ARID1A

Chr 1AD

AT-rich interaction domain 1A

NCBI Gene: 8289ENSG00000117713UniProt: O14497

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. Binds DNA non-specifically. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity)

Primary Disease Associations & Inheritance

Coffin-Siris syndrome 2MIM #614607
AD
1931
ClinVar variants
16
Pathogenic / LP
1.00
pLI score· haploinsufficient
12
Active trials
Clinical Summary— ARID1A
⚡
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
16 Pathogenic / Likely Pathogenic· 177 VUS of 1931 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.07LOEUF
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?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.
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?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.0.02 (0.01–0.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.66–0.74)
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.1.08
0≤1.21.6
LoF obs/exp: 2 / 89.0Missense obs/exp: 823 / 1176.0Syn Z: -1.27

ClinVar Variant Classifications

1931 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic8
VUS177
Likely Benign98
Benign24
Conflicting1
8
Pathogenic
8
Likely Pathogenic
177
VUS
98
Likely Benign
24
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
2
0
8
Likely Pathogenic
4
3
1
0
8
VUS
1
162
13
1
177
Likely Benign
0
19
19
60
98
Benign
0
11
1
12
24
Conflicting
—1
Total111953673316

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.

Gene2Phenotype Curations

ARID1A-related Coffin-Siris Syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Coffin-Siris syndrome 2

MIM #614607

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity.
Maxwell MB et al.·Cell
2024
Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression.
Huang KK et al.·Cancer Cell
2023
Genetic Landscape and Biomarkers of Hepatocellular Carcinoma.
Zucman-Rossi J et al.·Gastroenterology
2015Review
Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma.
Montal R et al.·J Hepatol
2020
Non-coding recurrent mutations in chronic lymphocytic leukaemia.
Puente XS et al.·Nature
2015
Whole genomes redefine the mutational landscape of pancreatic cancer.
Waddell N et al.·Nature
2015
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.
Vasko A et al.·Genes (Basel)
2021
Molecular testing for endometrial cancer: An SGO clinical practice statement.
Walsh CS et al.·Gynecol Oncol
2023
ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade.
Shen J et al.·Nat Med
2018
CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis.
Huang YH et al.·Signal Transduct Target Ther
2021
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
Solid TumorARID1A Gene Mutation

Phase II Study of Tazemetostat in Solid Tumors Harboring an ARID1A Mutation

RECRUITING
NCT05023655Phase PHASE2Prisma Health-UpstateStarted 2022-01-06
Tazemetostat
Endometrial CancerARID1A Gene MutationRecurrent Endometrial Carcinoma

Avelumab and M1774 in ARID1A-mutated Endometrial Cancer

RECRUITING
NCT06518564Phase PHASE2Panagiotis Konstantinopoulos, MD, PhDStarted 2024-11-14
AvelumabM1774
Recurrent Endometrial CarcinomaRecurrent Endometrial Clear Cell AdenocarcinomaRecurrent Endometrial Endometrioid Adenocarcinoma

Testing Different Amounts of the Combination of Drugs M1774 and ZEN-3694 for the Treatment of Recurrent Ovarian and Endometrial Cancer

RECRUITING
NCT05950464Phase PHASE1National Cancer Institute (NCI)Started 2023-12-18
BET Bromodomain Inhibitor ZEN-3694Biopsy ProcedureBiospecimen Collection
Gastric CancerGastroEsophageal Cancer

Study of SBRT/Olaparib Followed by Pembrolizumab/Olaparib in Gastric Cancers

ACTIVE NOT RECRUITING
NCT05379972Phase PHASE2University of Colorado, DenverStarted 2023-01-12
PembrolizumabOlaparibStereotactic Body Radiation Therapy
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
Advanced Solid TumorDiffuse Large B Cell LymphomaLymphoma, T-Cell

A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas

RECRUITING
NCT04104776Phase PHASE1, PHASE2Novartis PharmaceuticalsStarted 2019-09-18
TulmimetostatEnzalutamide
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.

NOT YET RECRUITING
NCT07303387Phase PHASE2Gustave Roussy, Cancer Campus, Grand ParisStarted 2026-02-28
Valemetostat Tosylate
Advanced Solid TumorOvarian CancerOvarian Clear Cell Carcinoma

A Phase 1 Clinical Study of NXP800 in Subjects With Advanced Cancers and Expansion in Subjects With Ovarian Cancer

ACTIVE NOT RECRUITING
NCT05226507Phase PHASE1Nuvectis Pharma, Inc.Started 2021-12-31
NXP800
Locally Advanced Bladder Urothelial CarcinomaLocally Advanced Renal Pelvis Urothelial CarcinomaLocally Advanced Ureter Urothelial Carcinoma

ARID1A and/or KDM6A Mutation and CXCL13 Expression

ACTIVE NOT RECRUITING
NCT04953104Phase PHASE2M.D. Anderson Cancer CenterStarted 2021-09-21
Diagnostic Laboratory Biomarker AnalysisNivolumabRelatlimab
Endometrial CarcinomaSerous Carcinoma

Niraparib Monotherapy as Maintain and Recurrent Treatment of Endometrial Serous Carcinoma

RECRUITING
NCT04716686Phase PHASE2Shandong UniversityStarted 2021-06-01
Niraparib
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)

External Resources

Links to major genomics databases and tools