VAPB (VAMP-Associated Protein B)

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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)

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

Lipid Metabolism Regulation

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) pathology

Animal 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)

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/)

GTEx Tissue Expression (median TPM)

| 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 |

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VAPB (VAMP-Associated Protein B)

VAPB (Vesicle-Associated Membrane Protein-Associated Protein B)

Introduction

VAPB (Vesicle-Associated Membrane Protein-Associated Protein B)

Introduction

Overview

Gene Overview

Protein Structure

Normal Function

Lipid Metabolism Regulation

ER Homeostasis

Intracellular Trafficking

Disease Associations

ALS8 (Familial ALS Type 8)

Late-Onset Spinal Muscular Atrophy

Molecular Pathogenesis

Animal Models

Therapeutic Approaches

Background

Cross-References

See Also

External Links

Brain Atlas Resources

References

Pathway Diagram

Expression Profile

GTEx Tissue Expression (median TPM)