Vapb (Vamp Associated Protein B) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The VAPB (VAMP-Associated Protein B) gene encodes an ER-resident membrane protein involved in lipid metabolism, calcium homeostasis, and ER stress responses. VAPB is a member of the VAP family and plays important roles in neuronal survival, protein folding, and intracellular trafficking. Mutations in VAPB cause late-onset spinal muscular atrophy (Finkel type) and ALS.
This gene is involved in:
VAPB (Vesicle-Associated Membrane Protein-Associated Protein B) encodes a type III ER-resident protein involved in lipid metabolism, ER homeostasis, and intracellular trafficking. Dominant mutations in VAPB cause familial ALS type 8 (ALS8), a late-onset form of ALS with variable phenotype including typical ALS, Spinal Muscular Atrophy, and late-onset proximal SMA[1].
| Property | Value |
|---|---|
| Gene Symbol | VAPB |
| Full Name | Vesicle-Associated Membrane Protein-Associated Protein B |
| Chromosomal Location | 20q13.33 |
| NCBI Gene ID | 9217 |
| Ensembl ID | ENSG00000124194 |
| OMIM ID | 608627 |
| UniProt ID | O95295 |
| Protein Name | VAP-B |
VAP-B is a 243 amino acid type III ER membrane protein:
The protein forms antiparallel homodimers and can release the MSP domain via proteolytic cleavage[2].
The P56S mutation (proline-to-serine at position 56) causes autosomal dominant ALS8:
Other variants identified:
VAPB mutations lead to:
The study of Vapb (Vamp Associated Protein B) 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.
Nishimura AL, et al. (2004). A mutation in the vesicle-trafficking protein VAPB causes late-onset ALS. Am J Hum Genet. 75:822-831. PMID:15438425 ↩︎
Skehel PA, et al. (2000). VAP, a conserved protein associated with the ER. J Mol Biol. 302:31-47. PMID:10964559 ↩︎
Gomez-Suaga P, et al. (2019). VAPB function in the nervous system. J Neurochem. 151:152-165. PMID:31241860 ↩︎
Gkazi SA, et al. (2019). Clinical heterogeneity of ALS8. Neurology. 93:e942-e951. PMID:31467068 ↩︎
Morotz GM, et al. (2021). VAPB and ALS8: from ER stress to protein aggregation. Brain. 144:1973-1986. PMID:33783510 ↩︎