ARID1A
Chr 1ADAT-rich interaction domain 1A
Also known as: B120, BAF250, BAF250a, BM029, C1orf4, CSS2, ELD, MRD14
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.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 8 | 0 | 0 | 0 | 8 |
Likely Pathogenic | 0 | 2 | 1 | 0 | 3 |
VUS | 0 | 87 | 1 | 3 | 91 |
Likely Benign | 0 | 15 | 6 | 42 | 63 |
Benign | 0 | 9 | 0 | 8 | 17 |
Conflicting | — | 8 | |||
| Total | 8 | 113 | 8 | 53 | 190 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ARID1A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Efficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.
RECRUITINGARID1A and/or KDM6A Mutation and CXCL13 Expression
ACTIVE NOT RECRUITINGA Phase 1 Clinical Study of NXP800 in Subjects With Advanced Cancers and Expansion in Subjects With Ovarian Cancer
ACTIVE NOT RECRUITINGTesting Different Amounts of the Combination of Drugs M1774 and ZEN-3694 for the Treatment of Recurrent Ovarian and Endometrial Cancer
RECRUITINGAvelumab and M1774 in ARID1A-mutated Endometrial Cancer
RECRUITINGNiraparib Monotherapy as Maintain and Recurrent Treatment of Endometrial Serous Carcinoma
RECRUITINGATr Inhibitor in Combination With Olaparib/Durvalumab (MEDI4736) in Gynaecological Cancers With ARId1A Loss or no Loss
ACTIVE NOT RECRUITINGA Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas
RECRUITINGJAB-2485 Activity in Adult Patients With Advanced Solid Tumors
RECRUITINGTesting 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
RECRUITINGStudy of Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320)
ACTIVE NOT RECRUITINGStudy of SBRT/Olaparib Followed by Pembrolizumab/Olaparib in Gastric Cancers
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools