MT-ND4L

Chr MT

NADH dehydrogenase subunit 4L

Also known as: MTND4L

This gene encodes a subunit of NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial respiratory chain. Mutations cause Leber hereditary optic neuropathy (LHON) and Complex I deficiency. Inheritance is maternal through mitochondrial DNA, with clinical manifestations dependent on heteroplasmy levels.

OMIMResearchSummary from Curated mito context
Multiplemechanism
Clinical SummaryMT-ND4L
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Gene-Disease Validity (ClinGen)
mitochondrial disease · MTLimited

Limited evidence — not for standalone diagnostic reporting

Population Genetics & Constraint

Constraint data not available from gnomAD.

DN
0.91top 5%
GOF
0.80top 10%
LOF
0.1299th %ile

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.

DNprediction above median
GOFprediction above median

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-ND4L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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