MT-ND5

Chr MT

NADH dehydrogenase subunit 5

Also known as: MTND5

NCBI Gene: 4540 ENSG00000198786 UniProt: P03915 OMIM: 516005

This gene encodes a core subunit of NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial respiratory chain. Mutations cause mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), Leber hereditary optic neuropathy (LHON), Leigh syndrome, and isolated Complex I deficiency. Inheritance is maternal, 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; Leigh disease; and MELAS syndrome. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeber hereditary optic neuropathy

UniProtLeigh syndrome

UniProtMitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes 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-ND5

Authoritative clinical overview · Recommended first read

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Nuclear-gene analyses omitted

MT-ND5 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-ND5 · protein map & ClinVar variants

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

MITOMAP Disease Variants — MT-ND5

Live table ↗

Variant	AA	Disease	Status	GenBank seqs
m.12338T>C	M1T	DEAF1555 increased penetrance / LHON / MIDD	Conflicting reports	230
m.12350C>A	T5N	SNHL + neurodevelopmental delay	Reported	0
m.12361A>G	T9A	Non-alcoholic fatty liver disease	Reported	438
m.12372G>A	L12L	Altered brain pH / sCJD patients; AD risk in certain haplogroups	Benign · reported	8,848
m.12397A>G	T21A	PD, early onset	Reported	405
m.12414T>-	frameshift	EXIT	Reported	0
m.12425A>-	frameshift	Mitochondrial myopathy & renal failure	Likely pathogenic · confirmed	2
m.12477T>C	S47S	Possible HCM susceptibility / PCOS patients	Reported	361
m.12622G>A	V96I	Leigh Disease	Conflicting reports	11
m.12631T>A	S99T	found in 2 sCJD patients	Reported	0
m.12634A>G	I100V	Thyroid Cancer Cell Line	Reported	251
m.12635T>C	I100T	Suspected Leigh Disease	Reported	2
m.12662A>G	N109S	Recurrent pregnancy loss	Reported	86
m.12686T>A	F117Y	Dilated Cardiomyopathy	Reported	0
m.12705C>T	I123I	Possible protective factor for normal tension glaucoma	Reported	27,627
m.12706T>C	F124L	Leigh Disease	Likely pathogenic · confirmed	0
m.12770A>G	E145G	MELAS	Uncertain significance · reported	1
m.12778G>C	G148R	Dilated Cardiomyopathy	Reported	0
m.12782T>G	I149S	LHON	Reported	0
m.12811T>C	Y159H	Possible LHON factor	Benign · reported	741
m.12814G>T	A160S	LHON	Reported	13
m.12848C>T	A171V	LHON	Uncertain significance · reported	0
m.12858C>A	Y174Term	Unspecified suspected mitochondrial disorder	Reported	0
m.12923G>A	W196Term	LHON/MELAS/LS	Reported	0
m.12955A>G	N207D	EXIT and developmental delay	Reported	0
m.13042G>A	A236T	Optic neuropathy/ retinopathy/ LD	Likely pathogenic · confirmed	2
m.13045A>G	M237V	MELAS	Reported	0
m.13045A>C	M237L	MELAS / LHON / Leigh overlap syndrome	Uncertain significance · reported	1
m.13046T>C	M237T	LHON/MELAS overlap syndrome	Likely pathogenic · confirmed	0
m.13051G>A	G239S	LHON	Uncertain significance · confirmed	0
m.13063G>A	V243I	Adult-onset Encephalopathy / Ataxia	Uncertain significance · reported	2
m.13084A>T	S250C	MELAS / Leigh Disease	Uncertain significance · reported	0
m.13091T>C	M252T	MELAS+Migraine	Reported	0
m.13094T>C	V253A	Ataxia+PEO / MELAS, LD, LHON, myoclonus, fatigue	Pathogenic · confirmed	1
m.13112T>C	L259S	Leigh Disease	Reported	0
m.13135G>A	A267T	Possible HCM susceptibility / PCOS patients	Reported	663
m.13138G>A	E268K	Possible LHON modulator	Reported	0
m.13204G>A	V290I	Peripheral neuropathy of T2 diabetes	Reported	46
m.13268G>A	G311E	Possible ROS inducer-triggered lung cancer cell death	Reported	0
m.13271T>C	L312P	Exercise intolerance (EXIT)	Reported	1
m.13276A>G	M314V	MIDD+retinopathy	Conflicting reports	1,959
m.13289G>A	G318D	MELAS	Reported	0
m.13340T>C	F335S	LHON	Reported	3
m.13345G>A	A337T	LHON	Reported	0
m.13376T>C	I347T	MELAS w medial temporal lobe atrophy	Reported	2
m.13379A>G	H348R	LHON	Uncertain significance · confirmed	0
m.13379A>C	H348P	LHON	Uncertain significance · reported	0
m.13511A>T	K392M	Leigh-like syndrome	Reported	0
m.13513G>A	D393N	Leigh Disease / MELAS / LHON-MELAS Overlap Syndrome / negative association w Carotid Atherosclerosis	Pathogenic · confirmed	1
m.13514A>G	D393G	Leigh Disease / MELAS / Ca2+ downregulation	Likely pathogenic · confirmed	0
m.13528A>G	T398A	LHON-like, LHON, MELAS	Likely benign · reported	78
m.13565C>T	S410F	Found in MELAS patient	Reported	78
m.13580C>G	A415G	Thyroid Cancer	Reported	0
m.13590G>A	L418L	Possible protective factor for high altitude sickness / PCOS patient	Reported	3,917
m.13615A>G	I427V	LHON	Reported	11
m.13637A>G	Q434R	Possible LHON factor	Reported	612
m.13702C>G	R456G	Possible LHON helper (one 14484 patient)	Reported	20
m.13708G>A	A458T	LHON / Increased MS risk / higher freq in PD-ADS / PCOS patient / hypothyroidism	Conflicting reports	4,893
m.13712C>T	A459V	Possible LHON helper (one 11778 patient)	Reported	11
m.13730G>A	G465E	LHON	Uncertain significance · reported	0
m.13759G>A	A475T	Possible LHON factor	Reported	2,310
m.13831C>A	L499M	Thyroid Cancer Cell Line	Reported	3
m.13849A>C	N505H	MELAS	Reported	3
m.13966A>G	T544A	Greater risk with hg X of end-stage kidney disease	Reported	903
m.13967C>T	T544M	Possible LHON factor	Reported	208
m.14002A>G	T556A	High altitude pulmonary edema susceptibility	Reported	151
m.14063T>C	I576T	Potentially functional variant cosegregating with LHON3635A	Reported	26
m.14091A>T	K585N	Developmental delay, seizure, hearing loss, diabetes	Reported	0