• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ARID1B (HGNC:18040) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
AT-rich interaction domain 1B
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
KIAA1235, ELD/OSA1, p250R, BAF250b, DAN15, 6A3-5, SMARCF2
%HI
14.17(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.1(Read more about gnomAD LOEUF score)
Cytoband
6q25.3
Genomic Coordinates
GRCh37/hg19: chr6:157097160-157531913 NCBI Ensembl UCSC
GRCh38/hg38: chr6:156776026-157210779 NCBI Ensembl UCSC
MANE Select Transcript
NM_001374828.1 ENST00000636930.2 (Read more about MANE Select)
Function
Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). Durin... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-31690
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
05/26/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 22426308
    Tsurusaki et al. (2012) performed whole exome sequencing in 23 individuals with Coffin-Siris syndrome (CSS), and identified 5 sequencing variants (1 de novo frameshift; 2 de novo nonsense, 1 missense, and 1 frameshift) and one microdeletion (3.7 Mb) of ARID1B. Mutated transcripts subject to nonsense-mediated mRNA decay were illustrated in two patients with ARID1B variants, suggesting haploinsufficiency of this gene. The authors published additional CSS cases with truncating ARID1B variants (nonsense or frameshift deletion/insertion) in 2014 (PMID: 23815551).
  • PUBMED: 21801163
    Halgren et al (2012) identified a de novo balanced translocation t(1;6)(p31;q25) in an individual with hypotonia, dysmorphic features, agenesis of the corpus callosum, intellectual disability, and autism. This translocation interrupted intron 5 of ARID1B at the chromosome 6 breakpoint; the chromosome 1 breakpoint affected no genes. Further, the authors reported 7 additional patients with intellectual disability and speech impairment who had various sized de novo deletions including the ARID1B gene; in three patients, the deletions were focal and affected only intragenic portion of ARID1B (exons 4-8; exons 2-20; and exons 1-8). Brain MRI was performed in four patients; partial agenesis of corpus callosum (CC) was detected in two of these, one had CC hypoplasia, while one patient had normal CC. Two of the patients had autism spectrum disorder and autistic traits were found in another two. Hypotonia was reported in three patients, and four patients had feeding problems or failure to thrive in infancy.
  • PUBMED: 22405089
    Hoyer et al (2012) reported a 2.5 Mb deletion of 6q25 including ARID1B, 7 nonsense and frameshift variants and a duplication of exons 5 and 6 of ARID1B (all de novo) in patients with intellectual disability, developmental delay, autism, and dysmorphic features. Some individuals have additional clinical findings including agenesis of corpus callosum.
  • PUBMED: 22426309
    Santen et al (2012) identified de novo 2 nonsense variants and 1 frameshift variant in ARID1B in three individuals with Coffin-Siris syndrome (CSS) by exome sequencing. Further, array analysis revealed de novo deletions of ARID1B ((2 focal deletions and 1 larger deletion with additional genes) in 3 patients from 2,000 individuals with intellectual disability.
  • PUBMED: 26376624
    Yu et al (2015) identified de novo copy number variants involving ARID1B associated with both syndromic and non-syndromic short stature. (a 658 kb de novo deletion of 6q25.3 including only ARID1B; a 6.8 Mb de novo deletion of 6q25.1-q25.3, and a 207 kb maternally inherited intragenic duplication involving exons 6-8).
  • PUBMED: 30349098
    van der Sluijs et al (2019) developed a web-based survey (www.arid1bgene.com) based on previously reported features of ARID1B patients. Data were contributed by pediatric neurologists, pediatricians, and in most instances by clinical geneticists. In this study, 79 ARID1B-CSS and 64 ARID1B-ID patients were included. The authors conclude that the ARID1B-related disorders encompass a spectrum of features from nonsyndromic intellectual disability to Coffin–Siris syndrome.
HI Evidence Comments:
ARID1B haploinsufficiency related clinical phenotypes range from classic Coffin-Siris syndrome (CSS) to intellectual disability with or without nonspecific dysmorphic features. CSS is characterized by variable degrees of intellectual disability, speech impairment, coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other findings seen in individuals with ARID1B-related disorder (ARID1B-RD) include feeding difficulties, slow growth, ophthalmologic abnormalities, hearing impairment, seizures, attention deficit/hyperactivity disorder, and autistic features. Almost all individuals diagnosed to date have the disorder as the result of a de novo pathogenic variant. Currently there is no clear genotype-phenotype correlation, suggesting the involvement of other phenotypic modifiers. ARID1B is a member of the SWItch/Sucrose NonFermenting (SWI/SNF) chromatin-remodeling complex, and is highly expressed in the brain and in embryonic stem cells. Approximately 1/2 to 2/3 of individuals with molecularly confirmed CSS have a pathogenic variant in ARID1B. However, heterozygous pathogenic variants in other SWI/SNF subunit genes (ARID1A, DPF2, SMARCC2, SMARCA4, SMARCB1, SMARCE1, and SOX11) also cause CSS. Related articles with de novo loss of function sequence variants of ARID1B in patients with intellectual disability, developmental delay, and autism spectrum disorder: PMID 30559488 PMID 26757139 PMID 25533962 PMID 22495309 PMID 30755392 PMID 26757139

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
At this time there is no evidence that supports the triplosensitivity of ARID1B.

Genomic View

Select assembly: (NC_000006.11) (NC_000006.12)