NDUFA9

Chr 12AR

NADH:ubiquinone oxidoreductase subunit A9

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

NCBI Gene: 4704 ENSG00000139180 UniProt: Q16795 OMIM: 603834

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex I), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane. A pseudogene has been identified on chromosome 12. [provided by RefSeq, May 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 26MIM #618247

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

Mechanism· predicted

📖

GeneReview available — NDUFA9

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.005

Z-score 2.84

OE 0.35 (0.21–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.88–1.10)

226 obs / 229.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.21–0.64)

0≤0.351.4

Missense OE?0.98 (0.88–1.10)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 8 / 22.6Missense obs/exp: 226 / 229.7Syn Z: -0.28

Background carrier burden — how many people carry a rare variant somewhere in NDUFA9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

589 rare PASS variants

Rare truncating (LoF)

1 in 1,300

61 rare PASS variants

Rare synonymous (reference)

1 in 160

230 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NDUFA9. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 1,100
South Asian	~43k	1 in 80	1 in 3,900
Remaining (unassigned)	~30k	1 in 58	1 in 1,300
European (Finnish)	~27k	1 in 370	≈ 1 in 9,600
Admixed American	~22k	1 in 69	1 in 1,300
African / African American	~21k	1 in 120	1 in 1,100
East Asian	~20k	1 in 62	1 in 1,700
Ashkenazi Jewish	~13k	1 in 1,200	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 90	≈ 1 in 810

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