SMARCA5

Chr 4

SNF2 related chromatin remodeling ATPase 5

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

NCBI Gene: 8467 ENSG00000153147 UniProt: O60264 OMIM: 603375

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the SWI/SNF family of proteins. 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 protein encoded by this gene is a component of the chromatin remodeling and spacing factor RSF, a facilitator of the transcription of class II genes by RNA polymerase II. The encoded protein is similar in sequence to the Drosophila ISWI chromatin remodeling protein. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADModerateconsider for supplementary testing

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.07

LOEUF· LoF intol.

LOF

Mechanism· predicted