COX4I1

Chr 16AR

cytochrome c oxidase subunit 4I1

Also known as: COX IV-1, COX4, COX4-1, COXIV, COXIV-1, MC4DN16

NCBI Gene: 1327 ENSG00000131143 UniProt: P13073 OMIM: 123864

COX4I1 encodes subunit IV isoform 1 of cytochrome c oxidase (complex IV), the terminal enzyme of the mitochondrial electron transport chain that reduces oxygen to water and contributes to ATP production through oxidative phosphorylation. Mutations cause mitochondrial complex IV deficiency, nuclear type 16, which follows autosomal recessive inheritance. This gene has a relatively low constraint against loss-of-function variants (pLI 0.39, LOEUF 0.68), suggesting some tolerance to heterozygous loss of function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane. The complex consists of 13 mitochondrial- and nuclear-encoded subunits. The mitochondrially-encoded subunits perform the electron transfer and proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex. This gene encodes the nuclear-encoded subunit IV isoform 1 of the human mitochondrial respiratory chain enzyme. It is located at the 3' of the NOC4 (neighbor of COX4) gene in a head-to-head orientation, and shares a promoter with it. Pseudogenes related to this gene are located on chromosomes 13 and 14. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex IV deficiency, nuclear type 16MIM #619060

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARLimitednot for standalone diagnostic reporting2 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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

Mechanism· predicted

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GeneReview available — COX4I1

Authoritative clinical overview · Recommended first read