SMARCA1

Chr X

SNF2 related chromatin remodeling ATPase 1

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

This gene encodes an ATPase that serves as the catalytic subunit of ISWI chromatin-remodeling complexes, which regulate nucleosome spacing and facilitate DNA replication, transcription, and repair. Mutations cause autosomal dominant neurodevelopmental disorders affecting brain development and neurite outgrowth. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.137), indicating that such variants are likely to be pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.14
Clinical SummarySMARCA1
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 6.01
OE 0.04 (0.020.14)
Highly constrained

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

Missense Constraint
2.44Z-score
OE missense 0.65 (0.580.72)
250 obs / 384.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.020.14)
00.351.4
Missense OE0.65 (0.580.72)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 2 / 46.0Missense obs/exp: 250 / 384.6Syn Z: 0.79
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SMARCA1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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