MT-ND4L

Chr MT

NADH dehydrogenase subunit 4L

Also known as: MTND4L

NCBI Gene: 4539 ENSG00000212907 UniProt: P03901 OMIM: 516004

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.

OMIM ResearchSummary from Curated mito context

Enables NADH dehydrogenase (ubiquinone) activity. Predicted to be involved in mitochondrial electron transport, NADH to ubiquinone and proton motive force-driven mitochondrial ATP synthesis. Located in mitochondrial inner membrane. Part of respiratory chain complex I. Implicated in Leber hereditary optic neuropathy and diabetes mellitus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— MT-ND4L

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Gene-Disease Validity (ClinGen)

mitochondrial disease · MTLimited

Limited evidence — not for standalone diagnostic reporting

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

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

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.

MITOMAP Disease Variants — MT-ND4L

MITOMAP ↗

Variant	AA	Disease	Status	GenBank
m.10543A>G	H25R	LHON	Reported	0.000%
m.10591T>G	F41C	LHON	Reported	0.000%
m.10609T>C	M47T	Type 2 diabetes patients with underlying 3243G / LHON patient with 10663C	Reported	237.260%
m.10652T>C	I61I	BD / MDD-associated	Reported	8.730%
m.10663T>C	V65A	LHON	Cfrm [LP]	0.310%
m.10676C>G	C69W	Type 2 cataract patients with underlying 3243G	Reported	0.150%
m.10680G>A	A71T	LHON / synergistic combo 10680A + 12033G + 14258A	Reported / possibly synergistic	2.760%