MT-ND1

Chr MT

NADH dehydrogenase subunit 1

Also known as: MTND1

NCBI Gene: 4535 ENSG00000198888 UniProt: P03886 OMIM: 516000

This gene encodes a core subunit of NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial respiratory chain, essential for cellular energy production through oxidative phosphorylation. Mutations cause MELAS, Leigh syndrome, Leber hereditary optic neuropathy (LHON), and isolated Complex I deficiency. Inheritance is maternal through the mitochondrial genome, and disease severity depends on the level 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 several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeber hereditary optic neuropathy

UniProtMitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome

UniProtAlzheimer disease mitochondrial

UniProtType 2 diabetes mellitus

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-ND1: 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-ND1

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-ND1 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

Tap or hover a gene, landmark or tick; genes open their page, ticks their variant.

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-ND1 · protein map & ClinVar variants

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

MITOMAP Disease Variants — MT-ND1

Live table ↗

Variant	AA	Disease	Status	GenBank seqs
m.3308T>G	M1Term	Sudden Infant Death	Reported	6
m.3308T>C	M1T	MELAS / DEAF enhancer / hypertension / LVNC / putative LHON	Reported	498
m.3310C>T	P2S	Diabetes / HCM	Reported	13
m.3316G>A	A4T	Diabetes / LHON / PEO / vascular dementia	Reported	646
m.3335T>C	I10T	LHON	Reported	68
m.3336T>C	I10I	Carotid atherosclerosis risk	Reported	240
m.3337G>A	V11M	Cardiomyopathy	Reported	111
m.3340C>T	P12S	Encephaloneuromyopathy	Reported	3
m.3365T>C	L20P	EXIT	Reported	0
m.3376G>A	E24K	LHON MELAS overlap	Uncertain significance · confirmed	0
m.3380G>A	R25Q	MELAS	Uncertain significance · reported	2
m.3388C>A	L28M	Materally Inherited Nonsyndromic Deafness	Reported	30
m.3391G>A	G29S	LHON	Reported	56
m.3394T>C	Y30H	LHON / Diabetes / CPTdeficiency / high altitude adaptation	Uncertain significance · reported	860
m.3395A>G	Y30C	LHON / HCM with hearing loss	Reported	29
m.3396T>C	Y30Y	NSHL / MIDD	Reported	625
m.3397A>G	M31V	ADPD / possibly LVNC-cardiomyopathy associated / resistance to high altitude pulmonary edema	Reported	179
m.3398T>C	M31T	DMDF+HCM / GDM / possibly LVNC cardiomyopathy-associated	Reported	317
m.3399A>T	M31I	Gestational Diabetes (GDM)	Reported	55
m.3407G>A	R34H	HCM / Muscle involvement	Conflicting reports	1
m.3418A>G	N38D	AMegL	Reported	1
m.3421G>A	V39I	MIDD	Reported	92
m.3437G>A	G44E	Mitochondrial myopathy, EXIT	Reported	0
m.3457G>A	D51N	LS+HCM	Reported	0
m.3460G>A	A52T	LHON	Pathogenic · confirmed	31
m.3461C>T	A52V	LHON	Reported	0
m.3472T>C	F56L	LHON	Reported	5
m.3481G>A	E59K	MELAS / Progressive Encephalomyopathy	Uncertain significance · confirmed	0
m.3482A>G	E59G	MELAS/LS overlap	Reported	0
m.3488T>C	L61P	LHON	Reported	1
m.3496G>T	A64S	LHON	Reported	11
