MT-ND4

Chr MT

NADH dehydrogenase subunit 4

Also known as: MTND4

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; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

UniProtLeber hereditary optic neuropathy
UniProtLeber hereditary optic neuropathy with dystonia
UniProtMitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome
171
ClinVar variants
23
Pathogenic / LP
pLI score
0
Active trials
Clinical SummaryMT-ND4
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · MTDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 63 VUS of 171 total submissions

Population Genetics & Constraint

Constraint data not available from gnomAD.

ClinVar Variant Classifications

171 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic3
VUS63
Likely Benign38
Benign47
20
Pathogenic
3
Likely Pathogenic
63
VUS
38
Likely Benign
47
Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
Likely Pathogenic
3
VUS
63
Likely Benign
38
Benign
47
Total171

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MT-ND4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MT-ND4-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

📖
GeneReview available — MT-ND4
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Gene therapy for Leber hereditary optic neuropathy.
Battista M et al.·Expert Opin Biol Ther
2024Review
Developments in the Treatment of Leber Hereditary Optic Neuropathy.
Chen BS et al.·Curr Neurol Neurosci Rep
2022Review
Top 10 resultsSearch PubMed ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →