NDUFA11

Chr 19AR

NADH:ubiquinone oxidoreductase subunit A11

Also known as: B14.7, CI-B14.7, MC1DN14

The protein is a subunit of mitochondrial complex I that functions as the NADH-ubiquinol reductase in the electron transport chain. Mutations cause mitochondrial complex I deficiency, nuclear type 14, inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects where mutant protein disrupts normal complex I assembly or function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 1.541 OMIM phenotype
Clinical SummaryNDUFA11
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.54LOEUF
pLI 0.018
Z-score 0.77
OE 0.62 (0.281.54)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.54Z-score
OE missense 0.87 (0.751.01)
117 obs / 134.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.281.54)
00.351.4
Missense OE0.87 (0.751.01)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 3 / 4.8Missense obs/exp: 117 / 134.7Syn Z: 0.52
DN
0.79top 25%
GOF
0.6540th %ile
LOF
0.3357th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NDUFA11 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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