m.3497C>T	A64V	LHON	Reported	218
m.3502T>C	S66P	MELAS / MM w reversible COX deficiency	Uncertain significance · reported	0
m.3548T>C	I81T	Possible LHON helper (one 14484 patient)	Reported	37
m.3551C>T	A82V	LHON	Reported	0
m.3552T>A	A82A	Resistance to high altitude pulmonary edema (HAPE) / matrilineal hypertension	Reported	2,193
m.3571C>-	frameshift	Mitochondrial myopathy with reversible cytochrome C oxidase deficiency	Likely pathogenic · confirmed	0
m.3571C>T	L89F	Possible LHON helper mut / idiopathic epilepsy	Reported	142
m.3632C>T	S109F	LHON	Reported	0
m.3634A>G	S110G	LHON	Reported	0
m.3635G>A	S110N	LHON	Likely pathogenic · confirmed	9
m.3644T>C	V113A	BD-associated	Reported	236
m.3667T>G	W121G	Peripheral neuropathy of T2 diabetes	Reported	0
m.3685T>C	Y127H	Leigh Syndrome	Uncertain significance · reported	0
m.3688G>A	A128T	Leigh Syndrome	Likely pathogenic · confirmed	1
m.3697G>A	G131S	MELAS / Leigh Syndrome / LDYT / BSN	Likely pathogenic · confirmed	0
m.3700G>A	A132T	LHON	Uncertain significance · confirmed	3
m.3713T>C	V136A	LHON	Reported	0
m.3733G>C	E143Q	LHON	Reported	0
m.3733G>A	E143K	LHON	Uncertain significance · confirmed	2
m.3734A>G	E143G	LHON	Uncertain significance · reported	1
m.3736G>A	V144I	LHON	Reported	115
m.3745G>A	A147T	LHON / high altitude variant	Reported	131
m.3761C>A	S152Term	Deafness w relapsing/remitting neurological symptoms	Uncertain significance · reported	0
m.3769C>G	L155V	LHON	Reported	0
m.3781T>C	S159P	LHON	Reported	0
m.3796A>G	T164A	Adult-Onset Dystonia	Reported	304
m.3833T>A	L176Q	PEG	Reported	0
m.3861A>C	W185C	SNHL + neurodevelopmental delay	Reported	0
m.3866T>C	I187T	LHON + limb claudication	Reported	240
m.3890G>A	R195Q	Progressive Encephalomyopathy / Leigh Syndrome / Optic Atrophy	Likely pathogenic · confirmed	1
m.3902ACCTTGC>GCAAGGT	DLA-GKV	EXIT+myalgia / severe LA+cardiac / 3-MGA aciduria / nephropathy+deafness+diabetes	Likely pathogenic · confirmed	0
m.3911A>G	E202G	Multisystemic disorder with SNHL and neurodevelopmental delay	Reported	0
m.3919T>C	S205P	LHON	Reported	0
m.3945C>A	I213M	Leigh-like phenotype	Reported	0
m.3946G>A	E214K	MELAS	Likely pathogenic · confirmed	1
m.3949T>C	Y215H	MELAS	Uncertain significance · reported	1
m.3955G>A	A217T	Leigh Syndrome	Reported	0
m.3958G>A	G218S	LHON	Reported	0
m.3959G>A	G218D	MELAS	Reported	0
m.3995A>G	N230S	MELAS	Reported	21
m.4081T>C	F259L	LHON	Reported	1
m.4115T>C	F270S	Possible LHON helper (one 11778 patient)	Reported	0
m.4123A>T	I273F	LHON	Reported	0
m.4132G>A	A276T	NAION-associated	Uncertain significance · reported	9
m.4135T>C	Y277H	LHON	Reported	27
m.4136A>G	Y277C	LHON	Reported	78
m.4142G>A	R279Q	Developmental delay, seizure, hypotonia	Uncertain significance · reported	0
m.4142G>T	R279L	Leigh Syndrome	Reported	0
m.4160T>C	L285P	LHON / LHON plus	Reported	1
m.4163T>C	M286T	LHON	Reported	1
m.4171C>A	L289M	LHON / Leigh-like phenotype	Uncertain significance · confirmed	2
m.4175G>A	W290Term	EXIT	Reported	0
m.4216T>C	Y304H	LHON / Insulin Resistance /possible adaptive high altitude variant / miscarriage	Conflicting reports	6,678