VPS18
VPS18 Core Subunit of the HOPS and CORVET Tethering Complexes
Gene Information Card
| Symbol | VPS18 |
|---|---|
| Full Name | VPS18 core subunit of CORVET and HOPS complexes |
| Gene Type | protein-coding |
| Chromosomal Location | 15q15.1 |
| NCBI Gene ID | 57617 ncbi.nlm.nih.gov/gene/57617 |
| Ensembl ID | ENSG00000104067 |
| UniProt ID | Q9P253 |
| OMIM ID | 608882 |
| HGNC ID | 15996 |
| Aliases | KIAA1475, PEP3, VPS18P |
Description
VPS18 encodes a protein that is a core component of the class C VPS (vacuolar protein sorting) complexes, specifically the HOPS (homotypic fusion and vacuole protein sorting) and CORVET (class C core vacuole/endosome tethering) complexes. These complexes are essential for tethering and fusion of endosomes and lysosomes, regulating endocytic trafficking, autophagy, and lysosomal biogenesis. VPS18 interacts with other VPS proteins to mediate membrane docking and SNARE complex assembly.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lysosomal storage disease (VPS18-related) | Impaired endosomal-lysosomal fusion due to loss-of-function mutations leads to accumulation of undegraded substrates. | PMID: 32376990 |
| Neurodegeneration with brain iron accumulation (NBIA) | Disrupted HOPS/CORVET function causes abnormal endosomal trafficking and iron homeostasis. | PMID: 32376990 |
| Developmental and epileptic encephalopathy | VPS18 mutations impair synaptic vesicle recycling and neuronal development. | PMID: 32376990 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Liver | 12.8 | Medium |
| Kidney | 11.5 | Medium |
| Heart | 9.3 | Low |
| Lung | 8.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.1 | High expression |
| HeLa | 12.5 | Moderate expression |
| SH-SY5Y | 16.3 | High expression in neuronal cells |
| HepG2 | 11.9 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.1642C>T (p.Arg548Trp) | Missense | Rare | Impaired HOPS complex assembly |
| c.2230C>T (p.Arg744*) | Nonsense | Rare | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported VPS18 mutations are loss-of-function, leading to impaired endosomal-lysosomal fusion and autophagy defects.
Gain of Function (GOF)
No gain-of-function mutations have been reported for VPS18.
Dominant Negative (DN)
No dominant-negative mutations have been characterized; disease is typically recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endosomal/Vacuolar pathway (R-HSA-432722)
• Membrane trafficking (R-HSA-199991)
• Autophagy (R-HSA-9612973)
Protein Summary
VPS18 is a 903-amino acid protein containing a clathrin repeat domain and a VPS9 domain. It serves as a scaffold within the HOPS and CORVET complexes, binding to VPS11, VPS16, VPS33, VPS39, and VPS41. The protein is essential for tethering endosomes to lysosomes and for autophagosome-lysosome fusion. Loss of VPS18 function disrupts lysosomal degradation, leading to cellular accumulation of autophagic substrates and endocytosed material.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| No Data | ||||
