VAPB (Vesicle-Associated Membrane Protein-Associated Protein B)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">VAPB (VAMP-Associated Protein B)</th>
</tr>
<tr>
<td class="label">
Gene Symbol</td>
<td>VAPB</td>
</tr>
<tr>
<td class="label">
Full Name</td>
<td>Vesicle-Associated Membrane Protein-Associated Protein B</td>
</tr>
<tr>
<td class="label">
Chromosomal Location</td>
<td>20q13.33</td>
</tr>
<tr>
<td class="label">
NCBI Gene ID</td>
<td>9217</td>
</tr>
<tr>
<td class="label">
Ensembl ID</td>
<td>ENSG00000124194</td>
</tr>
<tr>
<td class="label">
OMIM ID</td>
<td>608627</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>O95295</td>
</tr>
<tr>
<td class="label">
Protein Name</td>
<td>VAP-B</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">37 edges</a></td>
</tr>
</table>
Introduction
...VAPB (Vesicle-Associated Membrane Protein-Associated Protein B)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">VAPB (VAMP-Associated Protein B)</th>
</tr>
<tr>
<td class="label">
Gene Symbol</td>
<td>VAPB</td>
</tr>
<tr>
<td class="label">
Full Name</td>
<td>Vesicle-Associated Membrane Protein-Associated Protein B</td>
</tr>
<tr>
<td class="label">
Chromosomal Location</td>
<td>20q13.33</td>
</tr>
<tr>
<td class="label">
NCBI Gene ID</td>
<td>9217</td>
</tr>
<tr>
<td class="label">
Ensembl ID</td>
<td>ENSG00000124194</td>
</tr>
<tr>
<td class="label">
OMIM ID</td>
<td>608627</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>O95295</td>
</tr>
<tr>
<td class="label">
Protein Name</td>
<td>VAP-B</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">37 edges</a></td>
</tr>
</table>
Introduction
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.
Overview
Mermaid diagram (expand to render)
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:
- ER homeostasis: Maintains endoplasmic reticulum function and calcium signaling
- Lipid metabolism: Regulates phospholipid synthesis and trafficking
- [Unfolded protein response](/entities/unfolded-protein-response): Coordinates ER stress responses
- Disease associations: ALS (Finkel type), spinal muscular atrophy, late-onset neurodegeneration
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["@ref"].
Gene Overview
Protein Structure
VAP-B is a 243 amino acid type III ER membrane protein:
- N-terminal MSP domain: Major sperm protein (MSP) domain - secreted and functions as a signaling molecule
- Coiled-coil domain: Protein-protein interactions
- Transmembrane domain: C-terminal ER anchor
- C-terminal FFAT domain: Binds proteins containing FFAT motifs (e.g., OSBP, CERT)
The protein forms antiparallel homodimers and can release the MSP domain via proteolytic cleavage[^2].
Normal Function
- FFAT motif interactions: Binds OSBP and CERT for lipid transfer
- Phospholipid homeostasis: Regulates phosphatidylinositol-4-phosphate (PI4P) levels
- ER-lipid droplet contact sites: Participates in lipid droplet biogenesis
ER Homeostasis
- ER morphology maintenance: Regulates ER sheet and tubule formation
- Unfolded protein response: Involved in ER stress signaling
- Calcium homeostasis: Modulates ER calcium stores
Intracellular Trafficking
- Vesicle trafficking: Regulates ER-to-Golgi transport
- [Autophagy](/mechanisms/autophagy-lysosome-neurodegeneration): Controls autophagosome formation and maturation
- Lysosomal function: Coordinates endolysosomal trafficking[^3]
Disease Associations
ALS8 (Familial ALS Type 8)
The P56S mutation (proline-to-serine at position 56) causes autosomal dominant ALS8:
- Onset: Typically 25-45 years (later than other familial ALS)
