BNIP3
Chr 10BCL2 interacting protein 3
Also known as: HABON, NIP3
This gene encodes a mitochondrial pro-apoptotic protein that induces cell death by overcoming BCL2 suppression and participates in mitochondrial quality control by facilitating degradation of damaged mitochondrial proteins. The gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF 1.46), suggesting loss of function is well-tolerated in the general population. No established Mendelian diseases have been definitively linked to BNIP3 mutations in the pediatric population.
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 (dominant-negative and gain-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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
135 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 | 91 | 0 | 91 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 23 | 10 | 0 | 33 |
Likely Benign | 0 | 0 | 1 | 0 | 1 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 23 | 107 | 0 | 130 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
BNIP3 · 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
External Resources
Links to major genomics databases and tools