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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
VPS16
VPS16 core subunit of CORVET and HOPS complexes
Chromosome 20 Β· 20p13
NCBI Gene: 64601Ensembl: ENSG00000215305.11HGNC: HGNC:14584UniProt: Q9H269
92PubMed Papers
21Diseases
0Drugs
21Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
lysosomelate endosomeHOPS complexautophagosome-lysosome fusionDystonianeurodegenerative diseaseCOVID-19genetic disorder
✦AI Summary

VPS16 encodes a core subunit of the CORVET and HOPS endosomal tethering complexes that plays a critical role in vesicle-mediated protein trafficking to lysosomes 1. The protein facilitates autophagosome-lysosome fusion and endosome maturation by regulating SNARE-mediated membrane fusion events 1. VPS16 interacts with vacuolar-H+-ATPase subunit G to control phagosomal acidification, and its disruption can block fusion between lysosomes and phagosomes 1. Pathogenic variants in VPS16 cause DYT-VPS16, a rare monogenic form of dystonia characterized by early-onset (median 12-16.5 years) isolated dystonia that typically begins in cervical, upper limb, or laryngeal regions and progresses to generalization in approximately 50% of cases 23. The phenotypic spectrum has expanded beyond isolated dystonia to include additional features such as myoclonus, choreoathetosis, tremor, and sleep disturbances 42. Deep brain stimulation targeting the globus pallidus internus shows therapeutic efficacy, with approximately 73% of patients demonstrating significant motor improvement, though response varies with disease characteristics and timing of intervention 52. This represents a promising treatment option for this autophagy-related dystonia subtype 6.

Sources cited
1
VPS16 is a core component of endosomal tethering complexes involved in phagosomal acidification and lysosome-phagosome fusion
PMID: 39848245
2
VPS16 variants cause early-onset dystonia with median age at onset of 16.5 years, typically beginning in cervical, upper limb, or laryngeal regions
PMID: 40970427
3
DYT-VPS16 has median age at onset of 12 years, progresses in 95% of cases and generalizes in 50%
PMID: 41200738
4
VPS16-related disease phenotype extends beyond isolated dystonia to include myoclonus, choreoathetosis, and other hyperkinetic movements
PMID: 38291845
5
Deep brain stimulation shows efficacy in VPS16-related dystonia with 73% responder rate and mean 41.6% motor improvement
PMID: 40539388
6
VPS16 is linked to autophagy pathway dysfunction in dystonia pathogenesis
PMID: 37738511
Disease Associationsβ“˜21
DystoniaOpen Targets
0.76Strong
neurodegenerative diseaseOpen Targets
0.53Moderate
COVID-19Open Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
thyroid cancerOpen Targets
0.17Weak
adolescent idiopathic scoliosisOpen Targets
0.16Weak
neutropeniaOpen Targets
0.11Weak
autismOpen Targets
0.11Weak
Coarse facial featuresOpen Targets
0.11Weak
Decreased total neutrophil countOpen Targets
0.11Weak
peripheral neuropathyOpen Targets
0.11Weak
SplenomegalyOpen Targets
0.11Weak
Autosomal dominant focal dystonia, DYT25Open Targets
0.08Suggestive
dystonia 25Open Targets
0.08Suggestive
dystonia 27Open Targets
0.07Suggestive
Primary dystonia, DYT6 typeOpen Targets
0.07Suggestive
torsion dystonia 17Open Targets
0.07Suggestive
Primary dystonia, DYT21 typeOpen Targets
0.07Suggestive
Primary dystonia, DYT13 typeOpen Targets
0.07Suggestive
torsion dystonia 2Open Targets
0.06Suggestive
Dystonia 30UniProt
Pathogenic Variants21
NM_022575.4(VPS16):c.1331+2T>CLikely pathogenic
not provided|VPS16-related disorder|Dystonia 30
β˜…β˜…β˜†β˜†2025
NM_022575.4(VPS16):c.1903C>T (p.Arg635Ter)Pathogenic
not provided|Dystonia 30
β˜…β˜…β˜†β˜†2025β†’ Residue 635
NM_022575.4(VPS16):c.1389C>G (p.Tyr463Ter)Likely pathogenic
not provided|Dystonia 30
β˜…β˜…β˜†β˜†2022β†’ Residue 463
NM_022575.4(VPS16):c.539G>A (p.Trp180Ter)Pathogenic
Dystonia 30
β˜…β˜†β˜†β˜†2026β†’ Residue 180
NM_022575.4(VPS16):c.694C>T (p.Arg232Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 232
NM_022575.4(VPS16):c.1513C>T (p.Arg505Ter)Likely pathogenic
Dystonia 30
β˜…β˜†β˜†β˜†2025β†’ Residue 505
NM_022575.4(VPS16):c.436del (p.Ile146fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 146
NM_022575.4(VPS16):c.1955dup (p.Thr653fs)Pathogenic
Dystonia 30
β˜…β˜†β˜†β˜†2025β†’ Residue 653
NM_022575.4(VPS16):c.1326T>A (p.Tyr442Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 442
NM_022575.4(VPS16):c.1818+2T>GLikely pathogenic
Dystonia 30
β˜…β˜†β˜†β˜†2024
NM_022575.4(VPS16):c.2066dup (p.Gln690fs)Likely pathogenic
Dystonia 30
β˜…β˜†β˜†β˜†2024β†’ Residue 690
NM_022575.4(VPS16):c.2272-18C>ALikely pathogenic
See cases
β˜…β˜†β˜†β˜†2023
NM_022575.4(VPS16):c.1988_1989insG (p.Asn663fs)Likely pathogenic
Dystonia 30
β˜…β˜†β˜†β˜†2021β†’ Residue 663
NM_022575.4(VPS16):c.721_727del (p.Gly241fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 241
NM_022575.4(VPS16):c.1335T>G (p.Tyr445Ter)Pathogenic
VPS16-associated disorder|Dystonia 30
β˜…β˜†β˜†β˜†2020β†’ Residue 445
NM_022575.4(VPS16):c.143-2A>TLikely pathogenic
Dystonia 30
β˜…β˜†β˜†β˜†
NM_022575.4(VPS16):c.1035dup (p.Gly346fs)Likely pathogenic
Dystonia 30
β˜…β˜†β˜†β˜†β†’ Residue 346
NM_022575.4(VPS16):c.244_259delinsGAGAGC (p.Lys82fs)Pathogenic
Dystonia 30
β˜†β˜†β˜†β˜†2021β†’ Residue 82
NM_022575.4(VPS16):c.156C>A (p.Asn52Lys)Pathogenic
Dystonia 30
β˜†β˜†β˜†β˜†2021β†’ Residue 52
NM_022575.4(VPS16):c.1367+2T>CPathogenic
Dystonia 30
β˜†β˜†β˜†β˜†2021
View on ClinVar β†—
Related Genes
UVRAGProtein interaction100%STX7Protein interaction100%STX10Protein interaction100%RAB9AProtein interaction100%STX8Protein interaction100%TECPR2Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
100%
Ovary
94%
Liver
83%
Heart
61%
Brain
54%
Gene Interaction Network
Click a node to explore
VPS16UVRAGSTX7STX10RAB9ASTX8TECPR2
PROTEIN STRUCTURE
Preparing viewer…
PDB4BX9 Β· 2.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.81LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.68 [0.56–0.81]
RankingsWhere VPS16 stands among ~20K protein-coding genes
  • #5,224of 20,598
    Most Researched92
  • #2,144of 5,498
    Most Pathogenic Variants21
  • #6,844of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedVPS16
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetics and Pathogenesis of Dystonia.
PMID: 37738511
Annu Rev Pathol Β· 2024
1.00
2
Genetic Update and Treatment for Dystonia.
PMID: 38612382
Int J Mol Sci Β· 2024
0.90
3
A genome-wide association study identified PRKCB as a causal gene and therapeutic target for Mycobacterium avium complex disease.
PMID: 39848245
Cell Rep Med Β· 2025
0.80
4
Deep Brain Stimulation for VPS16-Related Dystonia: A Multicenter Study.
PMID: 40539388
Ann Neurol Β· 2025
0.70
5
VPS16-Related Dystonia: Expanding the Clinical Spectrum and Therapeutic Insights.
PMID: 40970427
Mov Disord Clin Pract Β· 2026
0.60