SMARCA2

Chr 9AD

SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2

Also known as: BAF190, BIS, BRM, NCBRS, SAMRCA2, SNF2, SNF2L2, SNF2LA

NCBI Gene: 6595ENSG00000080503UniProt: P51531

The protein encoded by this gene is a member of the SWI/SNF family of proteins and is highly similar to the brahma protein of Drosophila. Members of this family 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, which contains a trinucleotide repeat (CAG) length polymorphism. [provided by RefSeq, Jan 2014]

Primary Disease Associations & Inheritance

Blepharophimosis-impaired intellectual development syndromeMIM #619293
AD
Nicolaides-Baraitser syndromeMIM #601358
AD
UniProtSchizophrenia
1738
ClinVar variants
41
Pathogenic / LP
1.00
pLI score· haploinsufficient
4
Active trials
Clinical Summary— SMARCA2
⚡
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
41 Pathogenic / Likely Pathogenic· 233 VUS of 1738 total submissions
💊
Clinical Trials
4 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.
0.20LOEUF
pLI 1.000
Z-score 7.69
OE 0.12 (0.08–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
5.05Z-score
OE missense 0.53 (0.49–0.57)
476 obs / 903.5 exp
Constrained

Extremely missense-constrained (top ~0.01%)

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.0.12 (0.08–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.49–0.57)
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.1.29
0≤1.21.6
LoF obs/exp: 11 / 89.6Missense obs/exp: 476 / 903.5Syn Z: -4.19

ClinVar Variant Classifications

1738 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic21
VUS233
Likely Benign166
Benign10
Conflicting4
20
Pathogenic
21
Likely Pathogenic
233
VUS
166
Likely Benign
10
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
8
12
0
20
Likely Pathogenic
0
16
5
0
21
VUS
5
190
36
2
233
Likely Benign
2
16
66
82
166
Benign
0
6
2
2
10
Conflicting
—4
Total723612186454

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

View in ClinVar →

Protein Context — Lollipop Plot

SMARCA2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SMARCA2-related Nicolaides-Baraitser syndrome

definitive
ADUndeterminedAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersSkin
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Blepharophimosis-impaired intellectual development syndrome

MIM #619293

Molecular basis of disorder known

Autosomal dominant

Nicolaides-Baraitser syndrome

MIM #601358

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SMARCA4: Current status and future perspectives in non-small-cell lung cancer.
Tian Y et al.·Cancer Lett
2023Review
PRT3789 Is a First-in-Human SMARCA2-Selective Degrader That Induces Synthetic Lethality in SMARCA4-Mutated Cancers.
Hulse M et al.·Cancer Res
2026
SWI/SNF-deficient thoraco-pulmonary neoplasms.
Sesboue C et al.·Semin Diagn Pathol
2021Review
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
SMARCA4: Promises and challenges in the treatment of cancers.
Ye W et al.·Cancer Lett
2025Review
SMARCA4 and SMARCA2 co-deficiency: An uncommon molecular signature defining a subset of rare, aggressive and undifferentiated malignancies associated with defective chromatin remodeling.
Field NR et al.·Cancer Lett
2024Review
BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or menin inhibitor.
Fiskus W et al.·Blood
2024
Expanding the clinicopathologic spectrum and genomic landscape of tumors with SMARCA2/4::CREM fusions.
Cyrta J et al.·J Pathol
2024
Genotype and phenotype correlation in epilepsy patients with SMARCA2 variants.
Yang Y et al.·Seizure
2025Cohort
Synthetic lethality: targeting the SMARCA2 bromodomain for degradation in SMARCA4-deficient tumors - a review of patent literature from 2019-June 2023.
Lee ECY et al.·Expert Opin Ther Pat
2024Review
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
Metastatic Solid TumorAdvanced Solid TumorNon-small Cell Lung Cancer

A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors

RECRUITING
NCT06561685Phase PHASE1Eli Lilly and CompanyStarted 2024-09-19
LY4050784PembrolizumabCisplatin
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
Esophageal Squamous Cell CarcinomaGastric AdenocarcinomaGastric Squamous Cell Carcinoma

First-in-Human Study of PLX-61639 in Locally Advanced or Metastatic Solid Tumors

RECRUITING
NCT07284186Phase PHASE1Plexium, Inc.Started 2025-12-01
PLX-61639
Mantle Cell Lymphoma Refractory

Genetically Risk-Stratified Venetoclax, Ibrutinib, Rituximab (± Navitoclax) in Relapsed/Refractory Mantle Cell Lymphoma

ACTIVE NOT RECRUITING
NCT05864742Phase PHASE2Peter MacCallum Cancer Centre, AustraliaStarted 2023-09-07
IbrutinibVenetoclaxNavitoclax

External Resources

Links to major genomics databases and tools