VPS41

Chr 7AR

VPS41 subunit of HOPS complex

Also known as: HVPS41, HVSP41, SCAR29, hVps41p

NCBI Gene: 27072ENSG00000006715UniProt: P49754

Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human ortholog of yeast Vps41 protein which is also conserved in Drosophila, tomato, and Arabidopsis. Expression studies in yeast and human indicate that this protein may be involved in the formation and fusion of transport vesicles from the Golgi. Several transcript variants encoding different isoforms have been described for this gene, however, the full-length nature of not all is known. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia, autosomal recessive 29MIM #619389
AR
212
ClinVar variants
31
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— VPS41
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 126 VUS of 212 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.84LOEUF
pLI 0.000
Z-score 2.55
OE 0.64 (0.49–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.48Z-score
OE missense 0.80 (0.73–0.88)
358 obs / 446.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.64 (0.49–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.73–0.88)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 37 / 57.9Missense obs/exp: 358 / 446.1Syn Z: -0.39

ClinVar Variant Classifications

212 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic9
VUS126
Likely Benign10
Benign45
22
Pathogenic
9
Likely Pathogenic
126
VUS
10
Likely Benign
45
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
18
0
22
Likely Pathogenic
1
2
6
0
9
VUS
4
112
10
0
126
Likely Benign
0
3
1
6
10
Benign
0
2
40
3
45
Total7121759212

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia, autosomal recessive 29

MIM #619389

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Atractylenolide I inhibits angiogenesis and reverses sunitinib resistance in clear cell renal cell carcinoma through ATP6V0D2-mediated autophagic degradation of EPAS1/HIF2α.
Li Q et al.·Autophagy
2025
Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition.
Ibarrola-Villava M et al.·Int J Cancer
2015Meta-analysis
Genetic Dystonias: Update on Classification and New Genetic Discoveries.
Keller Sarmiento IJ et al.·Curr Neurol Neurosci Rep
2021Review
An initial HOPS-mediated fusion event is critical for autophagosome transport initiation from the axon terminal.
Wisner SR et al.·Autophagy
2024
Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities.
Steel D et al.·Ann Neurol
2020
MACC1 drives metastasis in colorectal cancer by coordinating YKT6-dependent exosome biogenesis and c-Met cargo selection.
Hou S et al.·Cell Signal
2025
Comprehensive knockout analysis of the RAB family small GTPases reveals an overlapping role of RAB2 and RAB14 in autophagosome maturation.
Haga K et al.·Autophagy
2025
NOX1-Dependent mTORC1 Activation via S100A9 Oxidation in Cancer Stem-like Cells Leads to Colon Cancer Progression.
Ohata H et al.·Cell Rep
2019
Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines.
Roy D et al.·Blood
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools