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: P51531OMIM: 600014

The protein is an ATPase subunit of the SWI/SNF chromatin remodeling complex that regulates gene transcription by altering chromatin structure around target genes. Loss-of-function mutations cause autosomal dominant Nicolaides-Baraitser syndrome and Blepharophimosis-impaired intellectual development syndrome. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the pathogenic mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismADLOEUF 0.202 OMIM phenotypes
Clinical Summary— SMARCA2
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Gene-Disease Validity (ClinGen)
intellectual disability-sparse hair-brachydactyly 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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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
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
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
LoF OE0.12 (0.08–0.20)
0≤0.351.4
Missense OE0.53 (0.49–0.57)
0≤0.61.4
Synonymous OE1.29
0≤1.21.6
LoF obs/exp: 11 / 89.6Missense obs/exp: 476 / 903.5Syn Z: -4.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSMARCA2-related Nicolaides-Baraitser syndromeOTHERAD
DN
0.4488th %ile
GOF
0.4184th %ile
LOF
0.69top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.20
DN1 literature citation

Literature Evidence

DNDominant negative effects of SMARCA2 mutations may contribute to Nicolaides-Baraitser syndrome. We conclude that their features better resemble Coffin-Siris syndrome, rather than Nicolaides-Baraitser syndrome and that these features likely arise from SMARCA2 over-dosage.PMID:27264538

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

0 submitted variants in ClinVar

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.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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