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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NDUFA12
NADH:ubiquinone oxidoreductase subunit A12
Chromosome 12 Β· 12q22
NCBI Gene: 55967Ensembl: ENSG00000184752.15HGNC: HGNC:23987UniProt: Q9UI09
70PubMed Papers
21Diseases
3Drugs
14Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingmitochondrial inner membranemitochondrionmitochondrial ATP synthesis coupled electron transportmitochondrial complex I deficiency, nuclear type 23mitochondrial complex I deficiencytype 2 diabetes mellitusdiabetes mellitus
✦AI Summary

NDUFA12 is an accessory subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), essential for electron transfer from NADH to the respiratory chain 1. Unlike core catalytic subunits, NDUFA12 is required for assembly and stability of the electron-transferring Q module in Complex I's peripheral arm, rather than direct catalysis 1. Biallelic loss-of-function NDUFA12 variants cause mitochondrial Complex I deficiency with substantial phenotypic heterogeneity 23. Clinical presentations range from severe Leigh syndrome with basal ganglia abnormalities to isolated optic atrophy, with disease onset and progression varying even among patients carrying identical variants 234. NDUFA12 defects represent an underappreciated cause of inherited optic neuropathies, including autosomal recessive Leber Hereditary Optic Neuropathy 4. Beyond mitochondrial disease, NDUFA12 has emerged as a therapeutic target in cancer biology. The compound Ertredin and its analogue 7MeERT inhibit cancer cell proliferation through NDUFA12 binding, suppressing oxidative phosphorylation and reducing oxygen consumption 56. Additionally, variants near NDUFA12 were associated with age-related executive function decline in females in genome-wide studies 7, and NDUFA12 was identified among obesity-associated genes in adipose tissue expression studies 8.

Sources cited
1
NDUFA12 is a supernumerary subunit required for formation and stability of the electron-transferring Q module in Complex I's peripheral arm
PMID: 24717771
2
Novel NDUFA12 variants cause Complex I deficiency with variable clinical manifestations, including Leigh syndrome, despite absence of NDUFA12 protein
PMID: 33715266
3
Biallelic NDUFA12 truncating variants cause mitochondrial disease with heterogeneous phenotypes ranging from dystonia/spasticity to isolated optic atrophy
PMID: 35141356
4
NDUFA12 defects are an underrated cause of inherited optic atrophy and autosomal recessive Leber Hereditary Optic Neuropathy
PMID: 41234160
5
NDUFA12 variants are associated with decline in executive function in older females in sex-stratified genome-wide analysis
PMID: 40042063
6
NDUFA12 was identified as an obesity-associated gene in meta-analysis of adipose tissue gene expression
PMID: 35063573
7
NDUFA12 is a functional target of the anticancer compound Ertredin, and its knockdown suppresses cancer cell proliferation
PMID: 38104258
8
7MeERT binds to NDUFA12, inhibits oxidative phosphorylation, and shows anticancer activity against multiple cancer cell types
PMID: 39334963
Disease Associationsβ“˜21
mitochondrial complex I deficiency, nuclear type 23Open Targets
0.75Strong
mitochondrial complex I deficiencyOpen Targets
0.63Moderate
type 2 diabetes mellitusOpen Targets
0.61Moderate
diabetes mellitusOpen Targets
0.60Moderate
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
mitochondrial diseaseOpen Targets
0.37Weak
prostate cancerOpen Targets
0.36Weak
COVID-19Open Targets
0.36Weak
abnormal glucose toleranceOpen Targets
0.36Weak
coronary artery diseaseOpen Targets
0.35Weak
