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Normal Function
The POR gene provides instructions for making the enzyme cytochrome P450 oxidoreductase. This enzyme is required for the normal functioning of more than 50 enzymes in the cytochrome P450 family. Cytochrome P450 enzymes are involved in the formation (synthesis) and breakdown (metabolism) of various molecules and chemicals within cells.
Cytochrome P450 enzymes are critical for the synthesis of cholesterol and steroid hormones. Cholesterol is a substance that has many essential functions both before and after birth, including roles in the production of steroid hormones and in the formation and growth of bones. Steroid hormones are needed for normal development and reproduction. This group of hormones includes testosterone and estrogen, which are essential for normal sexual development and reproduction; corticosteroids, which are involved in the body's response to stress; and aldosterone, which helps regulate the body's salt and water balance.
Additionally, cytochrome P450 enzymes are involved in the metabolism of ingested substances, such as medications, in the liver. Because cytochrome P450 oxidoreductase helps regulate the activity of these enzymes, researchers suspect that normal variations in the POR gene may influence a person's response to particular drugs (drug metabolism).
Health Conditions Related to Genetic Changes
Cytochrome P450 oxidoreductase deficiency
More than 50 mutations in the POR gene have been found to cause cytochrome P450 oxidoreductase deficiency. This condition causes hormonal changes that can affect the development of the reproductive system, skeleton, and other parts of the body. The disorder affects sexual development before birth and at puberty, and severe cases are also characterized by skeletal abnormalities.
Most of the mutations that cause cytochrome P450 oxidoreductase deficiency change single protein building blocks (amino acids) in cytochrome P450 oxidoreductase. POR gene mutations significantly reduce the enzyme's activity, which disrupts the production of steroid hormones. Changes in sex hormones such as testosterone and estrogen lead to problems with sexual development.
Reduced activity of cytochrome P450 oxidoreductase can also disrupt the production of cholesterol, which likely impairs normal bone formation in severe cases of cytochrome P450 oxidoreductase deficiency. Studies suggest that a molecule called retinoic acid also plays a role in the skeletal abnormalities found in severe cases. The breakdown of retinoic acid requires cytochrome P450 oxidoreductase; if a shortage of cytochrome P450 oxidoreductase prevents retinoic acid from being broken down, the resulting excess of that molecule can stimulate the abnormal growth and fusion of bones.
It is unclear whether mutations in the POR gene affect how the liver processes medications. The role of this enzyme in drug metabolism is an active area of research.
More About This Health ConditionOther Names for This Gene
- CPR
- CYPOR
- cytochrome P450 reductase
- FLJ26468
- NADPH-dependent cytochrome P450 reductase
- NCPR_HUMAN
- P450 (cytochrome) oxidoreductase
- P450R
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, Chalder SM, Borucka-Mankiewicz M, Hauffa BP, Malunowicz EM, Stewart PM, Shackleton CH. Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. Lancet. 2004 Jun 26;363(9427):2128-35. doi: 10.1016/S0140-6736(04)16503-3. Citation on PubMed
- Fluck CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonca BB, Fujieda K, Miller WL. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet. 2004 Mar;36(3):228-30. doi: 10.1038/ng1300. Epub 2004 Feb 1. Citation on PubMed
- Fukami M, Horikawa R, Nagai T, Tanaka T, Naiki Y, Sato N, Okuyama T, Nakai H, Soneda S, Tachibana K, Matsuo N, Sato S, Homma K, Nishimura G, Hasegawa T, Ogata T. Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients. J Clin Endocrinol Metab. 2005 Jan;90(1):414-26. doi: 10.1210/jc.2004-0810. Epub 2004 Oct 13. Citation on PubMed
- Hart SN, Zhong XB. P450 oxidoreductase: genetic polymorphisms and implications for drug metabolism and toxicity. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):439-52. doi: 10.1517/17425255.4.4.439. Citation on PubMed
- Huang N, Agrawal V, Giacomini KM, Miller WL. Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1733-8. doi: 10.1073/pnas.0711621105. Epub 2008 Jan 29. Citation on PubMed or Free article on PubMed Central
- Huang N, Pandey AV, Agrawal V, Reardon W, Lapunzina PD, Mowat D, Jabs EW, Van Vliet G, Sack J, Fluck CE, Miller WL. Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Am J Hum Genet. 2005 May;76(5):729-49. doi: 10.1086/429417. Epub 2005 Mar 25. Citation on PubMed or Free article on PubMed Central
- Miller WL, Huang N, Agrawal V, Giacomini KM. Genetic variation in human P450 oxidoreductase. Mol Cell Endocrinol. 2009 Mar 5;300(1-2):180-4. doi: 10.1016/j.mce.2008.09.017. Epub 2008 Sep 26. Citation on PubMed
- Sim SC, Miller WL, Zhong XB, Arlt W, Ogata T, Ding X, Wolf CR, Fluck CE, Pandey AV, Henderson CJ, Porter TD, Daly AK, Nebert DW, Ingelman-Sundberg M. Nomenclature for alleles of the cytochrome P450 oxidoreductase gene. Pharmacogenet Genomics. 2009 Jul;19(7):565-6. doi: 10.1097/FPC.0b013e32832af5b7. No abstract available. Citation on PubMed or Free article on PubMed Central
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