NDUFB9

Chr 8

NADH:ubiquinone oxidoreductase subunit B9

Also known as: B22, CI-B22, LYRM3, MC1DN24, UQOR22

NCBI Gene: 4715 ENSG00000147684 UniProt: Q9Y6M9

The protein is an accessory subunit of mitochondrial complex I (NADH dehydrogenase) that functions in electron transfer from NADH to ubiquinone in the respiratory chain. Mutations cause mitochondrial complex I deficiency with autosomal recessive inheritance, though the specific clinical phenotype associated with NDUFB9 mutations remains uncertain. Complex I deficiencies typically present with variable manifestations including neonatal disease, cardiomyopathy, liver disease, and neurodegenerative disorders.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a subunit of the mitochondrial oxidative phosphorylation complex I (nicotinamide adenine dinucleotide: ubiquinone oxidoreductase). Complex I is localized to the inner mitochondrial membrane and functions to dehydrogenate nicotinamide adenine dinucleotide and to shuttle electrons to coenzyme Q. Complex I deficiency is the most common defect found in oxidative phosphorylation disorders and results in a range of conditions, including lethal neonatal disease, hypertrophic cardiomyopathy, liver disease, and adult-onset neurodegenerative disorders. Pseudogenes of this gene are found on chromosomes five, seven and eight. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMitochondrial complex I deficiency, nuclear type 24

Clinical highlights

Gene–disease validity (ClinGen)

Limited · mitochondrial disease · AR · ClinGen 2024

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.04

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.45

OE 0.58 (0.34–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.00Z-score

OE missense 1.00 (0.85–1.18)

104 obs / 104.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.34–1.04)

0≤0.351.4

Missense OE?1.00 (0.85–1.18)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 8 / 13.8Missense obs/exp: 104 / 104.0Syn Z: 0.10

Background carrier burden — how many people carry a rare variant somewhere in NDUFB9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

285 rare PASS variants

Rare truncating (LoF)

1 in 670

57 rare PASS variants

Rare synonymous (reference)

1 in 450

103 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NDUFB9. 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 150	1 in 860
South Asian	~43k	1 in 140	1 in 3,900
Remaining (unassigned)	~30k	1 in 90	1 in 880
European (Finnish)	~27k	1 in 880	1 in 3,300
Admixed American	~22k	1 in 140	1 in 3,700
African / African American	~21k	1 in 160	1 in 1,200
East Asian	~20k	1 in 190	1 in 1,200
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,884	1 in 140	none seen

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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