VPS41

Chr 7AR

VPS41 subunit of HOPS complex

Also known as: HVPS41, HVSP41, SCAR29, hVps41p

This protein functions as a component of the HOPS endosomal tethering complex, mediating vesicle fusion between late endosomes and lysosomes and facilitating autophagosome-lysosome fusion essential for cellular degradation pathways. Biallelic mutations cause spinocerebellar ataxia, autosomal recessive 29 through loss-of-function mechanisms that disrupt vesicle-mediated protein trafficking to lysosomal compartments.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.841 OMIM phenotype
Clinical SummaryVPS41
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
0.84LOEUF
pLI 0.000
Z-score 2.55
OE 0.64 (0.490.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.48Z-score
OE missense 0.80 (0.730.88)
358 obs / 446.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.490.84)
00.351.4
Missense OE0.80 (0.730.88)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 37 / 57.9Missense obs/exp: 358 / 446.1Syn Z: -0.39
DN
0.6455th %ile
GOF
0.5464th %ile
LOF
0.2970th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

VPS41 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC