VPS16
Chr 20ADVPS16 core subunit of CORVET and HOPS complexes
Also known as: DYT30, hVPS16
The protein localizes to late endosome membranes and mediates vesicle trafficking in the endosome/lysosome pathway. Mutations cause dystonia 30, an autosomal dominant movement disorder. The pathogenic mechanism likely involves disrupted intracellular vesicle transport and lysosomal dysfunction.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The Badonyi & Marsh model scores dominant-negative highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
328 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 11 | 1 | 22 | 0 | 34 |
Likely Pathogenic | 8 | 0 | 2 | 0 | 10 |
VUS | 13 | 186 | 18 | 2 | 219 |
Likely Benign | 0 | 4 | 2 | 14 | 20 |
Benign | 0 | 1 | 11 | 4 | 16 |
Conflicting | — | 4 | |||
| Total | 32 | 192 | 55 | 20 | 303 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
VPS16 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools