VPS16: A Key Regulator of Endosomal Trafficking and Lysosomal Function
Comprehensive genomic and clinical overview of VPS16, associated with VPS16-related dystonia and other neurological disorders.
Gene Information Card
| Symbol | VPS16 |
|---|---|
| Full Name | VPS16 core subunit of CORVET and HOPS complexes |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.2 |
| NCBI Gene ID | 64601 ncbi.nlm.nih.gov/gene/64601 |
| Ensembl ID | ENSG00000101220 |
| UniProt ID | Q9H269 |
| OMIM ID | 608205 |
| HGNC ID | 14584 |
| Aliases | hVPS16, VPS16A, VPS16B |
Description
VPS16 encodes a core subunit of the class C VPS (vacuolar protein sorting) complexes CORVET and HOPS, which are essential for endosomal tethering, fusion, and lysosomal biogenesis. The protein mediates membrane trafficking from early to late endosomes and autophagosome-lysosome fusion. Loss-of-function mutations in VPS16 cause autosomal dominant dystonia (DYT-VPS16) and are implicated in neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dystonia 30 (DYT-VPS16) | Loss-of-function mutations impair HOPS complex assembly, disrupting endolysosomal trafficking and autophagy, leading to neuronal dysfunction. | ClinVar, OMIM #619291 |
| Neurodevelopmental disorder with hypotonia and brain abnormalities | Biallelic VPS16 variants cause severe early-onset encephalopathy with impaired lysosomal function. | ClinVar, OMIM #619293 |
| Parkinson disease (susceptibility) | Rare VPS16 variants may contribute to Parkinson's disease risk via lysosomal dysfunction. | ClinVar, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 11.8 | Medium |
| Liver | 9.2 | Medium |
| Kidney | 8.7 | Medium |
| Heart | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.3 | High expression; relevant for neuronal studies |
| HeLa (cervical carcinoma) | 10.1 | Medium expression |
| HEK293 (embryonic kidney) | 9.5 | Medium expression |
| K562 (leukemia) | 6.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1564C>T (p.Arg522Ter) | Nonsense | Rare | Loss of function; truncating mutation associated with DYT-VPS16 |
| c.238G>A (p.Glu80Lys) | Missense | Rare | Loss of function; disrupts CORVET/HOPS binding |
| c.1021_1022del (p.Leu341GlufsTer3) | Frameshift | Rare | Loss of function; premature termination |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein translation |
Mutation functional classification
Loss of Function (LOF)
Dominant and recessive loss-of-function mutations in VPS16 impair endolysosomal trafficking, leading to dystonia and neurodevelopmental disorders.
Gain of Function (GOF)
No gain-of-function mutations reported for VPS16.
Dominant Negative (DN)
Haploinsufficiency is the primary mechanism; dominant-negative effects are not established.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endocytosis (Reactome: R-HSA-432722)
• Membrane Trafficking (Reactome: R-HSA-199991)
• Autophagy (Reactome: R-HSA-9612973)
• Lysosome (KEGG: hsa04142)
Protein Summary
VPS16 is a 840-amino acid protein (UniProt Q9H269) that localizes to endosomal membranes. It forms part of the HOPS and CORVET tethering complexes, which mediate SNARE-dependent fusion of vesicles with endosomes and lysosomes. The protein contains a VPS16 domain and interacts with VPS33, VPS18, and VPS11. Mutations in VPS16 disrupt complex stability, leading to impaired autophagy and lysosomal degradation, particularly in neurons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS16 Knockout HEK293 Cell Line | EDJ-KQ2669 | Human | 64601 | Details Get a Quote |
| VPS16 Knockout A-549 Cell Line | EDJ-KQ23455 | Human | 64601 | Details Get a Quote |
| VPS16 Knockout HCT 116 Cell Line | EDJ-KQ23456 | Human | 64601 | Details Get a Quote |
| VPS16 Knockout HeLa Cell Line | EDJ-KQ23457 | Human | 64601 | Details Get a Quote |
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