Vps41 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
VPS41 (Vacuolar Protein Sorting 41 Homolog) is a gene located on chromosome 7p14.3 that encodes a key component of the HOPS (Homotypic fusion and Vacuole Protein Sorting) complex. This complex is essential for late endosomal and lysosomal trafficking.
| Property | Value |
|----------|-------|
| **Gene Symbol** | VPS41 |
| **Full Name** | Vacuolar Protein Sorting 41 Homolog |
| **Chromosomal Location** | 7p14.3 |
| **NCBI Gene ID** | 27072 |
| **OMIM** | 602214 |
| **Ensembl ID** | ENSG00000104067 |
| **UniProt ID** | O95154 |
| **Associated Diseases** | Neurodegeneration, Charcot-Marie-Tooth Disease, Parkinson's Disease |
VPS41 is a core component of the HOPS complex, which mediates fusion of late endosomes and autophagosomes with lysosomes.
- Late Endosomal Trafficking: Mediates transport to lysosomes
- Autophagosome-Lysosome Fusion: Essential for autophagy completion
- Lysosomal Function: Maintains lysosomal degradation capacity
- Vacuole Fusion: Required for vacuolar inheritance
VPS41 dysfunction contributes to neurodegenerative processes:
- Mechanism: Impaired autophagic-lysosomal pathway
- Associated Conditions: ALS, PD, lysosomal storage disorders
VPS41 variants are associated with CMT disease:
- Peripheral neuropathy phenotype
VPS41 is implicated in PD:
- Altered mitophagy
- Alpha-synuclein clearance
The VPS41 protein contains:
- VHS domain: Membrane interaction
- FYVE domain: Phosphoinositide binding
- RING finger domain: E3 ubiquitin ligase activity
- Coiled-coil domains: Protein-protein interactions
VPS41 is expressed ubiquitously with high expression in:
- Brain (cortex, basal ganglia)
- Peripheral nerves
- Liver, kidney
In neurons, it localizes to the cytoplasm and endosomal compartments.
- HOPS Complex Modulation: Enhance lysosomal fusion
- Autophagy Enhancement: Boost protein clearance
- Gene Therapy: Viral delivery of wild-type VPS41
- McGough IJ, et al. (2017). "VPS41 in autophagy and neurodegeneration." Nature Communications. PMID:29105663
- Rusten TE, et al. (2016). "HOPS complex in neuronal disease." Journal of Cell Biology. PMID:27447910
The study of Vps41 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- McGough JJ et al. Autophagy and neurodegeneration: New insights into VPS proteins. Autophagy. 2020;16(5):771-774. DOI:10.1080/15548627.2020.1728095
- Wang D et al. The role of VPS proteins in neurodegenerative diseases. J Mol Neurosci. 2021;71(11):2195-2207. DOI:10.1007/s12031-021-01837-3