metabolic diseaseOpen Targets
0.35Weak
Autosomal dominant polycystic kidney diseaseOpen Targets
0.34Weak
Mitochondrial complex I deficiency, nuclear type 23UniProt
Pathogenic Variants14
NM_018838.5(NDUFA12):c.69T>G (p.Tyr23Ter)Pathogenic
Mitochondrial complex I deficiency, nuclear type 23|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 23
NM_018838.5(NDUFA12):c.178C>T (p.Arg60Ter)Pathogenic
Mitochondrial complex I deficiency, nuclear type 23|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 60
NM_018838.5(NDUFA12):c.253G>T (p.Glu85Ter)Pathogenic
Mitochondrial complex I deficiency, nuclear type 23|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 85
NM_018838.5(NDUFA12):c.4G>T (p.Glu2Ter)Likely pathogenic
Mitochondrial complex I deficiency, nuclear type 23|SLC35A2-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 2
NM_018838.5(NDUFA12):c.168dup (p.Gly57fs)Likely pathogenic
Mitochondrial complex I deficiency, nuclear type 23
β˜…β˜†β˜†β˜†2025β†’ Residue 57
NM_018838.5(NDUFA12):c.5del (p.Glu2fs)Pathogenic
Mitochondrial complex I deficiency, nuclear type 23
β˜…β˜†β˜†β˜†2024β†’ Residue 2
NM_018838.5(NDUFA12):c.13C>T (p.Gln5Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 5
NM_018838.5(NDUFA12):c.169+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_018838.5(NDUFA12):c.61del (p.Arg21fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 21
NM_018838.5(NDUFA12):c.1A>G (p.Met1Val)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 1
NM_018838.5(NDUFA12):c.83del (p.Phe28fs)Pathogenic
Mitochondrial complex I deficiency, nuclear type 23
β˜†β˜†β˜†β˜†2022β†’ Residue 28
NM_018838.5(NDUFA12):c.224G>A (p.Trp75Ter)Pathogenic
Mitochondrial complex I deficiency, nuclear type 23
β˜†β˜†β˜†β˜†2021β†’ Residue 75
NM_018838.5(NDUFA12):c.86G>A (p.Arg29Lys)Pathogenic
Mitochondrial complex I deficiency, nuclear type 23
β˜†β˜†β˜†β˜†2021β†’ Residue 29
NM_018838.5(NDUFA12):c.395del (p.Lys132fs)Pathogenic
Mitochondrial complex I deficiency, nuclear type 23
β˜†β˜†β˜†β˜†2021β†’ Residue 132
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
ATP5F1CProtein interaction100%ATP5PBProtein interaction100%ATP5PFProtein interaction100%BLVRBProtein interaction100%COX4I1Protein interaction100%COX5BProtein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
66%
Liver
26%
Lung
24%
Bone Marrow
18%
Ovary
15%
Gene Interaction Network
Click a node to explore
NDUFA12ATP5F1CATP5PBATP5PFBLVRBCOX4I1COX5B
PROTEIN STRUCTURE
Preparing viewer…
PDB5XTB Β· 3.40 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.19LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.78 [0.53–1.19]
RankingsWhere NDUFA12 stands among ~20K protein-coding genes
  • #6,738of 20,598
    Most Researched70
  • #629of 1,025
    FDA-Approved Drug Targets2
  • #2,516of 5,498
    Most Pathogenic Variants14
  • #12,461of 17,882
    Most Constrained (LOEUF)1.19
Genes detectedNDUFA12
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Novel NDUFA12 variants are associated with isolated complex I defect and variable clinical manifestation.
PMID: 33715266
Hum Mutat Β· 2021
1.00
2
Supernumerary subunits NDUFA3, NDUFA5 and NDUFA12 are required for the formation of the extramembrane arm of human mitochondrial complex I.
PMID: 24717771
FEBS Lett Β· 2014
0.90
3
Recessive variants in mitochondrial Complex I nuclear subunits are an underrated cause of optic atrophy.
PMID: 41234160
Brain Β· 2025
0.80
4
Biallelic Loss-of-Function
PMID: 35141356
Mov Disord Clin Pract Β· 2022
0.70
5
Sex-stratified genome-wide meta-analysis identifies novel loci for cognitive decline in older adults.
PMID: 40042063
Alzheimers Dement Β· 2025
0.60