VPS39
VPS39 subunit of HOPS complex
Gene Information Card
| Symbol | VPS39 |
|---|---|
| Full Name | VPS39 subunit of HOPS complex |
| Gene Type | protein-coding |
| Chromosomal Location | 15q15.1 |
| NCBI Gene ID | 23339 ncbi.nlm.nih.gov/gene/23339 |
| Ensembl ID | ENSG00000166881 |
| UniProt ID | Q96JC1 |
| OMIM ID | 612188 |
| HGNC ID | 16893 |
| Aliases | hVPS39, VAM6, VPS39L, KIAA0770 |
Description
VPS39 encodes a protein that is a core component of the homotypic fusion and vacuole protein sorting (HOPS) complex. The HOPS complex mediates tethering and fusion of endosomes and lysosomes, playing a critical role in endolysosomal trafficking, autophagy, and lysosome biogenesis. VPS39 interacts with the small GTPase RAB7 and is essential for late endosome-lysosome fusion. Mutations in VPS39 are associated with a multisystem disorder characterized by neurological impairment, developmental delay, and dysmorphic features.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| VPS39-related disorder (neurodevelopmental disease with lysosomal dysfunction) | Loss-of-function mutations impair HOPS complex assembly, disrupting endolysosomal fusion and leading to accumulation of autophagic and endocytic cargo. | PMID: 28554332, ClinVar |
| VPS39-associated microcephaly and intellectual disability | Biallelic missense variants reduce VPS39 stability and HOPS complex activity, causing neuronal dysfunction. | PMID: 28554332 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 10.1 | Medium |
| Heart | 7.6 | Low |
| Lung | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 11.8 | Moderate expression |
| SH-SY5Y | 9.5 | Moderate expression |
| HepG2 | 8.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1552C>T (p.Arg518*) | Nonsense | Rare | Loss of function; premature termination |
| c.1124G>A (p.Arg375Gln) | Missense | Rare | Impaired HOPS complex binding |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of translation initiation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants lead to truncated or absent VPS39 protein, disrupting HOPS complex assembly and endolysosomal fusion.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Missense variants may act in a dominant-negative manner by forming nonfunctional HOPS complexes, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endolysosomal trafficking (HOPS complex)
• Autophagy (lysosomal fusion)
• RAB7 signaling
Protein Summary
VPS39 is a 100 kDa protein that localizes to late endosomes and lysosomes. It contains a longin domain and a VPS39-specific domain that mediate interactions with VPS41, VPS11, and RAB7. As part of the HOPS complex, VPS39 facilitates tethering of opposing membranes and SNARE complex assembly, enabling fusion of late endosomes with lysosomes. Loss of VPS39 function leads to enlarged vacuoles, impaired autophagic flux, and accumulation of undigested material.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS39 Knockout HEK293 Cell Line | EDJ-KQ7301 | Human | 23339 | Details Get a Quote |
| VPS39 Knockout A-549 Cell Line | EDJ-KQ33681 | Human | 23339 | Details Get a Quote |
| VPS39 Knockout HCT 116 Cell Line | EDJ-KQ33683 | Human | 23339 | Details Get a Quote |
| VPS39 Knockout HeLa Cell Line | EDJ-KQ33684 | Human | 23339 | Details Get a Quote |
