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COXFA4

Chr 7AR

cytochrome c oxidase associated subunit FA4

Also known as: CI-9k, CI-MLRQ, MC4DN21, MISTR1, MLRQ, MRCAF1, NDUFA4

NCBI Gene: 4697 UniProt: O00483 OMIM: 603833

COXFA4 encodes a component of cytochrome c oxidase (complex IV) that is required for complex IV maintenance and catalyzes the reduction of oxygen to water in the mitochondrial electron transport chain. Mutations cause mitochondrial complex IV deficiency, nuclear type 21, which is inherited in an autosomal recessive pattern. This condition affects the mitochondrial respiratory chain and energy production in cells.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the complex I 9kDa subunit family. Mammalian complex I of mitochondrial respiratory chain is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 21MIM #619065

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (2)

ensembl: Error: Ensembl fetch failed: 400 for /lookup/symbol/homo_sapiens/COXFA4?content-type=application/json

gnomad: Error: Gene not found

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in COXFA4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 920

116 rare PASS variants

Rare truncating (LoF)

1 in 5,100

22 rare PASS variants

Rare synonymous (reference)

1 in 2,200

44 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COXFA4. 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 1,200	1 in 4,000
South Asian	~43k	1 in 440	1 in 6,200
Remaining (unassigned)	~30k	1 in 600	≈ 1 in 15,000
European (Finnish)	~27k	≈ 1 in 8,900	none seen
Admixed American	~22k	1 in 830	none seen
African / African American	~21k	1 in 400	≈ 1 in 17,000
East Asian	~20k	1 in 960	≈ 1 in 20,000
Ashkenazi Jewish	~13k	none seen	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 570	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.