- Phenotype: Progressive limb weakness, spasticity, bulbar involvement
- Progression: Variable, often slower than sporadic ALS
- Penetrance: Incomplete - some carriers remain asymptomatic
Other variants identified:
- T46I (threonine-to-isoleucine)
- V234I (valine-to-isoleucine)[^4]
Late-Onset Spinal Muscular Atrophy
- Similar phenotype to ALS8 but without upper motor neuron signs
- Proximal muscle weakness and atrophy
- Generally benign course
Molecular Pathogenesis
VAPB mutations lead to:
ER stress: Accumulation of mutant protein disrupts ER function
Lipid dysregulation: Altered phospholipid metabolism
[Autophagy](/entities/autophagy) impairment: Defective autophagosome maturation
Mitochondrial dysfunction: Secondary mitochondrial damage
Protein aggregation: Enhanced [TDP-43](/proteins/tdp-43) pathologyAnimal Models
- VAPB P56S knock-in mice: Exhibit ER stress, autophagy defects, and age-dependent motor dysfunction
- Drosophila VAPB models: Show neurodegeneration with ER abnormalities
- C. elegans VAPB models: Reveal conserved roles in ER homeostasis[^5]
Therapeutic Approaches
- ER stress modulators: TUDCA, sodium phenylbutyrate
- Autophagy enhancers: Rapamycin, trehalose
- Lipid metabolism modulators: Small molecules targeting lipid pathways
- Gene therapy: RNAi-mediated allele-specific silencing
Background
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.
Cross-References
- [Amyotrophic Lateral Sclerosis (ALS)](/diseases/amyotrophic-lateral-sclerosis)
- [Motor Neurons](/cell-types/motor-neurons)
- [Endoplasmic Reticulum Stress](/mechanisms/endoplasmic-reticulum-stress)
- Lipid Dysregulation
- [Autophagy Lysosomal AD](/mechanisms/autophagy-lysosomal-ad)
- [Genes Index](/genes)
See Also
- [Genes Index](/genes)
- [Proteins Index](/proteins)
External Links
- [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/) — Gene database
- [OMIM](https://www.omim.org/) — Online Mendelian Inheritance in Man
Brain Atlas Resources
- [Allen Brain Atlas](https://brain-map.org)
- [Allen Human Brain Atlas: VAPB search](https://human.brain-map.org/microarray/search/show?search_term=VAPB)
- [Allen Mouse Brain Atlas: VAPB search](https://mouse.brain-map.org/search/index.html?query=VAPB)
- [Allen Cell Type Atlas](https://portal.brain-map.org/atlases-and-data/rnaseq)
- [BrainSpan Developmental Transcriptome](https://www.brainspan.org)
References
Unknown, : : (n.d.)Pathway Diagram
The following diagram shows the key molecular relationships involving VAPB (VAMP-Associated Protein B) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
Expression Profile
Sources: [GTEx Portal v10](https://gtexportal.org/home/gene/vapb) | [Allen Brain Atlas](https://www.brain-map.org/)
| Rank | Tissue | Median TPM |
|------|--------|------------|
| 1 | Brain Cerebellar Hemisphere | 36.08 |
| 2 | Brain Spinal cord cervical c-1 | 36.07 |
| 3 | Thyroid | 30.70 |
| 4 | Brain Frontal Cortex BA9 | 28.94 |
| 5 | Artery Tibial | 26.74 |
| 6 | Brain Cerebellum | 26.51 |
| 7 | Colon Sigmoid | 26.04 |
| 8 | Uterus | 25.34 |
| 9 | Artery Aorta | 24.41 |
| 10 | Nerve Tibial | 24.23 |
| 11 | Adrenal Gland | 23.80 |
| 12 | Muscle Skeletal | 23.72 |
| 13 | Artery Coronary | 23.27 |
| 14 | Esophagus Muscularis | 23.24 |
| 15 | Brain Hypothalamus | 23.15 |
Brain-Region Expression:
| Region | Median TPM |
|--------|------------|
| Brain Cerebellar Hemisphere | 36.08 |
| Brain Spinal cord cervical c-1 | 36.07 |
| Brain Frontal Cortex BA9 | 28.94 |
| Brain Cerebellum | 26.51 |
| Brain Hypothalamus | 23.15 |
| Brain Substantia nigra | 21.37 |