COXFA4

Chr 7AR

cytochrome c oxidase associated subunit FA4

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

NCBI Gene: 4697 ENSG00000189043 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.

GeneReviews 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]

GeneReviews OMIM ResearchGenerating clinical summary…

AR1 OMIM phenotype

Clinical Summary— COXFA4

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 11 VUS of 46 total submissions

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GeneReview available — COXFA4

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

gnomad: Error: Gene not found

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic2

VUS11

Likely Benign21

Benign2

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	0	0	0	3
Likely Pathogenic	2	0	0	0	2
VUS	1	10	0	0	11
Likely Benign	0	0	15	6	21
Benign	0	0	2	0	2
Conflicting	—				1
Total	6	10	17	6	40

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap COXFA4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →