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Protoporphyrinogen oxidase
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols PPOX ; PPO; V290M; VP
External IDs OMIM600923 MGI104968 HomoloGene262 GeneCards: PPOX Gene
EC number
RNA expression pattern
PBB GE PPOX 204788 s at tn.png
More reference expression data
Species Human Mouse
Entrez 5498 19044
Ensembl ENSG00000143224 ENSMUSG00000062729
UniProt P50336 P51175
RefSeq (mRNA) NM_000309 NM_008911
RefSeq (protein) NP_000300 NP_032937
Location (UCSC) Chr 1:
161.14 – 161.15 Mb
Chr 1:
171.28 – 171.28 Mb
PubMed search [1] [2]

Protoporphyrinogen oxidase is an enzyme that in humans is encoded by the PPOX gene.[1][2][3]

This gene encodes the penultimate enzyme of heme biosynthesis, which catalyzes the 6-electron oxidation of protoporphyrinogen IX to form protoporphyrin IX. This protein is a flavoprotein associated with the outer surface of the inner mitochondrial membrane. Mutations in this gene cause variegate porphyria.[3]

PPOX (protoporphyrinogen oxidase) is a human gene that produces an enzyme called protoporphyrinogen oxidase. This enzyme is responsible for the seventh step in heme production. Heme is the portion of hemoglobin that carries oxygen in the blood from the lungs to the rest of the body. Each of the steps in heme production is controlled by a separate gene (see below). Protoporphyrinogen oxidase removes hydrogen atoms from protoporphyrinogen IX (the product of the sixth step in the production of heme) to form protoporphyrin IX. One additional enzyme must modify protoporphyrin IX before it becomes heme.

The PPOX gene is located on the long (q) arm of chromosome 1 at position 22, from base pair 157,949,266 to base pair 157,954,082.

The following genes are part of the chemical pathway for making heme.

  • ALAD: aminolevulinate, delta-, dehydratase
  • ALAS1: aminolevulinate, delta-, synthase 1
  • ALAS2: aminolevulinate, delta-, synthase 2 (sideroblastic/hypochromic anemia)
  • CPOX: coproporphyrinogen oxidase
  • FECH: ferrochelatase (protoporphyria)
  • HMBS: hydroxymethylbilane synthase
  • PPOX: protoporphyrinogen oxidase
  • UROD: uroporphyrinogen decarboxylase
  • UROS: uroporphyrinogen III synthase (congenital erythropoietic porphyria)

Related conditions[edit]

Variegate porphyria is caused by mutations in the PPOX gene. More than 100 mutations that can cause variegate porphyria have been identified in the PPOX gene. One mutation, a substitution of the amino acid tryptophan for arginine at position 59 (also written as Arg59Trp or R59W), is found in about 95 percent of South African families with variegate porphyria. Mutations in the PPOX gene reduce the activity of the enzyme made by the gene, allowing byproducts of heme production to build up in the body. This buildup, in combination with nongenetic factors (such as certain drugs, alcohol and dieting), causes this type of porphyria.


This article incorporates public domain text from The U.S. National Library of Medicine


  1. ^ Taketani S, Inazawa J, Abe T, Furukawa T, Kohno H, Tokunaga R, Nishimura K, Inokuchi H (Mar 1996). "The human protoporphyrinogen oxidase gene (PPOX): organization and location to chromosome 1". Genomics 29 (3): 698–703. doi:10.1006/geno.1995.9949. PMID 8575762. 
  2. ^ Frank J, McGrath JA, Poh-Fitzpatrick MB, Hawk JL, Christiano AM (Sep 1999). "Mutations in the translation initiation codon of the protoporphyrinogen oxidase gene underlie variegate porphyria". Clin Exp Dermatol 24 (4): 296–301. doi:10.1046/j.1365-2230.1999.00484.x. PMID 10457135. 
  3. ^ a b "Entrez Gene: PPOX protoporphyrinogen oxidase". 

