ARID1B

Chr 6AD

AT-rich interaction domain 1B

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

NCBI Gene: 57492ENSG00000049618UniProt: Q8NFD5

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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

Primary Disease Associations & Inheritance

Coffin-Siris syndrome 1MIM #135900
AD
159
ClinVar variants
26
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— ARID1B
🧬
Gene-Disease Validity (ClinGen)
Coffin-Siris syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 77 VUS of 159 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.02–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.75–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 4 / 90.1Missense obs/exp: 961 / 1214.5Syn Z: -0.12

ClinVar Variant Classifications

159 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic12
VUS77
Likely Benign50
Benign5
Conflicting1
14
Pathogenic
12
Likely Pathogenic
77
VUS
50
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
7
0
14
Likely Pathogenic
5
0
7
0
12
VUS
0
43
34
0
77
Likely Benign
0
13
16
21
50
Benign
0
3
0
2
5
Conflicting
—1
Total12596423159

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.

Gene2Phenotype Curations

ARID1B-related Coffin-Siris Syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Coffin-Siris syndrome 1

MIM #135900

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — ARID1B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell brain organoid screening identifies developmental defects in autism.
Li C et al.·Nature
2023
The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome.
van der Sluijs PJ et al.·Genet Med
2019Cohort
Autism spectrum disorder: neuropathology and animal models.
Varghese M et al.·Acta Neuropathol
2017Review
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.
Vasko A et al.·Genes (Basel)
2021
Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.
Grozeva D et al.·Hum Mutat
2015
De novo mutations in moderate or severe intellectual disability.
Hamdan FF et al.·PLoS Genet
2014
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
Neurobiology of ARID1B haploinsufficiency related to neurodevelopmental and psychiatric disorders.
Moffat JJ et al.·Mol Psychiatry
2022Review
The ARID1B phenotype: what we have learned so far.
Santen GW et al.·Am J Med Genet C Semin Med Genet
2014Review
Microduplications of ARID1A and ARID1B cause a novel clinical and epigenetic distinct BAFopathy.
van der Sluijs PJ et al.·Genet Med
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
Solid Tumor MalignanciesClear Cell Endometrial CarcinomaOvarian Cancer

Efficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.

NOT YET RECRUITING
NCT07303387Phase PHASE2Gustave Roussy, Cancer Campus, Grand ParisStarted 2026-02-28
Valemetostat Tosylate

External Resources

Links to major genomics databases and tools