MT-ND1

Chr MT

NADH dehydrogenase subunit 1

Also known as: MTND1

NCBI Gene: 4535ENSG00000198888UniProt: P03886

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]

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
191
ClinVar variants
13
Pathogenic / LP
—
pLI score
0
Active trials
Clinical Summary— MT-ND1
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · MTDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 79 VUS of 191 total submissions

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

191 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic10
VUS79
Likely Benign50
Benign48
Conflicting1
3
Pathogenic
10
Likely Pathogenic
79
VUS
50
Likely Benign
48
Benign
1
Conflicting

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————3
Likely Pathogenic
————10
VUS
————79
Likely Benign
————50
Benign
————48
Conflicting
—1
Total—191

Counts from ClinVar esearch · Updated hourly

View in 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.

Gene2Phenotype Curations

MT-ND1-related Leber hereditary optic neuropathy

definitive
Mito.UndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — MT-ND1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy.
Liu K et al.·Autophagy
2022
Gene therapy for Leber hereditary optic neuropathy.
Battista M et al.·Expert Opin Biol Ther
2024Review
Digenic Leigh syndrome on the background of the m.11778G>A Leber hereditary optic neuropathy variant.
Blickhäuser B et al.·Brain
2024
The m.3890G>A/MT-ND1 mtDNA rare pathogenic variant: Expanding clinical and MRI phenotypes.
Vacchiano V et al.·Mitochondrion
2021Case report
De novo frameshift variant in MT-ND1 causes a mitochondrial complex I deficiency associated with MELAS syndrome.
Lou X et al.·Gene
2023
Analysis of Inherited Optic Neuropathies.
Lazdinyte S et al.·Klin Monbl Augenheilkd
2019
First mitochondrial genome-wide association study with metabolomics.
Aboulmaouahib B et al.·Hum Mol Genet
2022
Glioma grade and mortality in relation to sequence variation in the mitochondrial genome.
Peeri NC et al.·Cancer Genet
2025
Leber's hereditary optic neuropathy: Current approaches and future perspectives on Mesenchymal stem cell-mediated rescue.
Mohana Devi S et al.·Mitochondrion
2021Review
Genetic and clinical evidence of mitochondrial dysfunction in autism spectrum disorder and intellectual disability.
Valiente-Pallejà A et al.·Hum Mol Genet
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools