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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ND2
mitochondrially encoded NADH dehydrogenase 2
Chromosome MT
NCBI Gene: 4536Ensembl: ENSG00000198763.3HGNC: HGNC:7456UniProt: P03891
78PubMed Papers
23Diseases
3Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Swiss-Prot Reviewed
Leber hereditary optic neuropathyLeigh syndromemitochondrial diseasemitochondrial complex I deficiency
✦AI Summary

ND2 (mitochondrially encoded NADH dehydrogenase 2) is a core subunit of mitochondrial Complex I that catalyzes electron transfer from NADH through the respiratory chain using ubiquinone as an electron acceptor, essential for complex I catalytic activity and assembly 1. ND2 supports mitochondrial oxidative phosphorylation and ATP synthesis, with expression patterns linked to cellular differentiation and developmental processes 2. The protective ND2 m.5178C>A mutation enhances mitochondrial functions, increasing ATP synthesis, oxygen consumption rates, and Complex I activity while decreasing reactive oxygen species production and apoptosis 3. ND2 expression shows sex-dependent regulation in human spinal cord oligodendrocytes, with higher levels in females 4, and increases during post-weaning developmental transitions in the pig cecum 5. ND2 upregulation participates in parthanatos-mediated glioma cell death through respiratory Complex I activation 6. Clinical relevance includes associations with Leber hereditary optic neuropathy, Leigh syndrome, and Alzheimer disease, though ND2 variants show no significant association with reproductive outcomes in in vitro fertilization 7. ND2 also serves as a biomarker for intervertebral disc degeneration 8.

Sources cited
1
ND2 is a core subunit of Complex I that catalyzes electron transfer from NADH and is essential for catalytic activity and assembly
PMID: 16996290
2
ND2 expression is preferentially elevated in acute myelogenous leukemia cells and decreases during myeloid differentiation
PMID: 27463352
3
The MT-ND2 m.5178C>A mutation enhances ATP synthesis, oxygen consumption, Complex I activity, and mitochondrial membrane potential while reducing ROS and apoptosis
PMID: 34336093
4
MT-ND2 expression is higher in female oligodendrocytes compared to male oligodendrocytes in human spinal cord
PMID: 38934400
5
ND2 and COX2 are upregulated during post-weaning development in the pig cecum
PMID: 38114433
6
ND2 upregulation participates in respiratory Complex I activation during parthanatos-induced glioma cell death
PMID: 37186123
7
MT-ND2 gene variants show no significant association with total fertilization failure in in vitro fertilization cycles
PMID: 29577757
8
MT-ND2 is identified as a biomarker for intervertebral disc degeneration
PMID: 35409356
Disease Associationsⓘ23
Leber hereditary optic neuropathyOpen Targets
0.70Moderate
Leigh syndromeOpen Targets
0.69Moderate
mitochondrial diseaseOpen Targets
0.67Moderate
mitochondrial complex I deficiencyOpen Targets
0.67Moderate
type 2 diabetes mellitusOpen Targets
0.61Moderate
diabetes mellitusOpen Targets
0.60Moderate
mitochondrial non-syndromic sensorineural hearing lossOpen Targets
0.58Moderate
MELAS syndromeOpen Targets
0.57Moderate
Mitochondrial non-syndromic sensorineural deafness with susceptibility to aminoglycoside exposureOpen Targets
0.56Moderate
MERRFOpen Targets
0.52Moderate
MERRF syndromeOpen Targets
0.52Moderate
Rare genetic deafnessOpen Targets
0.44Moderate
Leigh syndrome, mitochondrialOpen Targets
0.43Moderate
interstitial nephritisOpen Targets
0.42Moderate
auditory neuropathyOpen Targets
0.42Moderate
familial hypertrophic cardiomyopathyOpen Targets
0.42Moderate
polycystic ovary syndromeOpen Targets
0.42Moderate
gestational diabetesOpen Targets
0.41Moderate
Insulin resistanceOpen Targets
0.40Moderate
obesityOpen Targets
0.40Moderate
Alzheimer disease mitochondrialUniProt
Leber hereditary optic neuropathyUniProt
Leigh syndromeUniProt
Pathogenic Variants1
NC_012920.1(MT-ND2):m.4810G>ALikely pathogenic
Mitochondrial complex I deficiency|Mitochondrial disease
★★★☆2023
View on ClinVar ↗
Drug Targets3
ME-344Phase I/II
Mitochondrial complex I (NADH dehydrogenase) inhibitor
breast cancer
METFORMINApproved
Mitochondrial complex I (NADH dehydrogenase) inhibitor
diabetes mellitus
METFORMIN HYDROCHLORIDEApproved
Mitochondrial complex I (NADH dehydrogenase) inhibitor
type 2 diabetes mellitus
Related Genes
NDUFB5Protein interaction100%NDUFA13Protein interaction100%NDUFC2Protein interaction100%NDUFB3Protein interaction100%NDUFAB1Protein interaction100%NDUFS1Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Liver
89%
Brain
67%
Lung
18%
Ovary
17%
Bone Marrow
11%
Gene Interaction Network
Click a node to explore
ND2NDUFB5NDUFA13NDUFC2NDUFB3NDUFAB1NDUFS1
PROTEIN STRUCTURE
Preparing viewer…
PDB9CWT · 3.44 Å · EM
View on RCSB ↗
RankingsWhere ND2 stands among ~20K protein-coding genes
  • #6,091of 20,598
    Most Researched78
  • #622of 1,025
    FDA-Approved Drug Targets2
  • #4,971of 5,498
    Most Pathogenic Variants1
Genes detectedND2
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
Single-Cell RNA-Seq Analysis of Cells from Degenerating and Non-Degenerating Intervertebral Discs from the Same Individual Reveals New Biomarkers for Intervertebral Disc Degeneration.
PMID: 35409356
Int J Mol Sci · 2022
1.00
2
Association between sperm mitochondrial ND2 gene variants and total fertilization failure.
PMID: 29577757
Syst Biol Reprod Med · 2018
0.90
3
Protective Effect of Mitochondrial ND2 C5178A Gene Mutation on Cell and Mitochondrial Functions.
PMID: 34336093
Oxid Med Cell Longev · 2021
0.80
4
Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord.
PMID: 38934400
Neural Regen Res · 2025
0.70
5
Single-cell profiling of the pig cecum at various developmental stages.
PMID: 38114433
Zool Res · 2024
0.60