MT-ND4
Chr MTNADH dehydrogenase subunit 4
Also known as: MTND4
This gene encodes a subunit of NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial respiratory chain. Mutations cause MELAS, Leigh syndrome, and Leber hereditary optic neuropathy (LHON), with m.11778G>A being the most common LHON mutation. Inheritance is maternal through mitochondrial DNA, and disease severity depends on the degree of heteroplasmy in affected tissues.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
Constraint data not available from gnomAD.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MT-ND4 · 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