VAPB
Chr 20ADVAMP associated protein B and C
Also known as: ALS8, VAMP-B, VAP-B
VAPB encodes an endoplasmic reticulum-anchored protein that mediates contact sites between the ER and endosomes, participates in the unfolded protein response, and regulates cellular calcium homeostasis. Mutations cause late-onset motor neuron diseases including amyotrophic lateral sclerosis 8 and spinal muscular atrophy (Finkel type), with inheritance following an autosomal dominant pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.559).
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
VAPB · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools