VPS52: GARP Complex Subunit and Vesicle Trafficking Regulator
A key component of the Golgi-associated retrograde protein complex involved in endosome-to-Golgi transport and linked to neurological and developmental disorders.
Gene Information Card
| Symbol | VPS52 |
|---|---|
| Full Name | VPS52 subunit of GARP complex |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.2 |
| NCBI Gene ID | 6293 ncbi.nlm.nih.gov/gene/6293 |
| Ensembl ID | ENSG00000112306 |
| UniProt ID | Q8N1B4 |
| OMIM ID | 607849 |
| HGNC ID | 12697 |
| Aliases | SAC2, ARE1, VPS52 (yeast homolog) |
Description
VPS52 encodes a subunit of the Golgi-associated retrograde protein (GARP) complex, which is essential for tethering endosome-derived vesicles to the trans-Golgi network. The GARP complex facilitates retrograde transport of proteins from endosomes to the Golgi apparatus. VPS52 interacts with other GARP subunits (VPS51, VPS53, VPS54) and is critical for maintaining Golgi integrity and lysosome biogenesis. Loss-of-function mutations in VPS52 are associated with autosomal recessive neurodevelopmental disorders, including cerebellar atrophy and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with cerebellar atrophy and intellectual disability | Biallelic loss-of-function mutations in VPS52 disrupt GARP complex assembly, impairing retrograde vesicle trafficking and leading to neuronal dysfunction and cerebellar degeneration. | ClinVar, OMIM (607849) |
| Pontocerebellar hypoplasia (suspected) | Impaired endosome-to-Golgi transport due to VPS52 deficiency may affect neuronal survival and synaptic function. | OMIM (607849) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 10.2 | Medium |
| Testis | 8.9 | Low |
| Heart | 7.1 | Low |
| Liver | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | Neuronal model |
| HeLa (cervical carcinoma) | 12.8 | Epithelial model |
| HEK293 (embryonic kidney) | 11.4 | Common expression system |
| K562 (leukemia) | 9.7 | Hematopoietic model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense (start loss) | Rare | Loss of translation initiation; predicted loss of function |
| c.226C>T (p.Arg76*) | Nonsense | Rare | Premature stop; nonsense-mediated decay |
| c.1048_1049del (p.Leu350Glufs*2) | Frameshift deletion | Rare | Frameshift leading to truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, start loss) are the primary mechanism in VPS52-associated neurodevelopmental disorders.
Gain of Function (GOF)
No gain-of-function mutations reported for VPS52.
Dominant Negative (DN)
No dominant-negative mutations reported for VPS52.
View complete mutation data：
Gene Ontology (GO)
Pathways
• GARP complex-mediated retrograde transport (Reactome: R-HSA-6811434)
• Endosome-to-Golgi transport (KEGG: hsa04142)
Protein Summary
VPS52 is a 723-amino-acid protein (UniProt Q8N1B4) that localizes to the trans-Golgi network as part of the GARP complex. It contains a coiled-coil domain that mediates interactions with other GARP subunits and vesicle-associated SNAREs. The protein is essential for tethering endosome-derived vesicles to the Golgi, facilitating the recycling of membrane proteins such as mannose-6-phosphate receptors. Loss of VPS52 function leads to Golgi fragmentation, impaired lysosomal enzyme sorting, and neuronal cell death.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS52 Knockout HEK293 Cell Line | EDJ-KQ50607 | Human | 6293 | Details Get a Quote |
| VPS52 Knockout HeLa Cell Line | EDJ-KQ54387 | Human | 6293 | Details Get a Quote |
| VPS52 Knockout A-549 Cell Line | EDJ-KQ62880 | Human | 6293 | Details Get a Quote |
| VPS52 Knockout HCT 116 Cell Line | EDJ-KQ71346 | Human | 6293 | Details Get a Quote |
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