Sim JC , et al. (2014)
c.3716delC p.Pro1239HisfsTer5 frameshift_variant De novo - Simplex 25356899 Hamdan FF , et al. (2014)
c.2977C>T p.Gln993Ter stop_gained De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.3020C>A p.Ser1007Ter stop_gained De novo - Simplex 25363760 De Rubeis S , et al. (2014)
ins(G) - frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.5903A>G p.His1968Arg missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.3923G>A p.Arg1308His missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3791T>G p.Phe1264Cys missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4211A>G p.Gln1404Arg missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.368C>T p.Pro123Leu missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.410C>T p.Pro137Leu missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1528G>A p.Gly510Arg missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2810A>T p.Gln397Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.556T>C p.Ser186Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.748G>A p.Ala250Thr missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3254C>T p.Pro1085Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.5404C>T p.Arg1802Ter stop_gained De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1914C>A p.Tyr638Ter stop_gained De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.6560delT p.Leu2187ArgfsTer6 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.5776C>T p.Arg1926Ter stop_gained De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.4045C>T p.Gln1349Ter stop_gained De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.4895-1G>A - splice_site_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1621C>T p.Gln541Ter stop_gained De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.2496G>T p.Gln832His missense_variant De novo - Multi-generational 25533962 Deciphering Developmental Disorders Study (2014)
c.2507C>G p.Ser836Ter stop_gained De novo - Multi-generational 25533962 Deciphering Developmental Disorders Study (2014)
c.5265_5270delAGAAAGinsAG p.Glu1756AlafsTer9 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.4144_4148delCCCCCinsCCCC p.Pro1383GlnfsTer65 frameshift_variant De novo - Multiplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1729C>T p.Gln577Ter stop_gained De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.5015A>G p.Asn1672Ser missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.4237C>T p.Pro1413Ser missense_variant Unknown - Multiplex or multi-generational 26637798 D'Gama AM , et al. (2015)
c.1463C>G p.Pro488Arg missense_variant Unknown - Unknown 26637798 D'Gama AM , et al. (2015)
- - copy_number_loss Familial Maternal Simplex 26749308 Turner TN , et al. (2016)
- - intergenic_variant De novo - Simplex 26749308 Turner TN , et al. (2016)
c.736G>A p.Gly246Ser missense_variant Familial Paternal Multi-generational 26845707 Alvarez-Mora MI , et al. (2016)
c.736G>A p.Gly246Ser missense_variant Unknown Not paternal Simplex 26845707 Alvarez-Mora MI , et al. (2016)
c.736G>A p.Gly246Ser missense_variant Familial Paternal Multi-generational 26845707 Alvarez-Mora MI , et al. (2016)
- p.Ser41Phe missense_variant Familial Paternal Multi-generational 26845707 Alvarez-Mora MI , et al. (2016)
c.5072del p.Leu1691fs frameshift_variant De novo - - 27479843 Lelieveld SH , et al. (2016)
c.6511C>T p.Gln2171Ter stop_gained De novo - - 27479843 Lelieveld SH , et al. (2016)
c.4566T>A p.Tyr1522Ter stop_gained De novo - - 27479843 Lelieveld SH , et al. (2016)
c.2318C>G p.Ser773Ter stop_gained De novo - - 27479843 Lelieveld SH , et al. (2016)
c.4741C>T p.Gln1581Ter stop_gained De novo - - 27620904 Martnez F , et al. (2016)
delG - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.4395del p.Arg1465SerfsTer16 frameshift_variant Unknown Not paternal - 27824329 Wang T , et al. (2016)
c.5547dup p.Ser1851LysfsTer5 frameshift_variant De novo - Simplex 27848944 Trujillano D , et al. (2016)
c.5570_5573del p.Lys1857SerfsTer17 frameshift_variant De novo - Simplex 27848944 Trujillano D , et al. (2016)
c.1888-2A>G p.? splice_site_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.2938C>T p.Gln980Ter stop_gained De novo - Simplex 28191889 Stessman HA , et al. (2017)
c.5226_5230delAGAAAinsA p.Glu1743AlafsTer9 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.3265C>T p.Arg1089Ter stop_gained De novo - - 28191889 Stessman HA , et al. (2017)
c.2653C>T p.Arg885Ter stop_gained De novo - - 28191889 Stessman HA , et al. (2017)
c.1729C>T p.Gln577Ter stop_gained De novo - Simplex 28263302 C Yuen RK , et al. (2017)
c.1762G>T p.Glu588Ter stop_gained Familial - Simplex 28263302 C Yuen RK , et al. (2017)
c.1762G>T p.Glu588Ter stop_gained Familial - Simplex 28263302 C Yuen RK , et al. (2017)
A>G p.? splice_site_variant Familial - Multiplex 28263302 C Yuen RK , et al. (2017)
G>A p.? splice_site_variant Familial - Multiplex 28263302 C Yuen RK , et al. (2017)
c.G3520G>T;c.3559G>T p.Gly1174Ter;p.Gly1187Ter stop_gained Unknown - Simplex 28263302 C Yuen RK , et al. (2017)
c.5570_5573del p.Lys1857SerfsTer17 frameshift_variant De novo - - 28323383 Zweier M , et al. (2017)
c.4110G>A p.His1339Ilefs77 splice_site_variant De novo - - 28323383 Zweier M , et al. (2017)
c.1595delG p.Gly532fs frameshift_variant De novo - Simplex 28539120 Zahir FR , et al. (2017)
c.6100C>T p.Gln2034Ter stop_gained De novo - - 28554332 Bowling KM , et al. (2017)
c.2242C>T p.Gln748Ter stop_gained De novo - - 28554332 Bowling KM , et al. (2017)
c.5830C>T p.Arg1944Ter stop_gained Familial Paternal - 28708303 Chrot E , et al. (2017)
c.5025+1G>A p.? splice_site_variant De novo - - 28708303 Chrot E , et al. (2017)
G>A p.Val2106Ile missense_variant De novo - - 28714951 Lim ET , et al. (2017)
c.5911G>T p.Glu1971Ter stop_gained De novo - Simplex 28940097 Anazi S , et al. (2017)
delG - frameshift_variant De novo - Simplex 28965761 Turner TN , et al. (2017)
c.6604delT;c.6643delT p.Phe2202fs;p.Phe2215fs frameshift_variant De novo - Simplex 29100083 Hamdan FF , et al. (2017)
c.4110G>A p.(=) splice_site_variant Unknown - - 29286531 Tumien B , et al. (2017)
- - translocation De novo - - 29805044 Halgren C , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

