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.

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]

OMIM ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— MT-ND2

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Gene-Disease Validity (ClinGen)

Leigh syndrome · MTLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.89top 5%

GOF

0.6541th %ile

LOF

0.1895th %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-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

MITOMAP ↗

Variant	AA	Disease	Status	GenBank
m.4491G>A	V8I	High altitude pulmonary edema susceptibility	Reported	157.920%
m.4516G>A	G16D	Possible LHON modulator	Reported	0.000%
m.4580G>A	M37M	Protective factor for stroke risk (hg V)	Reported	169.100%
m.4611A>-	M-Term	Leigh Syndrome	Reported [VUS]	0.000%
m.4633C>G	A55G	LHON candidate	Reported	0.000%
m.4640C>A	I57M	LHON / Epilepsy	Reported	38.450%
m.4648T>C	F60S	PEG	Reported	0.150%
m.4659G>A	A64T	possible PD risk factor / LHON	Reported	17.000%
m.4681T>C	L71P	Leigh Syndrome	Reported [VUS]	0.150%
m.4769A>A	M100M	SZ-associated	Reported	200.200%
m.4810G>A	W114Term	EXIT with myalgia & ophthalmoplegia	Cfrm [LP]	0.000%
m.4831G>A	G121D	Isolated myopathy	Reported	0.150%
m.4833A>G	T122A	Diabetes helper mutation AD, PD	Reported	100.020%
m.4852T>A	L128Q	LHON	Reported	0.000%
m.4883C>T	P138P	Glaucoma	Conflicting reports	442.820%
m.4917A>G	N150D	LHON / Insulin Resistance / AMD / NRTI-PN	Reported	491.680%
m.4924G>T	S152I	Possible LHON helper (one 11778 patient)	Reported	0.000%
m.4935A>G	T156A	Lipomatosis+EXIT	Reported	0.000%
m.4944A>G	I159V	High altitude pulmonary edema susceptibility	Reported	1.530%
m.4959G>A	A164T	Possible LHON helper (one 11778 patient)	Reported	11.180%
m.4983C>T	Q172Term	Unspecified suspected mitochondrial disorder	Reported [VUS]	0.000%
m.5001A>AA	frameshift	Developmental delay, seizure, cardiomyopathy, lactic acidosis	Reported [VUS]	0.000%
m.5095T>C	I209T	Proximal muscle weakness and atrophy	Reported	2.910%
m.5133AA>-	frameshift	Exercise intolerance (EXIT)	Reported [VUS]	0.000%
m.5153A>G	L228L	Recurrent pregnancy loss	Reported	54.070%
m.5178C>A	L237M	Longevity / Extraversion / diabetes / AMS protection / blood iron metabolism / correlation with myocardial infarction / atherosclerosis	Reported	439.760%
m.5182C>T	T238M	Dilated cardiomyopathy / pseudoexfoliation glaucoma	Conflicting reports	0.000%
m.5244G>A	G259S	LHON	Reported [VUS]	0.000%
m.5367ACCTCAATCACACTACTCC>-	frameshift	Unspecified suspected mitochondrial disorder	Reported [VUS]	0.000%
m.5452C>T	T328M	Progressive Encephalomyopathy	Reported	3.060%
m.5460G>A	A331T	AD / PD / LHON / PCOS patients	Conflicting reports	719.450%
m.5460G>T	A331S	AD	Reported	0.000%