Human Gene Module / Chromosome 6 / ARID1B

ARID1BAT rich interactive domain 1B (SWI1-like)

Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
17 / 28
Rare Variants / Common Variants
86 / 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
EP, ADHD, EPS, ID, ASD
Relevance to Autism

A de novo deletion resulting in reduced transcript expression was identified within the ARID1B gene in a patient with autism (Nord et al., 2011). In a subsequent study, a de novo translocation disrupting the ARID1B gene was identified in an individual with autism, intellectual disability, agenesis of the corpus callosum, and severe speech impairment (Halgren et al., 2011). Deletions encompassing the ARID1B gene were also identified in patients with autism or autistic traits in this report.

Molecular Function

A component of the SWI/SNF chromatin remodeling complex involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. Mutations in the ARID1B gene are responsible for mental retardation, autosomal dominant 12 (MRD12; OMIM #614562) and some forms of Coffin-Siris syndrome (CSS; OMIM #135900).

Reports related to ARID1B (28 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
Rare Variants   (86)
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_5270​delAGAAAG​insAG p.Glu1756AlafsTer9 frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.4144_4148​delCCCCC​insCCCC 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)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

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

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."

04-01-2017
1S

Initial score established: 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]
CNVs associated with ARID1B(1 CNVs)
6q25.3 13 Deletion-Duplication 21  /  40
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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