MT-ND2

Chr MT

NADH dehydrogenase subunit 2

Also known as: MTND2

NCBI Gene: 4536 ENSG00000198763 UniProt: P03891 OMIM: 516001

This gene encodes a core subunit of NADH:ubiquinone oxidoreductase (Complex I), which catalyzes the first step of the mitochondrial electron transport chain. Mutations cause MELAS, Leigh syndrome, Leber hereditary optic neuropathy, and isolated Complex I deficiency. Inheritance is maternal through mitochondrial DNA, and clinical severity depends on the degree of heteroplasmy in affected tissues.

GeneReviews OMIM ResearchSummary from Curated mito context

Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Part of respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeber hereditary optic neuropathy

UniProtAlzheimer disease mitochondrial

UniProtLeigh syndrome

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — MT-ND2

Authoritative clinical overview · Recommended first read

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Nuclear-gene analyses omitted

MT-ND2 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

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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-ND2 · protein map & ClinVar variants

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

MITOMAP Disease Variants — MT-ND2

Live table ↗

Variant	AA	Disease	Status	GenBank seqs
m.4491G>A	V8I	High altitude pulmonary edema susceptibility	Reported	1,034
m.4516G>A	G16D	Possible LHON modulator	Reported	0
m.4580G>A	M37M	Protective factor for stroke risk (hg V)	Reported	1,106
m.4611A>-	M-Term	Leigh Syndrome	Uncertain significance · reported	0
m.4633C>G	A55G	LHON candidate	Reported	0
m.4640C>A	I57M	LHON / Epilepsy	Reported	251
m.4648T>C	F60S	PEG	Reported	1
m.4659G>A	A64T	possible PD risk factor / LHON	Reported	112
m.4681T>C	L71P	Leigh Syndrome	Uncertain significance · reported	1
m.4769A>A	M100M	SZ-associated	Reported	1,318
m.4810G>A	W114Term	EXIT with myalgia & ophthalmoplegia	Likely pathogenic · confirmed	0
m.4831G>A	G121D	Isolated myopathy	Reported	1
m.4833A>G	T122A	Diabetes helper mutation AD, PD	Reported	653
m.4852T>A	L128Q	LHON	Reported	0
m.4883C>T	P138P	Glaucoma	Conflicting reports	2,895
m.4917A>G	N150D	LHON / Insulin Resistance / AMD / NRTI-PN	Reported	3,223
m.4924G>T	S152I	Possible LHON helper (one 11778 patient)	Reported	0
m.4935A>G	T156A	Lipomatosis+EXIT	Reported	0
m.4944A>G	I159V	High altitude pulmonary edema susceptibility	Reported	10
m.4959G>A	A164T	Possible LHON helper (one 11778 patient)	Reported	75
m.4983C>T	Q172Term	Unspecified suspected mitochondrial disorder	Uncertain significance · reported	0
m.5001A>AA	frameshift	Developmental delay, seizure, cardiomyopathy, lactic acidosis	Uncertain significance · reported	0
m.5095T>C	I209T	Proximal muscle weakness and atrophy	Reported	20
m.5133AA>-	frameshift	Exercise intolerance (EXIT)	Uncertain significance · reported	0
m.5153A>G	L228L	Recurrent pregnancy loss	Reported	374
m.5178C>A	L237M	Longevity / Extraversion / diabetes / AMS protection / blood iron metabolism / correlation with myocardial infarction / atherosclerosis	Reported	2,875
m.5182C>T	T238M	Dilated cardiomyopathy / pseudoexfoliation glaucoma	Conflicting reports	0
m.5244G>A	G259S	LHON	Uncertain significance · reported	0
m.5367ACCTCAATCACACTACTCC>-	frameshift	Unspecified suspected mitochondrial disorder	Uncertain significance · reported	0
m.5452C>T	T328M	Progressive Encephalomyopathy	Reported	20
m.5460G>A	A331T	AD / PD / LHON / PCOS patients	Conflicting reports	4,903
m.5460G>T	A331S	AD	Reported	0