NDUFA9

Chr 12AR

NADH:ubiquinone oxidoreductase subunit A9

Also known as: CC6, CI-39k, CI39k, COQ11, MC1DN26, NDUFS2L, SDR22E1

The protein is a subunit of NADH:ubiquinone oxidoreductase (complex I), the first enzyme complex in the mitochondrial electron transport chain. Mutations cause mitochondrial complex I deficiency, nuclear type 26, inherited in an autosomal recessive pattern. The pathogenic mechanism appears to involve dominant-negative effects.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.641 OMIM phenotype
Clinical SummaryNDUFA9
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📖
GeneReview available — NDUFA9
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.005
Z-score 2.84
OE 0.35 (0.210.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.09Z-score
OE missense 0.98 (0.881.10)
226 obs / 229.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.210.64)
00.351.4
Missense OE0.98 (0.881.10)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 8 / 22.6Missense obs/exp: 226 / 229.7Syn Z: -0.28
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedNDUFA9-related Leigh syndromeOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7131th %ile
GOF
0.5660th %ile
LOF
0.3357th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NDUFA9 · 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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