NDUFA6

Chr 22AR

NADH:ubiquinone oxidoreductase subunit A6

Also known as: B14, CI-B14, LYRM6, MC1DN33, NADHB14

NCBI Gene: 4700ENSG00000184983UniProt: P56556

This gene encodes a member of the LYR family of proteins that contain a highly conserved tripeptide (LYR) motif near the N-terminus. The encoded protein is an accessory subunit of NADH: ubiquinone oxidorerductase (Complex I), which is the largest enzyme of the mitochondrial membrane respiratory chain. Complex I functions in electron transfer from NADH to the respiratory chain. [provided by RefSeq, Oct 2016]

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 33MIM #618253
AR
122
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NDUFA6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
122 total variants — no pathogenic classifications of 122 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.
1.71LOEUF
pLI 0.000
Z-score 0.17
OE 0.93 (0.50–1.71)
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.
-0.80Z-score
OE missense 1.24 (1.06–1.45)
111 obs / 89.7 exp
Tolerant

Tolerant to missense variation

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.0.93 (0.50–1.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.24 (1.06–1.45)
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.1.60
0≤1.21.6
LoF obs/exp: 6 / 6.5Missense obs/exp: 111 / 89.7Syn Z: -2.70

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

NDUFA6 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NDUFA6-related early onset isolated mitochondrial complex I deficiency

strong
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 33

MIM #618253

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Ceramide(d18:1/18:1)-NDUFA6 interaction inactivates respiratory complex I to attenuate oxidative-stress-driven pathogenesis in liver ischemia/reperfusion injury.
Wang K et al.·JCI Insight
2025
A missense variant in NDUFA6 confers schizophrenia risk by affecting YY1 binding and NAGA expression.
Li Y et al.·Mol Psychiatry
2021
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
LncRNA NDUFA6-DT: A Comprehensive Analysis of a Potential LncRNA Biomarker and Its Regulatory Mechanisms in Gliomas.
Huang R et al.·Genes (Basel)
2024Functional
An Overview of Drug-Resistant Epilepsies Based on Advances in Genetics: A Cohort Study.
Kılıç B et al.·Neurol India
2026Review
Identification of N6-Methyladenosine-Associated lncRNAs and Analysis of Prognostic Signature in Breast Cancer.
Gu Y et al.·Biochem Genet
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Ndufa6 regulates adipogenic differentiation via Scd1.
Zhang J et al.·Adipocyte
2021🔓 Open Access
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