VPS16

Chr 20AD

VPS16 core subunit of CORVET and HOPS complexes

Also known as: DYT30, hVPS16

NCBI Gene: 64601ENSG00000215305UniProt: Q9H269

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 homolog of yeast class C Vps16 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

Primary Disease Associations & Inheritance

Dystonia 30MIM #619291
AD
293
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— VPS16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 212 VUS of 293 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.
0.82LOEUF
pLI 0.000
Z-score 2.62
OE 0.61 (0.46–0.82)
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.
0.82Z-score
OE missense 0.90 (0.83–0.97)
458 obs / 510.3 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.0.61 (0.46–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.83–0.97)
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.0.92
0≤1.21.6
LoF obs/exp: 32 / 52.5Missense obs/exp: 458 / 510.3Syn Z: 0.86

ClinVar Variant Classifications

293 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic10
VUS212
Likely Benign18
Benign16
Conflicting4
33
Pathogenic
10
Likely Pathogenic
212
VUS
18
Likely Benign
16
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
1
26
0
33
Likely Pathogenic
6
0
4
0
10
VUS
8
180
22
2
212
Likely Benign
0
4
1
13
18
Benign
0
1
11
4
16
Conflicting
—4
Total201866419293

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dystonia 30

MIM #619291

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — VPS16
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetics and Pathogenesis of Dystonia.
Thomsen M et al.·Annu Rev Pathol
2024Review
Genetic Update and Treatment for Dystonia.
Koptielow J et al.·Int J Mol Sci
2024Review
Dominant VPS16 Pathogenic Variants: Not Only Isolated Dystonia.
Monfrini E et al.·Mov Disord Clin Pract
2024Case report
Genetic Diversity and Expanded Phenotypes in Dystonia: Insights From Large-Scale Exome Sequencing.
Thomsen M et al.·Ann Clin Transl Neurol
2025
Expanding the Genetic and Phenotypic Spectrum of DYT-VPS16: The Importance of Splice-Site Variants.
Westenberger A et al.·Mov Disord
2026
A genome-wide association study identified PRKCB as a causal gene and therapeutic target for Mycobacterium avium complex disease.
Zheng R et al.·Cell Rep Med
2025
Deep Brain Stimulation for VPS16-Related Dystonia: A Multicenter Study.
Svorenova T et al.·Ann Neurol
2025
Bi-allelic VPS16 variants limit HOPS/CORVET levels and cause a mucopolysaccharidosis-like disease.
Sofou K et al.·EMBO Mol Med
2021
VPS16-Associated Dystonia: A Cohort-Based Clinical, Imaging and Genetic Profile.
Mahale RR et al.·Tremor Other Hyperkinet Mov (N Y)
2025Cohort
Genome sequencing reanalysis increases the diagnostic yield in dystonia.
Fellner A et al.·Parkinsonism Relat Disord
2024
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