NDUFV3
Chr 21NADH:ubiquinone oxidoreductase subunit V3
Also known as: CI-10k, CI-9KD
The NDUFV3 protein is an accessory subunit of mitochondrial respiratory chain Complex I (NADH dehydrogenase), which transfers electrons from NADH to ubiquinone in cellular energy production. Mutations cause mitochondrial complex I deficiency, typically presenting as a multisystem disorder affecting high-energy demanding organs including the brain, heart, and skeletal muscle with autosomal recessive inheritance. This gene is extremely intolerant to loss-of-function variants, indicating that even single functional copies are insufficient for normal cellular function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
207 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 | 84 | 0 | 84 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 77 | 12 | 0 | 89 |
Likely Benign | 0 | 10 | 4 | 6 | 20 |
Benign | 0 | 0 | 1 | 2 | 3 |
Conflicting | — | 2 | |||
| Total | 0 | 87 | 104 | 8 | 201 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NDUFV3 · 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