APOLD1
Chr 12ADapolipoprotein L domain containing 1
Also known as: BDVAS, VERGE
APOLD1 encodes a protein that modulates endothelial barrier permeability and is required for proper organization of endothelial cell-cell junctions and cytoskeleton. Mutations cause a vascular-type bleeding disorder with autosomal dominant inheritance. The gene shows low constraint to loss-of-function variation (pLI 0.0001, LOEUF 1.74).
Primary Disease Associations & Inheritance
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
114 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 | 43 | 0 | 43 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 56 | 5 | 0 | 61 |
Likely Benign | 0 | 0 | 1 | 0 | 1 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 56 | 51 | 0 | 107 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
APOLD1 · 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