PPOX

Reviewed July 2009

What is the official name of the PPOX gene?

The official name of this gene is “protoporphyrinogen oxidase.”

PPOX is the gene's official symbol. The PPOX gene is also known by other names, listed below.

What is the normal function of the PPOX gene?

The PPOX gene provides instructions for making an enzyme known as protoporphyrinogen 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. Protoporphyrinogen oxidase is responsible for the seventh step in this process, in which two hydrogen atoms are removed from protoporphyrinogen IX (the product of the sixth step) to form protoporphyrin IX. In the final step, another enzyme modifies protoporphyrin IX by inserting an iron atom to produce heme.

How are changes in the PPOX gene related to health conditions?

porphyria - caused by mutations in the PPOX gene

More than 130 mutations in the PPOX gene have been identified in people with a form of porphyria called variegate porphyria. A particular PPOX gene mutation is found in about 95 percent of South African families with this form of the disorder. The mutation changes a single protein building block (amino acid) in protoporphyrinogen oxidase, replacing the amino acid arginine with the amino acid tryptophan at position 59 (written as Arg59Trp or R59W).

Mutations in the PPOX gene reduce the activity of protoporphyrinogen oxidase, allowing compounds called porphyrin precursors to build up in the body. These compounds are formed during the normal process of heme production, but reduced activity of protoporphyrinogen oxidase allows them to accumulate to toxic levels. Nongenetic factors such as certain drugs, alcohol, dieting, as well as other genetic factors that have not been identified, also contribute to the characteristic features of variegate porphyria.

Where is the PPOX gene located?

Cytogenetic Location: 1q22

Molecular Location on chromosome 1: base pairs 161,136,180 to 161,141,009

The PPOX gene is located on the long (q) arm of chromosome 1 at position 22.

More precisely, the PPOX gene is located from base pair 161,136,180 to base pair 161,141,009 on chromosome 1.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PPOX?

You and your healthcare professional may find the following resources about PPOX helpful.

Educational resources - Information pages
Biochemistry (fifth edition, 2002): Mammalian Porphyrins Are Synthesized from Glycine and Succinyl Coenzyme A (http://www.ncbi.nlm.nih.gov/books/NBK22446/)
Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK121283/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for PPOX (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=5498%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((PPOX%5BTIAB%5D)%20OR%20(protoporphyrinogen%20oxidase%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/600923)
Research Resources - Tools for researchers
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5498)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=5498)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=9280)

What other names do people use for the PPOX gene or gene products?

PPO
PPOX_HUMAN
protoporphyrinogenase
protoporphyrinogen dehydrogenase
protoporphyrinogen IX oxidase
protox

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PPOX?

amino acid ; atom ; bone marrow ; dehydrogenase ; enzyme ; gene ; heme ; hemoglobin ; iron ; molecule ; mutation ; oxidase ; oxygen ; porphyrin ; protein ; toxic

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Badminton MN, Elder GH. Molecular mechanisms of dominant expression in porphyria. J Inherit Metab Dis. 2005;28(3):277-86. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15868463?dopt=Abstract)
de Villiers JN, Kotze MJ, van Heerden CJ, Sadie A, Gardner HF, Liebenberg J, van Zyl R, du Plessis L, Kimberg M, Frank J, Warnich L. Overrepresentation of the founder PPOX gene mutation R59W in a South African patient with severe clinical manifestation of porphyria. Exp Dermatol. 2005 Jan;14(1):50-5. (http://www.ncbi.nlm.nih.gov/pubmed/15660919?dopt=Abstract)
Elder GH. Genetic defects in the porphyrias: types and significance. Clin Dermatol. 1998 Mar-Apr;16(2):225-33. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9554235?dopt=Abstract)
Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/5498)
Kauppinen R. Porphyrias. Lancet. 2005 Jan 15-21;365(9455):241-52. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15652607?dopt=Abstract)
Maneli MH, Corrigall AV, Klump HH, Davids LM, Kirsch RE, Meissner PN. Kinetic and physical characterisation of recombinant wild-type and mutant human protoporphyrinogen oxidases. Biochim Biophys Acta. 2003 Aug 21;1650(1-2):10-21. (http://www.ncbi.nlm.nih.gov/pubmed/12922165?dopt=Abstract)
Morgan RR, Errington R, Elder GH. Identification of sequences required for the import of human protoporphyrinogen oxidase to mitochondria. Biochem J. 2004 Jan 15;377(Pt 2):281-7. (http://www.ncbi.nlm.nih.gov/pubmed/14535846?dopt=Abstract)
Sassa S, Kappas A. Molecular aspects of the inherited porphyrias. J Intern Med. 2000 Feb;247(2):169-78. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10692079?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.