NDUFA2: A Core Subunit of Mitochondrial Complex I
Essential for Oxidative Phosphorylation and Linked to Mitochondrial Disease
Gene Information Card
| Symbol | NDUFA2 |
|---|---|
| Full Name | NADH:ubiquinone oxidoreductase subunit A2 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.3 |
| NCBI Gene ID | 4695 ncbi.nlm.nih.gov/gene/4695 |
| Ensembl ID | ENSG00000131495 |
| UniProt ID | O43678 |
| OMIM ID | 603834 |
| HGNC ID | 7685 |
| Aliases | CI-B8, B8, MC1DN8, NADH-ubiquinone oxidoreductase B8 subunit |
Description
The NDUFA2 gene encodes a core subunit of mitochondrial NADH:ubiquinone oxidoreductase (Complex I), the first enzyme of the electron transport chain. This subunit is essential for Complex I assembly and activity, facilitating electron transfer from NADH to ubiquinone and contributing to the proton gradient driving ATP synthesis. Mutations in NDUFA2 are associated with mitochondrial complex I deficiency and Leigh syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex I deficiency, nuclear type 8 (MC1DN8) | Loss-of-function mutations impair Complex I assembly and activity, reducing ATP production and increasing oxidative stress. | OMIM #618241; ClinVar; multiple case reports |
| Leigh syndrome | Biallelic NDUFA2 mutations disrupt mitochondrial energy metabolism, leading to neurodegeneration and characteristic brain lesions. | OMIM #256000; case studies in NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | High |
| Skeletal Muscle | 10.2 | High |
| Liver | 8.1 | Medium |
| Brain | 7.5 | Medium |
| Kidney | 6.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.3 | High expression |
| HEK293 | 11.8 | High expression |
| K562 | 9.5 | Medium expression |
| HepG2 | 8.2 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.272A>G (p.Tyr91Cys) | Missense | Rare | Reduces Complex I assembly and activity; associated with Leigh syndrome |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; causes severe Complex I deficiency |
| c.346C>T (p.Arg116*) | Nonsense | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most NDUFA2 mutations are loss-of-function, impairing Complex I assembly and activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects documented; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
| • NADH dehydrogenase (ubiquinone) activity | • mitochondrial electron transport |
| • NADH to ubiquinone | • mitochondrial respiratory chain complex I assembly |
| • oxidation-reduction process |
Pathways
• Oxidative phosphorylation (KEGG: hsa00190)
• Electron transport chain (Reactome: R-HSA-611105)
Protein Summary
NDUFA2 (also known as CI-B8) is a 98-amino-acid protein that forms part of the peripheral arm of mitochondrial Complex I. It is essential for the proper assembly and stability of the holoenzyme. The protein contains a conserved domain that interacts with other subunits to facilitate electron transfer. Defects in NDUFA2 lead to mitochondrial dysfunction, particularly in high-energy-demand tissues such as brain and muscle.
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