P450 Oxidoreductase deficiency: Analysis of mutations and polymorphisms.

Burkhard, Fabian Z; Parween, Shaheena; Udhane, Sameer Sopanrao; Flück Pandey, Christa Emma; Pandey, Amit Vikram (2017). P450 Oxidoreductase deficiency: Analysis of mutations and polymorphisms. Journal of steroid biochemistry and molecular biology, 165(Pt A), pp. 38-50. Elsevier 10.1016/j.jsbmb.2016.04.003

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Cytochrome P450 oxidoreductase (POR) is required for metabolic reactions of steroid and drug metabolizing cytochrome P450 proteins located in endoplasmic reticulum. Mutations in POR cause a complex set of disorders resembling combined deficiencies of multiple steroid metabolizing enzymes. The P450 oxidoreductase deficiency (PORD) was first reported in patients with symptoms of defects in steroidogenic cytochrome P450 enzymes and ambiguous genitalia, and bone malformation features resembling Antley-Bixler syndrome. POR is now classified as a separate and rare form of congenital adrenal hyperplasia (CAH), which may cause disorder of sexual development (DSD). Since the initial description of PORD in 2004, a large number of POR mutations and polymorphisms have been described. In this report we have performed computational analysis of mutations and polymorphisms in POR linked to metabolism of steroids and xenobiotics and pathology of PORD from the reported cases. The mutations in POR that were identified in patients with disruption of steroidogenesis also have severe effects on cytochrome P450 proteins involved in metabolism of drugs. Different variations in POR show a range of diverse effects on different partner proteins that are often linked to the location of the particular variants. The variations in POR that cause defective binding of co-factors always have damaging effects on all partner proteins, while the mutations causing subtle structural changes may lead to altered interaction with partner proteins and the overall effect may be different for each individual partner. Computational analysis of available sequencing data and mutation analysis shows that Japanese (R457H), Caucasian (A287P) and Turkish (399-401) populations can be linked to unique founder mutations. Other mutations identified so far were identified as rare alleles or in single isolated reports. The common polymorphism of POR is the variant A503V which can be found in about 27% of alleles in general population but there are remarkable differences among different sub populations.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders

UniBE Contributor:

Parween, Shaheena, Udhane, Sameer Sopanrao, Flück Pandey, Christa Emma, Pandey, Amit Vikram


600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology






[4] Swiss National Science Foundation


[102] Pathogenesis of disorders caused by human P450 oxidoreductase mutations Official URL




Amit Vikram Pandey

Date Deposited:

22 Sep 2016 08:44

Last Modified:

06 Jan 2023 18:59

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Antley-Bixler syndrome; CYP17A1; Cytochrome P450 oxidoreductase; