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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NDUFA9
NADH:ubiquinone oxidoreductase subunit A9
Chromosome 12 Β· 12p13.32
NCBI Gene: 4704Ensembl: ENSG00000139180.12HGNC: HGNC:7693UniProt: Q16795
138PubMed Papers
21Diseases
3Drugs
11Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrionmitochondrial inner membranenucleusmitochondrial matrixmitochondrial complex I deficiency, nuclear type 26type 2 diabetes mellitusdiabetes mellitusmitochondrial complex I deficiency
✦AI Summary

NDUFA9 is an accessory subunit of mitochondrial respiratory chain Complex I (NADH:ubiquinone oxidoreductase) that plays a critical structural rather than catalytic role 1. NDUFA9 is essential for stabilizing the junction between the membrane and matrix arms of Complex I, a late assembly step required for proper Complex I biogenesis 1. Loss of functional NDUFA9 results in impaired Complex I assembly, accumulation of membrane arm subcomplexes lacking matrix arm markers, and cell growth defects under oxidative phosphorylation-dependent conditions 1. NDUFA9 mutations cause Mitochondrial Complex I Deficiency, Nuclear Type 26, reflecting its essential role in oxidative metabolism. The gene's expression is dysregulated in several disease contexts: it serves as a diagnostic biomarker in sepsis-induced myocardial dysfunction 2, is targeted by miR-34a-5p in Huntington's disease pathomechanisms 3, and is involved in the LINC01133-hsa-miR-4726-5p-NDUFA9 axis mediating astrocytic dysfunction from HIV and cocaine coexposure 4. NDUFA9 expression is also altered in idiopathic pulmonary fibrosis and pemphigus vulgaris, implicating oxidative phosphorylation dysfunction in these pathologies 56. These findings suggest NDUFA9 represents a convergence point for multiple disease mechanisms involving mitochondrial bioenergetics.

Sources cited
1
NDUFA9 is essential for stabilizing the junction between membrane and matrix arms of Complex I and is required for proper Complex I assembly and activity
PMID: 23223238
2
NDUFA9 is identified as a diagnostic gene in sepsis-induced myocardial dysfunction through machine learning analysis
PMID: 40165133
3
NDUFA9 is a direct target gene of miR-34a-5p in Huntington's disease pathomechanisms
PMID: 37013480
4
NDUFA9 is involved in the LINC01133-hsa-miR-4726-5p-NDUFA9 axis regulating astrocytic energy metabolism in HIV and cocaine coexposure
PMID: 35892093
5
NDUFA9 is identified as a key oxidative stress-related gene in idiopathic pulmonary fibrosis pathogenesis through multi-omics analysis
PMID: 40592928
6
NDUFA9 is highly expressed in keratinocytes and involved in oxidative phosphorylation pathway activation in pemphigus vulgaris
PMID: 39373252
Disease Associationsβ“˜21
mitochondrial complex I deficiency, nuclear type 26Open Targets
0.66Moderate
type 2 diabetes mellitusOpen Targets
0.61Moderate
diabetes mellitusOpen Targets
0.60Moderate
mitochondrial complex I deficiencyOpen Targets
0.59Moderate
Parkinson diseaseOpen Targets
0.58Moderate
neurodegenerative diseaseOpen Targets
0.58Moderate
multiple sclerosisOpen Targets
0.53Moderate
Leigh syndromeOpen Targets
0.53Moderate
Alzheimer diseaseOpen Targets
0.51Moderate
lysosomal storage diseaseOpen Targets
0.50Moderate
polycystic ovary syndromeOpen Targets
0.41Moderate
genetic disorderOpen 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
Mitochondrial complex I deficiency, nuclear type 26UniProt
Pathogenic Variants11
NM_005002.5(NDUFA9):c.897-1G>CLikely pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜…β˜†β˜†β˜†2025
NM_005002.5(NDUFA9):c.552+1_552+5delLikely pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜…β˜†β˜†β˜†2025
NM_005002.5(NDUFA9):c.895C>T (p.Arg299Ter)Pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜…β˜†β˜†β˜†2024β†’ Residue 299
NM_005002.5(NDUFA9):c.394C>T (p.Arg132Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2021β†’ Residue 132
NM_005002.5(NDUFA9):c.938G>A (p.Trp313Ter)Likely pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜…β˜†β˜†β˜†2019β†’ Residue 313
NM_005002.5(NDUFA9):c.267T>A (p.Tyr89Ter)Likely pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜…β˜†β˜†β˜†β†’ Residue 89
NM_005002.5(NDUFA9):c.710A>T (p.Lys237Ile)Pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜†β˜†β˜†β˜†2026β†’ Residue 237
NM_005002.5(NDUFA9):c.1069C>G (p.Arg357Gly)Pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜†β˜†β˜†β˜†2026β†’ Residue 357
NM_005002.5(NDUFA9):c.800G>T (p.Gly267Val)Pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜†β˜†β˜†β˜†2026β†’ Residue 267
NM_005002.5(NDUFA9):c.1078C>G (p.Arg360Gly)Pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜†β˜†β˜†β˜†2026β†’ Residue 360
NM_005002.5(NDUFA9):c.962G>C (p.Arg321Pro)Pathogenic
Mitochondrial complex I deficiency, nuclear type 26
β˜†β˜†β˜†β˜†2012β†’ Residue 321
View on ClinVar β†—
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
COX5BProtein interaction100%COX6A2Protein interaction100%COX7A1Protein interaction100%ND1Protein interaction100%ND2Protein interaction100%ND3Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
99%
Liver
61%
Lung
35%
Bone Marrow
29%
Ovary
27%
Gene Interaction Network
Click a node to explore
NDUFA9COX5BCOX6A2COX7A1ND1ND2ND3
PROTEIN STRUCTURE
Preparing viewer…
PDB5XTB Β· 3.40 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.78LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.53 [0.36–0.78]
RankingsWhere NDUFA9 stands among ~20K protein-coding genes
  • #3,345of 20,598
    Most Researched138 Β· top quartile
  • #580of 1,025
    FDA-Approved Drug Targets2
  • #2,746of 5,498
    Most Pathogenic Variants11
  • #6,417of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedNDUFA9
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Autophagy deficiency abolishes liver mitochondrial DNA segregation.
PMID: 35220898
Autophagy Β· 2022
1.00
2
The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.
PMID: 22682224
Cell Metab Β· 2012
0.90
3
Gene knockout using transcription activator-like effector nucleases (TALENs) reveals that human NDUFA9 protein is essential for stabilizing the junction between membrane and matrix arms of complex I.
PMID: 23223238
J Biol Chem Β· 2013
0.80
4
Integrated bioinformatics and experiment validation reveal cuproptosis-related biomarkers and therapeutic targets in sepsis-induced myocardial dysfunction.
PMID: 40165133
BMC Infect Dis Β· 2025
0.70
5
HIV-1 Tat and cocaine impact astrocytic energy reservoirs and epigenetic regulation by influencing the LINC01133-hsa-miR-4726-5p-NDUFA9 axis.
PMID: 35892093
Mol Ther Nucleic Acids Β· 2022
0.60