VPS4A (Vacuolar Protein Sorting 4 Homolog A) encodes an AAA+ ATPase involved in endosomal sorting, multivesicular body formation, and autophagy. It plays critical roles in membrane protein trafficking and has been implicated in neurodegenerative diseases.
VPS4A (Vacuolar Protein Sorting 4 Homolog A) encodes a key AAA ATPase involved in endosomal sorting, multivesicular body formation, and autophagy. It plays a critical role in recycling membrane proteins and has been implicated in neurodegenerative diseases through its function in lysosomal trafficking.
| Attribute |
Value |
| Symbol |
VPS4A |
| Full Name |
Vacuolar Protein Sorting 4 Homolog A |
| Chromosomal Location |
16q22.1 |
| NCBI Gene ID |
27183 |
| OMIM |
609434 |
| Ensembl ID |
ENSG00000167842 |
| UniProt ID |
Q9Y5X0 |
| Associated Diseases |
Charcot-Marie-Tooth Disease, ALS, FTD, Breast Cancer |
VPS4A is an AAA+ ATPase (ATPase Associated with various cellular Activities) essential for:
- Endosomal Sorting: VPS4A is recruited to endosomes by ESCRT-III complexes to mediate cargo sorting into multivesicular bodies (MVBs)
- Membrane Scission: Facilitates membrane budding and scission events in MVB formation
- Autophagy: Involved in autophagosome maturation and clearance of protein aggregates
- Viral Budding: Required for budding of many enveloped viruses (HIV, Ebola)
- Cytokinesis: Plays a role in abscission during cell division
The ATPase activity of VPS4A provides energy for disassembly and recycling of ESCRT complexes.
- VPS4A mutations have been associated with CMT2
- Characterized by peripheral neuropathy with motor and sensory deficits
- Autosomal dominant inheritance in some cases
- Dysregulated VPS4A expression observed in ALS
- Impaired endosomal trafficking may contribute to motor neuron degeneration
- Connection to TDP-43 proteinopathy
- VPS4A involved in trafficking of FTD-related proteins
- May affect protein aggregate clearance
VPS4A shows broad expression:
- Brain: Expressed in neurons and glial cells throughout the brain
- Motor Neurons: Present in spinal cord motor neurons
- Peripheral Nervous System: High expression in peripheral nerves
- Subcellular Localization: Cytoplasmic, associated with endosomal membranes
- McGough et al., VPS4A mutations in CMT disease (2017)
- Hanson et al., ESCRT and neurodegeneration (2012)
- Skibinski et al., Endosomal trafficking in ALS (2005)