VPS4A
Vacuolar Protein Sorting 4 Homolog A
Gene Information Card
| Symbol | VPS4A |
|---|---|
| Full Name | Vacuolar Protein Sorting 4 Homolog A |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 27183 ncbi.nlm.nih.gov/gene/27183 |
| Ensembl ID | ENSG00000132612 |
| UniProt ID | Q9UN37 |
| OMIM ID | 609982 |
| HGNC ID | 13488 |
| Aliases | VPS4, SKD1, SKD2, VPS4-1 |
Description
VPS4A encodes an AAA ATPase that catalyzes the disassembly of the endosomal sorting complexes required for transport (ESCRT) machinery, essential for multivesicular body biogenesis, cytokinesis, and viral budding. Mutations in VPS4A cause a neurodevelopmental disorder with microcephaly, spastic paraplegia, and brain malformations.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly, spastic paraplegia, and brain malformations | Loss-of-function mutations impair ESCRT disassembly, leading to defective endosomal trafficking and neuronal dysfunction | ClinVar, OMIM |
| Hereditary spastic paraplegia (rare) | Dominant-negative or hypomorphic variants disrupt membrane fission in neurons | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Testis | 12.8 | Medium |
| Lung | 10.5 | Medium |
| Liver | 8.3 | Low |
| Heart | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | High expression |
| HeLa | 14.2 | Medium expression |
| SH-SY5Y | 12.6 | Medium expression |
| HepG2 | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.850C>T (p.Arg284Trp) | Missense | Rare | Loss of ATPase activity, dominant-negative effect |
| c.1123G>A (p.Glu375Lys) | Missense | Rare | Impaired ESCRT disassembly |
| c.1492C>T (p.Arg498*) | Nonsense | Very rare | Loss of function, protein truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Missense mutations in the ATPase domain (e.g., p.Arg284Trp) that impair hexamer assembly and catalytic activity.
View complete mutation data：
Gene Ontology (GO)
| • ATP hydrolysis activity | • ESCRT III complex disassembly |
| • protein homooligomerization | • endosomal transport |
| • cytokinesis | • viral budding |
Pathways
• ESCRT pathway
• Endosomal sorting
• Multivesicular body biogenesis
Protein Summary
VPS4A is a 437-amino-acid AAA ATPase that forms a hexameric ring. It binds to ESCRT-III filaments via its MIT domain and uses ATP hydrolysis to drive conformational changes that disassemble the ESCRT complex, recycling components for subsequent rounds of membrane fission.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS4A Knockout HEK293 Cell Line | EDJ-KQ51207 | Human | 27183 | Details Get a Quote |
| VPS4A Knockout HeLa Cell Line | EDJ-KQ56026 | Human | 27183 | Details Get a Quote |
| VPS4A Knockout A-549 Cell Line | EDJ-KQ64512 | Human | 27183 | Details Get a Quote |
| VPS4A Knockout HCT 116 Cell Line | EDJ-KQ72970 | Human | 27183 | Details Get a Quote |
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