SMARCA1

Chr X

SNF2 related chromatin remodeling ATPase 1

Also known as: ISWI, NURF140, SNF2L, SNF2L1, SNF2LB, SNF2LT, SWI, SWI2

NCBI Gene: 6594ENSG00000102038UniProt: P28370

This gene encodes a member of the SWI/SNF family of proteins. The encoded protein is an ATPase which is expressed in diverse tissues and contributes to the chromatin remodeling complex that is involved in transcription. The protein may also play a role in DNA damage, growth inhibition and apoptosis of cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

0
Active trials
114
Pathogenic / LP
277
ClinVar variants
13
Pubs (1 yr)
2.4
Missense Z
0.14
LOEUF· LoF intolerant
Clinical Summary— SMARCA1
🧬
Gene-Disease Validity (ClinGen)
X-linked intellectual disability · XLLimited

Limited evidence — not for standalone diagnostic reporting

⚡
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
114 Pathogenic / Likely Pathogenic· 144 VUS of 277 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 6.01
OE 0.04 (0.02–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.44Z-score
OE missense 0.65 (0.58–0.72)
250 obs / 384.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.02–0.14)
0≤0.351.4
Missense OE0.65 (0.58–0.72)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 2 / 46.0Missense obs/exp: 250 / 384.6Syn Z: 0.79
LOF
DN
0.4289th %ile
GOF
0.3392th %ile
LOF
0.68top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.14

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

277 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic100
Likely Pathogenic14
VUS144
Likely Benign13
Benign4
Conflicting2
100
Pathogenic
14
Likely Pathogenic
144
VUS
13
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
100
0
100
Likely Pathogenic
2
0
12
0
14
VUS
3
117
22
2
144
Likely Benign
0
4
2
7
13
Benign
0
3
0
1
4
Conflicting
—2
Total512413610277

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

View in ClinVar →

SMARCA1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
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