MT-ND3

Chr MT

NADH dehydrogenase subunit 3

Also known as: MTND3

NCBI Gene: 4537 ENSG00000198840 UniProt: P03897

This gene encodes a core subunit of NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial respiratory chain, which transfers electrons from NADH to ubiquinone during oxidative phosphorylation. Mutations cause Leigh syndrome and Complex I deficiency, with clinical severity depending on the degree of heteroplasmy. Inheritance follows a maternal pattern due to its location in the mitochondrial genome.

GeneReviews ResearchSummary from Curated mito context

Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone. Located in mitochondrial inner membrane. Part of respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and Parkinson's disease. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— MT-ND3

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Gene-Disease Validity (ClinGen)

mitochondrial disease · MTDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 20 VUS of 52 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MT-ND3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.86top 5%

GOF

0.72top 25%

LOF

0.11100th %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

52 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic2

VUS20

Likely Benign14

Benign11

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	—	—	—	—	3
Likely Pathogenic	—	—	—	—	2
VUS	—	—	—	—	20
Likely Benign	—	—	—	—	14
Benign	—	—	—	—	11
Conflicting	—				1
Total	—				51

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

18 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap MT-ND3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MT-ND3 · protein map & ClinVar variants

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

MITOMAP Disease Variants — MT-ND3

MITOMAP ↗

Variant	AA	Disease	Status	GenBank
m.10086A>G	N10D	Hypertensive end-stage renal disease	Reported	79.040%
m.10134C>A	Q26K	Leigh Disease	Reported [VUS]	0.000%
m.10142C>T	N28N	Recurrent pregnancy loss	Reported	112.280%
m.10158T>C	S34P	Leigh Disease / MELAS / mito encephalomyopathy	Cfrm [P]	0.000%
m.10189T>C	M44T	Behavior alteration with dilated cardiomyopathy	Reported	0.150%
m.10191T>C	S45P	Leigh Disease / ESOC	Cfrm [P]	0.000%
m.10197G>C	A47P	Leigh Disease	Reported	0.000%
m.10197G>A	A47T	Leigh Disease / Dystonia / Stroke / LDYT	Cfrm [P]	0.460%
m.10237T>C	I60T	LHON	Reported	16.080%
m.10254G>A	D66N	Leigh Disease	Cfrm [LP]	0.000%
m.10350C>A	L98M	LHON	Reported	0.000%
m.10372A>G	E105G	Sensorimotor axonal polyneuropathy	Reported	0.000%
m.10398A>A	T114T	Invasive Breast Cancer risk factor AD PD BD lithium response Type 2 DM	Reported; lineage N marker except hg IJK	5683.760%
m.10398A>G	T114A	PD protective factor / longevity / altered cell pH / metabolic syndrome / breast cancer risk / Leigh Syndrome risk / ADHD / cognitive decline / SCA2 age of onset / Fuchs endothelial corneal dystrophy	Reported; lineage L & M marker, also hg IJK	4311.180%