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.

GeneReviews 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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeber hereditary optic neuropathy

Clinical highlights

Gene–disease validity (ClinGen)

Limited · mitochondrial disease · MT · ClinGen 2025

not for standalone diagnostic reporting

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — MT-ND4L

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Nuclear-gene analyses omitted

MT-ND4L is a mitochondrial protein-coding gene. gnomAD constraint, carrier burden and exome coverage, the ClinVar type breakdown, AlphaFold and transcript-architecture views are built for nuclear genes and are not shown. Population data for mtDNA variants (gnomAD v3.1, homoplasmy and heteroplasmy) is on each variant page.

Where it sits in the mitochondrial genome

Tap or hover a gene, landmark or tick; genes open their page, ticks their variant.

proteinrRNAtRNAouter ring H-strand · inner L-strandMITOMAP confirmedreported (as of 2026-10-07)

37 genes from Ensembl (rCRS numbering, matched to MITOMAP’s Gene Loci); landmarks and disease alleles from MITOMAP (CC BY 3.0). Circular layout after MitoWheel.

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

Live table ↗

Variant	AA	Disease	Status	GenBank seqs
m.10543A>G	H25R	LHON	Reported	0
m.10591T>G	F41C	LHON	Reported	0
m.10609T>C	M47T	Type 2 diabetes patients with underlying 3243G / LHON patient with 10663C	Reported	1,549
m.10652T>C	I61I	BD / MDD-associated	Reported	61
m.10663T>C	V65A	LHON	Likely pathogenic · confirmed	2
m.10676C>G	C69W	Type 2 cataract patients with underlying 3243G	Reported	1
m.10680G>A	A71T	LHON / synergistic combo 10680A + 12033G + 14258A	Reported	18