VPS11: Core Component of the HOPS and CORVET Tethering Complexes
Essential for Endolysosomal Trafficking and Vesicle Fusion
Gene Information Card
| Symbol | VPS11 |
|---|---|
| Full Name | VPS11 core subunit of CORVET and HOPS complexes |
| Gene Type | Protein coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 55823 ncbi.nlm.nih.gov/gene/55823 |
| Ensembl ID | ENSG00000160606 |
| UniProt ID | Q9H270 |
| OMIM ID | 608549 |
| HGNC ID | 14583 |
| Aliases | END1, PEP5, RNF108, VPS11P |
Description
VPS11 encodes a core component of the class C VPS/HOPS and CORVET tethering complexes, which mediate tethering and fusion of endocytic vesicles with lysosomes and vacuoles. The protein contains a RING-H2 zinc finger domain and is essential for endolysosomal trafficking, autophagy, and lysosome biogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leukoencephalopathy with calcifications and cysts (LCC) | Loss-of-function mutations impair HOPS/CORVET complex assembly, disrupting endolysosomal trafficking and leading to white matter degeneration and cyst formation. | ClinVar, OMIM |
| Neurodegeneration with brain iron accumulation (NBIA) | Defective VPS11 causes impaired lysosomal function and iron homeostasis, contributing to iron deposition in the basal ganglia. | ClinVar, OMIM |
| Lysosomal storage disorder | Dysfunctional VPS11 leads to accumulation of undegraded substrates in lysosomes, similar to other HOPS complex mutations. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 7.1 | Low |
| Lung | 6.9 | Low |
| Heart | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Moderate expression |
| HeLa | 10.8 | Moderate expression |
| SH-SY5Y | 18.6 | Higher in neuronal cells |
| HepG2 | 9.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.259C>T (p.Arg87Trp) | Missense | Rare | Loss of function; disrupts HOPS complex assembly |
| c.847C>T (p.Arg283*) | Nonsense | Rare | Premature truncation; loss of function |
| c.1285G>A (p.Glu429Lys) | Missense | Rare | Impaired binding to VPS18; dominant negative effect |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that disrupt protein folding or complex assembly, leading to impaired endolysosomal trafficking.
Gain of Function (GOF)
Not reported for VPS11.
Dominant Negative (DN)
Missense mutations (e.g., p.Glu429Lys) that retain partial function but disrupt HOPS/CORVET complex integrity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endocytosis (KEGG hsa04144)
• Lysosome (KEGG hsa04142)
• Autophagy - animal (KEGG hsa04140)
• HOPS/CORVET complex mediated vesicle tethering (Reactome R-HSA-917729)
Protein Summary
VPS11 is a 940-amino acid protein containing a N-terminal RING-H2 zinc finger domain and a C-terminal VPS11-specific domain. It forms a stable complex with VPS16, VPS18, and VPS33 (class C VPS/HOPS) and with VPS3, VPS8, and VPS33 (CORVET). The protein localizes to late endosomes and lysosomes, where it facilitates SNARE-mediated membrane fusion. Mutations in VPS11 cause autosomal recessive leukoencephalopathy with calcifications and cysts (LCC) and are associated with neurodegeneration with brain iron accumulation (NBIA).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS11 Knockout HEK293 Cell Line | EDJ-KQ16104 | Human | 55823 | Details Get a Quote |
| VPS11 Knockout HCT 116 Cell Line | EDJ-KQ46031 | Human | 55823 | Details Get a Quote |
| VPS11 Knockout A-549 Cell Line | EDJ-KQ47257 | Human | 55823 | Details Get a Quote |
| VPS11 Knockout HeLa Cell Line | EDJ-KQ47259 | Human | 55823 | Details Get a Quote |
