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CPOX gene

coproporphyrinogen oxidase

Normal Function

The CPOX gene provides instructions for making an enzyme known as coproporphyrinogen oxidase. This enzyme is involved in the production of a molecule called heme. Heme is vital for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver. Heme is an essential component of iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).

The production of heme is a multi-step process that requires eight different enzymes. Coproporphyrinogen oxidase is responsible for the sixth step in this process, the removal of carbon and oxygen atoms from coproporphyrinogen III (the product of the fifth step) to form protoporphyrinogen IX. In subsequent steps, two other enzymes modify protoporphyrinogen IX and incorporate an iron atom to produce heme.

Health Conditions Related to Genetic Changes


At least 45 mutations in the CPOX gene have been found to cause porphyria. Mutations in this gene can cause two types of porphyria: hereditary coproporphyria and a variant known as harderoporphyria.

Most CPOX gene mutations change single protein building blocks (amino acids) in coproporphyrinogen oxidase. A single mutation appears to be responsible for harderoporphyria; this genetic change replaces the amino acid glycine with the amino acid glutamic acid at position 404 (written as Lys404Glu or K404E). Mutations in the CPOX gene reduce the activity of coproporphyrinogen oxidase, allowing compounds called porphyrins to build up in the body. These compounds are formed during the normal process of heme production, but reduced activity of coproporphyrinogen oxidase allows them to accumulate to toxic levels. This buildup, in combination with nongenetic factors such as certain drugs, alcohol, and dieting, leads to the signs and symptoms of hereditary coproporphyria and harderoporphyria.

More About This Health Condition

Other Names for This Gene

  • Coprogen oxidase
  • Coproporphyrinogen III oxidase, mitochondrial
  • Coproporphyrinogen III Oxidases
  • coproporphyrinogen oxidase (coproporphyria, harderoporphyria)
  • Coproporphyrinogen:oxygen oxidoreductase (decarboxylating)
  • Coproporphyrinogenase
  • COX
  • CPO
  • CPX
  • HCP

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases


  • Badminton MN, Elder GH. Molecular mechanisms of dominant expression in porphyria. J Inherit Metab Dis. 2005;28(3):277-86. doi: 10.1007/s10545-005-8050-3. Citation on PubMed
  • Elder GH. Genetic defects in the porphyrias: types and significance. Clin Dermatol. 1998 Mar-Apr;16(2):225-33. doi: 10.1016/s0738-081x(97)00202-2. No abstract available. Citation on PubMed
  • Gouya L, Puy H, Robreau AM, Lyoumi S, Lamoril J, Da Silva V, Grandchamp B, Deybach JC. Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias. Hum Genet. 2004 Feb;114(3):256-62. doi: 10.1007/s00439-003-1059-5. Epub 2003 Dec 11. Citation on PubMed
  • Kauppinen R. Porphyrias. Lancet. 2005 Jan 15-21;365(9455):241-52. doi: 10.1016/S0140-6736(05)17744-7. Citation on PubMed
  • Lamoril J, Puy H, Whatley SD, Martin C, Woolf JR, Da Silva V, Deybach JC, Elder GH. Characterization of mutations in the CPO gene in British patients demonstrates absence of genotype-phenotype correlation and identifies relationship between hereditary coproporphyria and harderoporphyria. Am J Hum Genet. 2001 May;68(5):1130-8. doi: 10.1086/320118. Epub 2001 Apr 16. Citation on PubMed or Free article on PubMed Central
  • Lee DS, Flachsova E, Bodnarova M, Demeler B, Martasek P, Raman CS. Structural basis of hereditary coproporphyria. Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14232-7. doi: 10.1073/pnas.0506557102. Epub 2005 Sep 21. Citation on PubMed or Free article on PubMed Central
  • Rosipal R, Lamoril J, Puy H, Da Silva V, Gouya L, De Rooij FW, Te Velde K, Nordmann Y, Martasek P, Deybach JC. Systematic analysis of coproporphyrinogen oxidase gene defects in hereditary coproporphyria and mutation update. Hum Mutat. 1999;13(1):44-53. doi: 10.1002/(SICI)1098-1004(1999)13:13.0.CO;2-Q. Citation on PubMed
  • Sassa S, Kappas A. Molecular aspects of the inherited porphyrias. J Intern Med. 2000 Feb;247(2):169-78. doi: 10.1046/j.1365-2796.2000.00618.x. Citation on PubMed
  • Schmitt C, Gouya L, Malonova E, Lamoril J, Camadro JM, Flamme M, Rose C, Lyoumi S, Da Silva V, Boileau C, Grandchamp B, Beaumont C, Deybach JC, Puy H. Mutations in human CPO gene predict clinical expression of either hepatic hereditary coproporphyria or erythropoietic harderoporphyria. Hum Mol Genet. 2005 Oct 15;14(20):3089-98. doi: 10.1093/hmg/ddi342. Epub 2005 Sep 13. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.