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.

Summary from RefSeq, OMIM, UniProt, Mechanism
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Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 26MIM #618247
AR
0
Active trials
10
Pubs (1 yr)
69
P/LP submissions
7%
P/LP missense
0.64
LOEUF
DN
Mechanism· predicted
Clinical SummaryNDUFA9
🧬
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.
📋
ClinVar Variants
69 unique Pathogenic / Likely Pathogenic· 138 VUS of 350 total submissions
📖
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

350 submitted variants in ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic10
VUS138
Likely Benign74
Benign41
Conflicting11
59
Pathogenic
10
Likely Pathogenic
138
VUS
74
Likely Benign
41
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
5
54
0
59
Likely Pathogenic
2
0
8
0
10
VUS
3
119
15
1
138
Likely Benign
0
8
29
37
74
Benign
0
3
37
1
41
Conflicting
11
Total513514339333

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

View 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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