- Human pathology

Home > A. Molecular pathology > COX


Monday 6 October 2003

The cytochrome c oxidase (COX) are the terminal enzymes in the respiratory chain. Cytochrome c oxidase catalyzes the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane.

Mitochondrial DNA encodes 3 COX subunits, I-III (MIM.516030), and nuclear DNA encodes 10 (MIM.123870).


3 mitochondrial COX genes (COX1, COX2, COX3), one mitochondrial tRNA(ser) (MTTS1) (MIM.590080)

mitochondrial COX genes COX1 COX2 COX3 COX4
nuclear COX genes COX5 COX6 COX7 COX8 COX9 COX10
nuclear COX genes COX11 COX12 COX13 COX14 COX15


Deficiencies in the activity of cytochrome c oxidases, COXs deficiency, mitochondrial respiratory chain complex IV deficiency (MIM.220110)

- COX10 (mutations in progressive mitochondrial encephalopathy with proximal renal tubulopathy due to cytochrome C oxidase deficiency) (MIM.602125)

- COX15 (mutations in early-onset fatal hypertrophic cardiomyopathy)

- SCO1 (17p12-12) (mutations in early-onset hepatic failure with neurologic disorder) (MIM.603644)

- SCO2 (22q13) (fatal infantile cardioencephalomyopathy due to cytochrome C oxydase deficiency (MIM.604272)

- frequent cause of autosomal recessive mitochondrial disease in infants.

- COX15 mutations in fatal infantile hypertrophic cardiomyopathy

- SCO2 mutations in fatal infantile cardioencephalomyopathy (MIM.604377)


- Barrientos A, Barros MH, Valnot I, Rotig A, Rustin P, Tzagoloff A. Cytochrome oxidase in health and disease.
Gene. 2002 Mar 6;286(1):53-63. PMID: 11943460

- Shoubridge EA. Nuclear genetic defects of oxidative phosphorylation. Hum Mol Genet. 2001 Oct 1;10(20):2277-84. PMID: 11673411

- Smeitink J, van den Heuvel L, DiMauro S. The genetics and pathology of oxidative phosphorylation. Nat Rev Genet. 2001 May;2(5):342-52. PMID: 11331900