NDUFA12

Chr 12AR

NADH:ubiquinone oxidoreductase subunit A12

NCBI Gene: 55967ENSG00000184752UniProt: Q9UI09

Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 23MIM #618244
AR
115
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NDUFA12
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 46 VUS of 115 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.49LOEUF
pLI 0.000
Z-score 0.54
OE 0.80 (0.46–1.49)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.00Z-score
OE missense 1.00 (0.84–1.20)
83 obs / 83.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.80 (0.46–1.49)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.84–1.20)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 7 / 8.7Missense obs/exp: 83 / 83.1Syn Z: -0.92

ClinVar Variant Classifications

115 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic6
VUS46
Likely Benign37
Benign12
Conflicting1
13
Pathogenic
6
Likely Pathogenic
46
VUS
37
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
8
0
13
Likely Pathogenic
2
1
3
0
6
VUS
4
36
5
1
46
Likely Benign
0
3
18
16
37
Benign
0
0
11
1
12
Conflicting
—1
Total10414518115

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NDUFA12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NDUFA12-related mitochondrial complex I deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex I deficiency, nuclear type 23

MIM #618244

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — NDUFA12
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel NDUFA12 variants are associated with isolated complex I defect and variable clinical manifestation.
Torraco A et al.·Hum Mutat
2021Case report
Dysregulated immune and metabolic pathways are associated with poor survival in adult acute myeloid leukemia with CEBPA bZIP in-frame mutations.
Tien FM et al.·Blood Cancer J
2024
Sex-stratified genome-wide meta-analysis identifies novel loci for cognitive decline in older adults.
Acharya V et al.·Alzheimers Dement
2025Meta-analysis
Autosomal recessive Leber hereditary optic neuropathy, a new neuro-ophthalmo-genetic paradigm.
Lenaers G et al.·Brain
2023
Enhanced Anticancer Activity of 7MeERT over Ertredin: A Comparative Study on Cancer Cell Proliferation and NDUFA12 Binding.
Atsumi S et al.·Biomolecules
2024
Bi-allelic Mutations in NDUFA6 Establish Its Role in Early-Onset Isolated Mitochondrial Complex I Deficiency.
Alston CL et al.·Am J Hum Genet
2018
A Homozygous NDUFS6 Variant Associated with Neuropathy and Optic Atrophy.
Gangfuß A et al.·J Neuromuscul Dis
2024Case report
Meta single-cell atlas and xQTL post-GWAS analysis revealed the pathogenic features of thyroid cancer for target therapy: A multi-omics study.
Zhang C et al.·Cancer Gene Ther
2026
Data mining of high density genomic variant data for prediction of Alzheimer's disease risk.
Briones N et al.·BMC Med Genet
2012
Single-Cell RNA Sequencing and Network Pharmacology Reveal the Potential Role of Oxidative Phosphorylation Inactivation in Diagnosing and Treating Chronic Tendon Injuries.
Niu JJ et al.·J Gene Med
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
An Immune Cell Activation Signature for Non - Small Cell Lung Cancer Revealed Tumor Microenvironment Heterogeneity and the Role of RORA in Regulating ZNF490/NDUFA12 Axis.
Song Y et al.·Curr Med Chem
2026
Identifying NDUFA12 mutation in a Saudi family: An unusual presentation of mitochondrial Complex I deficiency mimicking as idiopathic intracranial hypertension in a patient with papilledema and visual loss.
Alshamrani FJ et al.·J Family Community Med
2026🔓 Open Access
When the Expected Scenario Did Not Occur: A Novel NDUFA12 Mutation Resembling Neuromyelitis Optica Spectrum Disorder.
Koçak A et al.·J Child Neurol
2025
NDUFA12 as a Functional Target of the Anticancer Compound Ertredin in Human Hepatoma Cells As Revealed by Label-Free Chemical Proteomics.
Park SI et al.·J Proteome Res
2024Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools