ARID1A

Chr 1

AT-rich interaction domain 1A

Also known as: B120, BAF250, BAF250a, BM029, C1orf4, CSS2, ELD, MRD14

NCBI Gene: 8289 ENSG00000117713 UniProt: O14497

The protein functions as a component of SWI/SNF chromatin remodeling complexes that alter DNA-histone contacts in an ATP-dependent manner, with specific roles in neural progenitor-specific (npBAF) and neuron-specific (nBAF) complexes essential for neural stem cell self-renewal and neuronal differentiation. Loss-of-function mutations cause Coffin-Siris syndrome 2, a neurodevelopmental disorder inherited in an autosomal dominant pattern. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SNF/SWI complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SNF/SWI complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.07

Clinical Summary— ARID1A

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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

145 unique Pathogenic / Likely Pathogenic· 766 VUS of 1937 total submissions

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Clinical Trials

11 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ARID1A

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.07LOEUF

pLI 1.000

Z-score 8.55

OE 0.02 (0.01–0.07)

Highly constrained

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

Missense Constraint?

3.66Z-score

OE missense 0.70 (0.66–0.74)

823 obs / 1176.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.07)

0≤0.351.4

Missense OE?0.70 (0.66–0.74)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 2 / 89.0Missense obs/exp: 823 / 1176.0Syn Z: -1.27

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveARID1A-related Coffin-Siris SyndromeLOFAD

This gene — mechanism propensity

0.15100th %ile

GOF

0.1699th %ile

LOF

0.91top 5%

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

LOFprediction above median · 1 literature citation · 74% of P/LP variants are LoF · LOEUF 0.07 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFMutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome1

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

References

1.PMID 22426308 ↗

ClinVar Variant Classifications

1937 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic86

Likely Pathogenic59

VUS766

Likely Benign613

Benign194

Conflicting114

Pathogenic

Likely Pathogenic

766

VUS

613

Likely Benign

194

Benign

114

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	82	3	1	0	86
Likely Pathogenic	25	29	4	1	59
VUS	6	716	26	18	766
Likely Benign	1	154	108	350	613
Benign	0	94	31	69	194
Conflicting	—				114
Total	114	996	170	438	1,832

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap ARID1A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

ARID1A · protein map & ClinVar variants

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

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

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GeneReview available — ARID1A

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Metastatic or Locally Advanced Unresectable Solid Tumors

Study of Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320)

ACTIVE NOT RECRUITING

NCT05396833Phase PHASE1EMD Serono Research & Development Institute, Inc.Started 2022-06-07

TuvusertibLartesertibAvelumab

Uroepithelial Carcinoma

Current Status of Diagnosis and Treatment of Uroepithelial Carcinoma

NOT YET RECRUITING

NCT06663735The First Affiliated Hospital of Xinxiang Medical CollegeStarted 2024-10-30

Solid TumorsER+ Breast CancerTriple Negative Breast Cancer, TNBC

JAB-2485 Activity in Adult Patients With Advanced Solid Tumors

RECRUITING

NCT05490472Phase PHASE1, PHASE2Jacobio Pharmaceuticals Co., Ltd.Started 2022-12-20

JAB-2485 (Aurora A inhibitor)JAB-2485 (Aurora A inhibitor)

Advanced Hepatocellular CarcinomaMetastatic Hepatocellular CarcinomaStage III Hepatocellular Carcinoma AJCC v8

Testing the Addition of an Anti-cancer Drug, Sapanisertib, to the Usual Chemotherapy Treatment (Cabozantinib) in Metastatic Liver Cell Cancer With a Change in Genes for the Protein β-Catenin, The SAPHIRE Trial

RECRUITING

NCT06811116Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2025-11-17

Biospecimen CollectionCabozantinib S-malateImaging Procedure

Solid Tumor MalignanciesClear Cell Endometrial CarcinomaOvarian Cancer

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

RECRUITING

NCT07303387Phase PHASE2Gustave Roussy, Cancer Campus, Grand ParisStarted 2026-03-05

Valemetostat Tosylate

Gynaecological Cancers

ATr Inhibitor in Combination With Olaparib/Durvalumab (MEDI4736) in Gynaecological Cancers With ARId1A Loss or no Loss

ACTIVE NOT RECRUITING

NCT04065269Phase PHASE2Institute of Cancer Research, United KingdomStarted 2019-11-27