VPS29: A Core Component of the Retromer Complex in Endosomal Trafficking
Comprehensive genomic and proteomic analysis of VPS29, a vacuolar protein sorting-associated factor involved in retromer-mediated cargo recycling.
Gene Information Card
| Symbol | VPS29 |
|---|---|
| Full Name | VPS29 retromer complex component |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.11 |
| NCBI Gene ID | 51699 ncbi.nlm.nih.gov/gene/51699 |
| Ensembl ID | ENSG00000111237 |
| UniProt ID | Q9UBQ0 |
| OMIM ID | 606933 |
| HGNC ID | 14341 |
| Aliases | DC15, DC7, PEP11, VPS29P, CGI-56 |
Description
VPS29 is a core component of the retromer complex, which is essential for endosomal sorting and recycling of transmembrane receptors. It forms a subcomplex with VPS26 and VPS35 that recognizes cargo proteins and recruits additional factors for vesicle formation. VPS29 has also been implicated in the regulation of Wnt signaling and lysosomal enzyme trafficking. Mutations and dysregulation of VPS29 are associated with neurodegenerative disorders, including Parkinson disease and Alzheimer disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson disease | Impaired retromer function leads to defective trafficking of autophagy-related proteins and accumulation of alpha-synuclein. | PMID: 24607389 |
| Alzheimer disease | Reduced retromer activity disrupts amyloid precursor protein (APP) recycling, increasing amyloid-beta production. | PMID: 18614017 |
| Retinitis pigmentosa | VPS29 mutations may disrupt photoreceptor outer segment protein trafficking. | PMID: 26063662 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 10.1 | Medium |
| Heart | 7.2 | Low |
| Lung | 9.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| SH-SY5Y | 11.4 | Neuronal cell line |
| HeLa | 13.7 | Cervical cancer cell line |
| HepG2 | 9.5 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.197G>A (p.Arg66His) | Missense | Rare | Reduced retromer complex stability |
| c.334C>T (p.Arg112Cys) | Missense | Rare | Impaired cargo recognition |
| c.458A>G (p.Asn153Ser) | Missense | Rare | Altered protein interaction |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg66His) reduce retromer complex assembly and endosomal trafficking efficiency.
Gain of Function (GOF)
No known gain-of-function mutations reported.
Dominant Negative (DN)
Heterozygous mutations may disrupt retromer function in a dominant-negative manner, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • intracellular protein transport (GO:0006886) | • endosomal transport (GO:0016197) |
| • retromer complex (GO:0030904) | • intracellular membrane-bounded organelle (GO:0043231) |
| • endosome (GO:0005768) |
Pathways
• Retromer-mediated cargo recycling (Reactome: R-HSA-917937)
• Wnt signaling pathway (KEGG: hsa04310)
• Endosomal sorting complex required for transport (ESCRT) (Reactome: R-HSA-917729)
Protein Summary
VPS29 is a 182-amino acid protein (20.5 kDa) that adopts a metallophosphoesterase fold but lacks catalytic activity. It serves as a structural scaffold within the retromer complex, bridging VPS26 and VPS35. The protein is ubiquitously expressed and localizes to endosomal membranes. Post-translational modifications include phosphorylation at Ser14, which may regulate complex assembly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS29 Knockout HEK293 Cell Line | EDJ-KQ51342 | Human | 51699 | Details Get a Quote |
| VPS29 Knockout HeLa Cell Line | EDJ-KQ56348 | Human | 51699 | Details Get a Quote |
| VPS29 Knockout A-549 Cell Line | EDJ-KQ64837 | Human | 51699 | Details Get a Quote |
| VPS29 Knockout HCT 116 Cell Line | EDJ-KQ73282 | Human | 51699 | Details Get a Quote |
