VPS53: A Key Component of the GARP Complex Involved in Endosomal Trafficking
Comprehensive genomic and functional analysis of VPS53, a gene associated with progressive cerebello-cerebral atrophy and endosomal recycling defects.
Gene Information Card
| Symbol | VPS53 |
|---|---|
| Full Name | VPS53 subunit of GARP complex |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.3 |
| NCBI Gene ID | 55275 ncbi.nlm.nih.gov/gene/55275 |
| Ensembl ID | ENSG00000141380 |
| UniProt ID | Q5VIR6 |
| OMIM ID | 615850 |
| HGNC ID | 25613 |
| Aliases | HCCS1, C17orf44, PPP1R144 |
Description
VPS53 (VPS53 subunit of GARP complex) encodes a protein that is a core component of the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex that facilitates the fusion of endosome-derived vesicles with the trans-Golgi network, playing a critical role in retrograde transport from endosomes to the Golgi apparatus. VPS53 is essential for maintaining Golgi integrity, lysosomal enzyme sorting, and cellular homeostasis. Loss-of-function mutations in VPS53 cause progressive cerebello-cerebral atrophy (PCCA), a severe neurodegenerative disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Progressive cerebello-cerebral atrophy (PCCA) | Biallelic loss-of-function mutations in VPS53 disrupt GARP complex assembly, impairing retrograde endosome-to-Golgi trafficking. This leads to defective lysosomal enzyme sorting, accumulation of autophagic vesicles, and neuronal cell death, particularly in the cerebellum and cerebral cortex. | ClinVar, OMIM (615850), PubMed (Feinstein et al., 2014) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cerebral cortex) | 10.8 | Medium |
| Testis | 8.2 | Low |
| Kidney | 7.1 | Low |
| Liver | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cells |
| SH-SY5Y | 11.4 | Neuroblastoma cell line, relevant for neuronal studies |
| HeLa | 9.8 | Cervical carcinoma cells |
| HepG2 | 6.5 | Hepatocellular carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.208C>T (p.Arg70*) | Nonsense | Rare | Premature stop codon; loss of function; associated with PCCA |
| c.1552C>T (p.Arg518Trp) | Missense | Rare | Impaired GARP complex assembly; reduced retrograde trafficking |
| c.1063-1G>A | Splice site | Rare | Exon skipping; frameshift and protein truncation |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, splice-site) in VPS53 cause progressive cerebello-cerebral atrophy (PCCA) by disrupting GARP complex function and endosomal trafficking.
Gain of Function (GOF)
No gain-of-function mutations reported for VPS53.
Dominant Negative (DN)
No dominant-negative mutations reported; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • intracellular protein transport (GO:0006886) | • retrograde transport (GO:0042147) |
| • Golgi apparatus (GO:0005794) | • TRAPP complex (GO:0030008) |
| • retrograde vesicle-mediated transport (GO:0006890) |
Pathways
• Endosome-to-Golgi retrograde transport (GARP complex)
• Lysosomal enzyme sorting
• Autophagy
Protein Summary
The VPS53 protein (UniProt Q5VIR6) is a 796-amino acid subunit of the GARP complex, which also includes VPS51, VPS52, and VPS54. It localizes to the trans-Golgi network and functions as a tethering factor for endosome-derived vesicles. VPS53 contains a conserved N-terminal domain required for complex assembly and a C-terminal region involved in vesicle recognition. Loss of VPS53 leads to Golgi fragmentation, impaired lysosomal function, and accumulation of autophagic substrates.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS53 Knockout HEK293 Cell Line | EDJ-KQ51441 | Human | 55275 | Details Get a Quote |
| VPS53 Knockout HeLa Cell Line | EDJ-KQ56568 | Human | 55275 | Details Get a Quote |
| VPS53 Knockout A-549 Cell Line | EDJ-KQ65065 | Human | 55275 | Details Get a Quote |
| VPS53 Knockout HCT 116 Cell Line | EDJ-KQ73510 | Human | 55275 | Details Get a Quote |
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