WASHC5

Chr 8ARAD

WASH complex subunit 5

Also known as: KIAA0196, RTSC, RTSC1, SPG8

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.742 OMIM phenotypes
Clinical SummaryWASHC5
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Gene-Disease Validity (ClinGen)
hereditary spastic paraplegia 8 · ADModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.000
Z-score 3.29
OE 0.57 (0.440.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.30Z-score
OE missense 0.85 (0.790.92)
527 obs / 617.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.440.74)
00.351.4
Missense OE0.85 (0.790.92)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 39 / 68.3Missense obs/exp: 527 / 617.6Syn Z: -0.46
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongWASHC5-related intellectual disability, congenital cardiac malformation, and Dandy-Walker malformationLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.6833th %ile
LOF
0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

WASHC5 · 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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