1S

Score Delta: Score remained at 1.1 + S

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.

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."

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).

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).

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
[Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B.2011] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability.2017] [De novo mutations in moderate or severe intellectual disability.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [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] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency.2014] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [The HHID syndrome of hypertrichosis, hyperkeratosis, abnormal corpus callosum, intellectual disability, and minor anomalies is caused by mutations ...2017] [Excess of rare, inherited truncating mutations in autism.2015] [Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA.2016] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability.2016] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome.2012] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.2017] [Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability.2012]
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).

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).

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).

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
[A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome.2012] [Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA.2016] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Excess of rare, inherited truncating mutations in autism.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B.2011] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome.2012] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability.2012] [Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene.2014] [Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency.2014]
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).

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).

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).

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)

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.
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
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
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).
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.
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.
CNVs associated with ARID1B(1 CNVs)
6q25.3 15 Deletion-Duplication 25  /  45
Animal Models associated with ARID1B(8 Models)
ARID1B_1_KO_HT Genetic
ARID1B_1_KO_HT_rhIGF1 RESCUE-Pharmaceutical
ARID1B_1_KO_HT_rmGH RESCUE-Pharmaceutical
ARID1B_2_KO_HM Genetic
ARID1B_3_CKO_HT Genetic
ARID1B_4_CKO_HT Genetic
ARID1B_5_CKO_HT Genetic
ARID1B_6_KO_HT Genetic
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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