COX10

Chr 17AR

cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10

Also known as: MC4DN3

NCBI Gene: 1352 ENSG00000006695 UniProt: Q12887 OMIM: 602125

The protein encodes heme A:farnesyltransferase, which is essential for the maturation of the heme A prosthetic group required for functional cytochrome c oxidase (complex IV) assembly. Biallelic mutations cause mitochondrial complex IV deficiency, nuclear type 3, inherited in an autosomal recessive pattern. The disease predominantly results from loss-of-function mutations that impair the enzyme's ability to process heme A, leading to defective complex IV assembly and mitochondrial respiratory chain dysfunction.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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 heme A:farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. This protein is predicted to contain 7-9 transmembrane domains localized in the mitochondrial inner membrane. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 3MIM #619046

Clinical highlights

Gene-disease validity (ClinGen)

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

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.61

LOEUF

Mechanism· predicted

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GeneReview available — COX10

Authoritative clinical overview · Recommended first read