ARID1B

Chr 6AD

AT-rich interaction domain 1B

Also known as: 6A3-5, BAF250B, BRIGHT, CSS1, DAN15, ELD/OSA1, MRD12, OSA2

NCBI Gene: 57492ENSG00000049618UniProt: Q8NFD5OMIM: 614556

The protein is a component of the SWI/SNF chromatin remodeling complex that functions as an alternative ARID-subunit to regulate gene expression through chromatin modification. Loss-of-function mutations cause Coffin-Siris syndrome 1, an autosomal dominant neurodevelopmental disorder. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the pathogenic mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.101 OMIM phenotype
Clinical Summary— ARID1B
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Gene-Disease Validity (ClinGen)
Coffin-Siris syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
75 unique Pathogenic / Likely Pathogenic· 224 VUS of 500 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — ARID1B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 8.41
OE 0.04 (0.02–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.59Z-score
OE missense 0.79 (0.75–0.83)
961 obs / 1214.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.02–0.10)
0≤0.351.4
Missense OE0.79 (0.75–0.83)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 4 / 90.1Missense obs/exp: 961 / 1214.5Syn Z: -0.12
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveARID1B-related Coffin-Siris SyndromeLOFAD
DN
0.15100th %ile
GOF
0.16100th %ile
LOF
0.91top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 71% of P/LP variants are LoF · LOEUF 0.10

Literature Evidence

LOFHaploinsufficiency of the chromatin remodeling factor ARID1B leads to autism spectrum disorder and intellectual disability.PMID:30149092

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic27
VUS224
Likely Benign141
Benign14
Conflicting2
48
Pathogenic
27
Likely Pathogenic
224
VUS
141
Likely Benign
14
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
34
0
14
0
48
Likely Pathogenic
19
0
8
0
27
VUS
2
130
90
2
224
Likely Benign
0
42
32
67
141
Benign
0
9
0
5
14
Conflicting
—2
Total5518114474456

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ARID1B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients