WASHC5

Chr 8ARAD

WASH complex subunit 5

Also known as: KIAA0196, RTSC, RTSC1, SPG8

NCBI Gene: 9897 ENSG00000164961 UniProt: Q12768 OMIM: 610657

The protein strumpellin acts as a component of the WASH core complex that recruits and activates the Arp2/3 complex to induce actin polymerization at endosome surfaces, playing a key role in endosome sorting and cellular trafficking. Mutations cause either autosomal dominant spastic paraplegia 8 characterized by progressive lower extremity spasticity, or autosomal recessive Ritscher-Schinzel syndrome 1 which involves multiple organ systems. This gene is highly intolerant to loss-of-function variants (pLI ~0), indicating it is under strong evolutionary constraint.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a 134 kDa protein named strumpellin that is predicted to have multiple transmembrane domains and a spectrin-repeat-containing domain. This ubiquitously expressed gene has its highest expression in skeletal muscle. The protein is named for Strumpell disease; a form of hereditary spastic paraplegia (HSP). Spastic paraplegias are a diverse group of disorders in which the autosomal dominant forms are characterized by progressive, lower extremity spasticity caused by axonal degeneration in the terminal portions of the longest descending and ascending corticospinal tracts. More than 30 loci (SPG1-33) have been implicated in hereditary spastic paraplegia diseases. [provided by RefSeq, Aug 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ritscher-Schinzel syndrome 1MIM #220210

Spastic paraplegia 8, autosomal dominantMIM #603563

Clinical highlights

Gene-disease validity (ClinGen)

hereditary spastic paraplegia 8 · ADModerateconsider for supplementary testing2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

LOF

Mechanism· G2P

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GeneReview available — WASHC5