VPS41: A Key Regulator of Vesicle Trafficking and Lysosomal Function
Comprehensive genomic and functional analysis of VPS41, a core component of the HOPS complex involved in endolysosomal sorting and autophagy.
Gene Information Card
| Symbol | VPS41 |
|---|---|
| Full Name | VPS41 subunit of HOPS complex |
| Gene Type | protein-coding |
| Chromosomal Location | 7p14.1 |
| NCBI Gene ID | 27072 ncbi.nlm.nih.gov/gene/27072 |
| Ensembl ID | ENSG00000106344 |
| UniProt ID | Q9H9H4 |
| OMIM ID | 605485 |
| HGNC ID | 16879 |
| Aliases | hVPS41, VPS41P, HSPC300, MGC13170 |
Description
VPS41 encodes a protein that is a core subunit of the homotypic fusion and protein sorting (HOPS) complex, which is essential for tethering and fusion of vesicles to the lysosome. It also participates in autophagy, endolysosomal trafficking, and the biogenesis of lysosome-related organelles. Mutations in VPS41 are associated with neurodevelopmental disorders and lysosomal storage phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly, seizures, and brain atrophy | Loss of VPS41 function disrupts HOPS complex assembly, impairing lysosomal fusion and autophagy, leading to neuronal cell death. | ClinVar, OMIM |
| Lysosomal storage disease-like phenotype | Defective endolysosomal trafficking due to VPS41 deficiency causes accumulation of autophagic substrates and lysosomal dysfunction. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 10.1 | Medium |
| Heart | 7.2 | Low |
| Testis | 15.6 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.8 | Medium expression |
| SH-SY5Y | 13.0 | High expression |
| HepG2 | 9.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Ter) | Nonsense | Rare | Loss of function; truncated protein |
| c.1567G>A (p.Glu523Lys) | Missense | Rare | Impaired HOPS complex binding |
| c.2044_2045del (p.Leu682ValfsTer3) | Frameshift | Rare | Loss of function; premature termination |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent VPS41 protein, disrupting HOPS complex function and lysosomal fusion.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations (e.g., p.Glu523Lys) may act as dominant-negative by disrupting HOPS complex assembly.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endocytosis (Reactome: R-HSA-432722)
• Autophagy (Reactome: R-HSA-9612973)
• Lysosome biogenesis (Reactome: R-HSA-432722)
Protein Summary
VPS41 is a 100 kDa protein that forms part of the HOPS tethering complex, which mediates the fusion of late endosomes and autophagosomes with lysosomes. It contains a clathrin heavy chain repeat domain and interacts with other HOPS subunits (VPS11, VPS16, VPS18, VPS33, VPS39). The protein is ubiquitously expressed, with highest levels in testis and brain. Loss of VPS41 function leads to impaired lysosomal degradation and accumulation of autophagic vesicles, contributing to neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS41 Knockout HEK293 Cell Line | EDJ-KQ8668 | Human | 27072 | Details Get a Quote |
| VPS41 Knockout HCT 116 Cell Line | EDJ-KQ34844 | Human | 27072 | Details Get a Quote |
| VPS41 Knockout HeLa Cell Line | EDJ-KQ34845 | Human | 27072 | Details Get a Quote |
| VPS41 Knockout A-549 Cell Line | EDJ-KQ64480 | Human | 27072 | Details Get a Quote |
