VAT1
Chr 17vesicle amine transport 1
Also known as: MIB, VAT-1, VATI
VAT1 encodes a multifunctional protein that functions as a NADPH-dependent quinone oxidoreductase and mediates transfer of negatively charged phospholipids between endoplasmic reticulum and mitochondrial membranes, while also regulating mitochondrial fusion through interaction with mitofusins. The gene has a low probability of loss-of-function intolerance (pLI = 0.005) and high loss-of-function observed/expected upper bound fraction (LOEUF = 0.837), with pathogenic variants predicted to act through a gain-of-function mechanism. No specific neurogenetic diseases have been definitively associated with VAT1 mutations in the provided data.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function 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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
70 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 6 | 0 | 6 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 50 | 2 | 0 | 52 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 52 | 8 | 0 | 60 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
VAT1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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