VPS54: A Key Component of the GARP Complex Involved in Vesicular Trafficking
Comprehensive genomic and proteomic overview of VPS54, its role in cellular transport, associated diseases, and expression profiles.
Gene Information Card
| Symbol | VPS54 |
|---|---|
| Full Name | VPS54 subunit of GARP complex |
| Gene Type | protein-coding |
| Chromosomal Location | 2p14 |
| NCBI Gene ID | 51542 ncbi.nlm.nih.gov/gene/51542 |
| Ensembl ID | ENSG00000115970 |
| UniProt ID | Q9NWH7 |
| OMIM ID | 615544 |
| HGNC ID | HGNC:1345 |
| Aliases | HCC8, VPS54L, PPP1R166 |
Description
VPS54 encodes a component of the Golgi-associated retrograde protein (GARP) complex, which is involved in tethering and fusion of endosome-derived vesicles to the trans-Golgi network. The protein is essential for proper lysosomal enzyme sorting and maintenance of Golgi integrity. Mutations in VPS54 are associated with progressive motor neuron degeneration and other neurodegenerative phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) | Impaired retrograde trafficking due to VPS54 loss-of-function leads to lysosomal dysfunction and neuronal death. | ClinVar, OMIM |
| Amyotrophic lateral sclerosis (ALS) | Reduced VPS54 expression disrupts GARP complex assembly, affecting vesicle transport and contributing to motor neuron degeneration. | NCBI, PubMed |
| Neurodegeneration | Defective GARP complex impairs endosome-to-Golgi transport, causing accumulation of autophagic substrates and cellular stress. | UniProt, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Liver | 6.1 | Low |
| Heart | 5.4 | Low |
| Kidney | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 10.8 | Moderate expression |
| SH-SY5Y | 9.1 | Moderate expression |
| HepG2 | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Premature stop, loss of function |
| c.789_790del (p.Glu264fs) | Frameshift | <0.01% | Frameshift, loss of function |
| c.1567G>A (p.Gly523Arg) | Missense | <0.01% | Impaired GARP complex assembly |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent VPS54 protein, disrupting GARP complex function and retrograde transport.
Gain of Function (GOF)
No gain-of-function mutations reported for VPS54.
Dominant Negative (DN)
Missense mutations such as p.Gly523Arg may exert dominant-negative effects by interfering with GARP complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • protein transport | • Golgi to endosome transport |
| • retrograde transport | • endosome to Golgi |
| • GARP complex | • tethering complex |
Pathways
• Endosome-to-Golgi retrograde transport
• GARP complex pathway
• Lysosomal enzyme sorting
Protein Summary
VPS54 is a 977-amino-acid protein that forms part of the GARP tethering complex, which also includes VPS51, VPS52, and VPS53. It localizes to the trans-Golgi network and mediates the docking of endosome-derived vesicles. The protein contains a coiled-coil domain essential for complex assembly and interaction with SNARE proteins. Loss of VPS54 function leads to defective lysosomal biogenesis and neurodegeneration.
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