SMARCA5

Chr 4

SNF2 related chromatin remodeling ATPase 5

Also known as: ISWI, SNF2H, WCRF135, hISWI, hSNF2H

SMARCA5 encodes an ATPase that catalyzes chromatin remodeling by sliding nucleosomes along DNA to facilitate transcription, DNA replication, and repair processes. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and various neurological features. The gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 0.074), indicating that even mild reductions in protein function can cause disease.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.07
Clinical SummarySMARCA5
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADModerate

Moderate evidence — consider for supplementary testing

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

Dual constrained — LoF & missense intolerant
LoF Constraint
0.07LOEUF
pLI 1.000
Z-score 7.28
OE 0.02 (0.010.07)
Highly constrained

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

Missense Constraint
5.42Z-score
OE missense 0.35 (0.320.40)
198 obs / 558.2 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.02 (0.010.07)
00.351.4
Missense OE0.35 (0.320.40)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 1 / 63.7Missense obs/exp: 198 / 558.2Syn Z: 1.18
DN
0.3097th %ile
GOF
0.2696th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.07

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

SMARCA5 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →