MT-ND6

Chr MT

NADH dehydrogenase subunit 6

Also known as: MTND6

NCBI Gene: 4541 ENSG00000198695 UniProt: P03923 OMIM: 516006

This gene encodes a core subunit of NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial respiratory chain. Mutations cause Leber hereditary optic neuropathy (particularly the m.14484T>C variant), Leigh syndrome, dystonia, and Complex I deficiency. Inheritance is maternal through the mitochondrial genome, with clinical severity dependent on the degree of heteroplasmy.

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. Implicated in Leber hereditary optic neuropathy; Leigh disease; and spinal muscular atrophy with lower extremity predominant 2B. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeber hereditary optic neuropathy

UniProtLeber hereditary optic neuropathy with dystonia

UniProtMitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome

UniProtLeigh syndrome

Clinical highlights

Management implications

Idebenone is authorised in the EU for visual impairment in LHON.Applies when the variant causes LHON (m.11778G>A in MT-ND4, m.3460G>A in MT-ND1, m.14484T>C in MT-ND6 are the primary LHON variants); this gene's other diseases are not covered.

MT-ND6: treatable — idebenone

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

📖

GeneReview available — MT-ND6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Treatment implicationsTreatable

Leber hereditary optic neuropathy (LHON)

Applies when the variant causes LHON (m.11778G>A in MT-ND4, m.3460G>A in MT-ND1, m.14484T>C in MT-ND6 are the primary LHON variants); this gene's other diseases are not covered.

Idebenone is authorised in the EU for visual impairment in LHON.

Treatment of choice

idebenone (Raxone) — EU-authorised 2015 for age 12 and over

EMA EPAR Raxone (authorised 8 Sep 2015). Confirm with a neurologist and current guidelines. Functional class (GOF/LOF) is from published functional/segregation data, never inferred from the variant. As of 2026-10. Curated from the clinical genetics/neurology literature (cited per gene). Decision-support, not prescribing.

Nuclear-gene analyses omitted

MT-ND6 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-ND6 · protein map & ClinVar variants

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

MITOMAP Disease Variants — MT-ND6

Live table ↗

Variant	AA	Disease	Status	GenBank seqs
m.14163C>T	A171T	Possible deafness factor	Conflicting reports	15
m.14179A>G	Y165Y	Recurrent pregnancy loss	Reported	352
m.14258G>A	P139L	LHON synergistic combo 10680A + 12033G + 14258A also combo 14258A + 14582G	Reported	42
m.14263C>T	E137E	Recurrent pregnancy loss	Reported	7
m.14279G>A	S132L	LHON	Reported	7
m.14319T>C	N119D	PD, early onset	Reported	85
m.14325T>C	N117D	LHON	Reported	61
m.14340C>T	V112M	SNHL	Reported	28
m.14342C>A	G111V	Possible association with sepsis	Reported	0
m.14351T>C	E108G	SNHL + neurodevelopmental delay	Reported	2
m.14430A>G	W82R	Thyroid Cancer / Leigh Syndrome	Reported	0
m.14430A>C	W82G	Leigh Syndrome	Reported	0
m.14439G>A	P79S	LS / Mitochondrial Respiratory Chain Disorder	Reported	0
m.14441T>C	Y78C	Leigh-like phenotype	Reported	0
m.14453G>A	A74V	MELAS / Leigh Disease	Likely pathogenic · confirmed	0
m.14459G>A	A72V	LDYT / Leigh Disease / dystonia / carotid atherosclerosis risk	Pathogenic · confirmed	3
m.14465G>A	T70I	LHON / various supected mitochondrial disease	Likely pathogenic · confirmed	0
m.14482C>A	M64I	LHON	Likely pathogenic · confirmed	2
m.14482C>G	M64I	LHON	Likely pathogenic · confirmed	0
m.14484T>C	M64V	LHON	Pathogenic · confirmed	71
m.14487T>C	M63V	Dystonia / Leigh Disease / ataxia / ptosis / epilepsy	Pathogenic · confirmed	0
m.14495A>G	L60S	LHON	Likely pathogenic · confirmed	2
m.14498T>C	Y59C	LHON	Reported	0
m.14502T>C	I58V	LHON	Reported	223
m.14512TA>-	frameshift	EXIT w mild myopathy & hyperCKaemia	Likely pathogenic · confirmed	0
m.14535C>CC	frameshift	DMDF	Reported	1
m.14538A>G	F46L	LHON	Reported	0
m.14568C>T	G36S	LHON	Likely pathogenic · confirmed	6
m.14577T>C	I33V	MIDM	Reported	452
m.14582A>G	V31A	LHON synergistic combo 14258A + 14582G	Reported	364
m.14596A>T	I26M	LHON with hereditary spastic dystonia	Uncertain significance · reported	0
m.14597A>G	I26T	LHON / LS	Likely pathogenic · confirmed	0
m.14598T>C	I26V	PD / LS	Uncertain significance · reported	7
m.14600G>A	P25L	Leigh Disease w/optic atrophy / mouse model	Reported	0
m.14668C>T	M2M	Depressive disorder associated; reduced risk of esophageal cancer [D1-D2-D3-D4 marker]	Reported	2,521