Further reading[edit]

  • Nishimura K, Taketani S, Inokuchi H (1995). "Cloning of a human cDNA for protoporphyrinogen oxidase by complementation in vivo of a hemG mutant of Escherichia coli". J. Biol. Chem. 270 (14): 8076–80. doi:10.1074/jbc.270.14.8076. PMID 7713909. 
  • Dailey TA, Meissner P, Dailey HA (1994). "Expression of a cloned protoporphyrinogen oxidase". J. Biol. Chem. 269 (2): 813–5. PMID 8288631. 
  • Dailey TA, Dailey HA, Meissner P, Prasad AR (1996). "Cloning, sequence, and expression of mouse protoporphyrinogen oxidase". Arch. Biochem. Biophys. 324 (2): 379–84. doi:10.1006/abbi.1995.0051. PMID 8554330. 
  • Meissner PN; Dailey TA; Hift RJ et al. (1996). "A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria". Nat. Genet. 13 (1): 95–7. doi:10.1038/ng0596-95. PMID 8673113. 
  • Dailey TA, Dailey HA (1996). "Human protoporphyrinogen oxidase: expression, purification, and characterization of the cloned enzyme". Protein Sci. 5 (1): 98–105. doi:10.1002/pro.5560050112. PMC 2143237. PMID 8771201. 
  • Puy H; Robréau AM; Rosipal R et al. (1996). "Protoporphyrinogen oxidase: complete genomic sequence and polymorphisms in the human gene". Biochem. Biophys. Res. Commun. 226 (1): 226–30. doi:10.1006/bbrc.1996.1337. PMID 8806618. 
  • Deybach JC; Puy H; Robréau AM et al. (1997). "Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria". Hum. Mol. Genet. 5 (3): 407–10. doi:10.1093/hmg/5.3.407. PMID 8852667. 
  • Lam H; Dragan L; Tsou HC et al. (1997). "Molecular basis of variegate porphyria: a de novo insertion mutation in the protoporphyrinogen oxidase gene". Hum. Genet. 99 (1): 126–9. doi:10.1007/s004390050325. PMID 9003509. 
  • Dailey HA, Dailey TA (1997). "Characteristics of human protoporphyrinogen oxidase in controls and variegate porphyrias". Cell. Mol. Biol. (Noisy-le-grand) 43 (1): 67–73. PMID 9074790. 
  • Frank J, Poh-Fitzpatrick MB, King LE, Christiano AM (1998). "The genetic basis of "Scarsdale Gourmet Diet" variegate porphyria: a missense mutation in the protoporphyrinogen oxidase gene". Arch. Dermatol. Res. 290 (8): 441–5. doi:10.1007/s004030050333. PMID 9763307. 
  • Roberts AG; Puy H; Dailey TA et al. (1998). "Molecular characterization of homozygous variegate porphyria". Hum. Mol. Genet. 7 (12): 1921–5. doi:10.1093/hmg/7.12.1921. PMID 9811936. 
  • Whatley SD; Puy H; Morgan RR et al. (2000). "Variegate Porphyria in Western Europe: Identification of PPOX Gene Mutations in 104 Families, Extent of Allelic Heterogeneity, and Absence of Correlation between Phenotype and Type of Mutation". Am. J. Hum. Genet. 65 (4): 984–94. doi:10.1086/302586. PMC 1288269. PMID 10486317. 
  • Suzuki Y; Ishihara D; Sasaki M et al. (2000). "Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries". Genomics 64 (3): 286–97. doi:10.1006/geno.2000.6076. PMID 10756096. 
  • Corrigall AV; Hift RJ; Davids LM et al. (2000). "Homozygous variegate porphyria in South Africa: genotypic analysis in two cases". Mol. Genet. Metab. 69 (4): 323–30. doi:10.1006/mgme.2000.2975. PMID 10870850. 
  • Kauppinen R; Timonen K; von und zu Fraunberg M et al. (2001). "Homozygous variegate porphyria: 20 y follow-up and characterization of molecular defect". J. Invest. Dermatol. 116 (4): 610–3. doi:10.1046/j.1523-1747.2001.01293.x. PMID 11286631. 
  • Palmer RA, Elder GH, Barrett DF, Keohane SG (2001). "Homozygous variegate porphyria: a compound heterozygote with novel mutations in the protoporphyrinogen oxidase gene". Br. J. Dermatol. 144 (4): 866–9. doi:10.1046/j.1365-2133.2001.04147.x. PMID 11298551. 
  • Corrigall AV; Hift RJ; Davids LM et al. (2001). "Identification of the first variegate porphyria mutation in an indigenous black South African and further evidence for heterogeneity in variegate porphyria". Mol. Genet. Metab. 73 (1): 91–6. doi:10.1006/mgme.2001.3163. PMID 11350188. 
  • Donnelly JG, Detombe S, Hindmarsh JT (2002). "Single-strand conformational polymorphism and denaturing gradient gel electrophoresis in screening for variegate porphyria: identification of two new mutations". Ann. Clin. Lab. Sci. 32 (2): 107–13. PMID 12017191. 

External links[edit]