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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NDUFA5
NADH:ubiquinone oxidoreductase subunit A5
Chromosome 7 · 7q31.32
NCBI Gene: 4698Ensembl: ENSG00000128609.16HGNC: HGNC:7688UniProt: A0A024R772
118PubMed Papers
20Diseases
3Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingrespiratory chain complex Imitochondrionmitochondrial inner membranetype 2 diabetes mellitusdiabetes mellitusneurodegenerative diseaseParkinson disease
✦AI Summary

NDUFA5 encodes a 13-kDa accessory subunit of mitochondrial respiratory complex I (NADH:ubiquinone oxidoreductase) that plays a crucial role in complex I assembly and function 1. The gene spans 14 kb on chromosome 7 and contains 5 exons 1. NDUFA5 is essential for the formation of the extramembrane arm of human mitochondrial complex I, specifically required for assembly and/or stability of the electron transferring Q module in the peripheral arm 2. The protein functions in mitochondrial electron transport from NADH to ubiquinone, contributing to ATP synthesis through proton motive force. NDUFA5 is subject to post-translational regulation, with acetylation of this subunit leading to reduced complex I activity 3. Disease associations include Parkinson's disease, where MPTP-induced acetylation of NDUFA5 contributes to mitochondrial dysfunction and dopaminergic neuronal death 3. The gene shows differential expression in cyanotic congenital heart disease 4 and serves as a potential biomarker for recurrent venous thromboembolism 5. Additionally, NDUFA5 variants have been associated with autism in Japanese populations 6, and the gene is targeted by miR-33a in hepatic steatosis 7.

Sources cited
1
NDUFA5 encodes a 13-kDa subunit and gene structure/chromosomal location
PMID: 10343126
2
NDUFA5 is required for complex I extramembrane arm formation and Q module assembly/stability
PMID: 24717771
3
NDUFA5 acetylation reduces complex I activity in Parkinson's disease models
PMID: 40597361
4
NDUFA5 is differentially expressed in cyanotic congenital heart disease
PMID: 40651188
5
NDUFA5 as potential biomarker for recurrent venous thromboembolism
PMID: 26397997
6
NDUFA5 variants associated with autism in Japanese population
PMID: 20825370
7
NDUFA5 is targeted by miR-33a in hepatic steatosis
PMID: 30324697
Disease Associationsⓘ20
type 2 diabetes mellitusOpen Targets
0.62Moderate
diabetes mellitusOpen Targets
0.61Moderate
neurodegenerative diseaseOpen Targets
0.55Moderate
Parkinson diseaseOpen Targets
0.54Moderate
multiple sclerosisOpen Targets
0.49Moderate
Alzheimer diseaseOpen Targets
0.47Moderate
lysosomal storage diseaseOpen Targets
0.46Moderate
polycystic ovary syndromeOpen Targets
0.41Moderate
gestational diabetesOpen Targets
0.41Moderate
Insulin resistanceOpen Targets
0.40Moderate
obesityOpen Targets
0.40Weak
prediabetes syndromeOpen Targets
0.40Weak
metabolic syndromeOpen Targets
0.39Weak
type 1 diabetes mellitusOpen Targets
0.39Weak
Disorder of lipid metabolismOpen Targets
0.38Weak
agingOpen Targets
0.37Weak
prostate cancerOpen Targets
0.36Weak
COVID-19Open Targets
0.36Weak
abnormal glucose toleranceOpen Targets
0.36Weak
metabolic diseaseOpen Targets
0.35Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
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
ATP5MEProtein interaction100%ATP5PFProtein interaction100%BLVRBProtein interaction100%COX5BProtein interaction100%COX6A2Protein interaction100%COX6B1Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
63%
Bone Marrow
27%
Liver
25%
Ovary
15%
Lung
12%
Gene Interaction Network
Click a node to explore
NDUFA5ATP5MEATP5PFBLVRBCOX5BCOX6A2COX6B1
PROTEIN STRUCTURE
Preparing viewer…
PDB5XTB · 3.40 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.41LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.78 [0.46–1.41]
RankingsWhere NDUFA5 stands among ~20K protein-coding genes
  • #4,004of 20,598
    Most Researched118 · top quartile
  • #588of 1,025
    FDA-Approved Drug Targets2
  • #14,553of 17,882
    Most Constrained (LOEUF)1.41
Genes detectedNDUFA5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Supernumerary subunits NDUFA3, NDUFA5 and NDUFA12 are required for the formation of the extramembrane arm of human mitochondrial complex I.
PMID: 24717771
FEBS Lett · 2014
1.00
2
Genomic organization of the human complex I 13-kDa subunit gene NDUFA5.
PMID: 10343126
Cytogenet Cell Genet · 1999
0.90
3
Deficient AMPK-SENP1-Sirt3 signaling impairs mitochondrial complex I function in Parkinson's disease model.
PMID: 40597361
Transl Neurodegener · 2025
0.80
4
Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic review.
PMID: 40651188
EBioMedicine · 2025
0.70
5
The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism.
PMID: 20825370
Acta Psychiatr Scand · 2011
0.60