ARID2

Chr 12AD

AT-rich interaction domain 2

Also known as: BAF200, CSS6, SMARCF3, ZIPZAP, p200

NCBI Gene: 196528ENSG00000189079UniProt: Q68CP9

This gene encodes a member of the AT-rich interactive domain (ARID)-containing family of DNA-binding proteins. Members of the ARID family have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation and chromatin structure modification. This protein functions as a subunit of the polybromo- and BRG1-associated factor or PBAF (SWI/SNF-B) chromatin remodeling complex which facilitates ligand-dependent transcriptional activation by nuclear receptors. Mutations in this gene are associated with hepatocellular carcinomas. A pseudogene of this gene is found on chromosome1. [provided by RefSeq, Dec 2016]

Primary Disease Associations & Inheritance

Coffin-Siris syndrome 6MIM #617808
AD
550
ClinVar variants
124
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— ARID2
🧬
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
124 Pathogenic / Likely Pathogenic· 281 VUS of 550 total submissions
💊
Clinical Trials
1 active or recruiting trial — 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 8.00
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.
2.73Z-score
OE missense 0.75 (0.71–0.80)
720 obs / 958.1 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.0.75 (0.71–0.80)
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.1.13
0≤1.21.6
LoF obs/exp: 3 / 80.4Missense obs/exp: 720 / 958.1Syn Z: -1.89

ClinVar Variant Classifications

550 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic86
Likely Pathogenic38
VUS281
Likely Benign117
Benign22
Conflicting6
86
Pathogenic
38
Likely Pathogenic
281
VUS
117
Likely Benign
22
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
46
0
40
0
86
Likely Pathogenic
21
2
15
0
38
VUS
2
263
14
2
281
Likely Benign
0
62
7
48
117
Benign
0
8
9
5
22
Conflicting
—6
Total693358555550

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

View in ClinVar →

Protein Context — Lollipop Plot

ARID2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ARID2-related Coffin-Siris like disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Coffin-Siris syndrome 6

MIM #617808

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — ARID2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic Landscape and Biomarkers of Hepatocellular Carcinoma.
Zucman-Rossi J et al.·Gastroenterology
2015Review
Penetrance, variable expressivity and monogenic neurodevelopmental disorders.
de Masfrand S et al.·Eur J Med Genet
2024
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.
Vasko A et al.·Genes (Basel)
2021
Molecular Characterization of KRAS Wild-type Tumors in Patients with Pancreatic Adenocarcinoma.
Philip PA et al.·Clin Cancer Res
2022Cohort
ARID2-related disorder: further delineation of the clinical phenotype of 27 novel individuals and description of an epigenetic signature.
Houdayer C et al.·Eur J Hum Genet
2025
Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals.
Schmetz A et al.·Hum Genet
2024
Exosome-derived miR-142-5p remodels lymphatic vessels and induces IDO to promote immune privilege in the tumour microenvironment.
Zhou C et al.·Cell Death Differ
2021Functional
Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.
Biankin AV et al.·Nature
2012
PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma.
Yao X et al.·Nat Cell Biol
2023
Integrated molecular characterization of sarcomatoid hepatocellular carcinoma.
Sun RQ et al.·Clin Mol Hepatol
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
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

External Resources

Links to major genomics databases and tools