COX15

Chr 10AR

cytochrome c oxidase assembly factor COX15

Also known as: CEMCOX2, HAS, MC4DN6

NCBI Gene: 1355 ENSG00000014919 UniProt: Q7KZN9 OMIM: 603646

The protein functions in the biogenesis of cytochrome c oxidase (complex IV) and is involved in the hydroxylation of heme O, which is essential for proper assembly of this terminal component of the mitochondrial respiratory chain. Mutations cause mitochondrial complex IV deficiency through an autosomal recessive inheritance pattern, resulting in impaired cellular respiration. The pathogenic mechanism involves loss of function leading to defective complex IV assembly and subsequent mitochondrial dysfunction.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes a protein which is not a structural subunit, but may be essential for the biogenesis of COX formation and may function in the hydroxylation of heme O, according to the yeast mutant studies. This protein is predicted to contain 5 transmembrane domains localized in the mitochondrial inner membrane. Alternative splicing of this gene generates two transcript variants diverging in the 3' region. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 6MIM #615119

Clinical highlights

Gene-disease validity (ClinGen)

mitochondrial disease · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.33

LOEUF

LOF

Mechanism· G2P

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GeneReview available — COX15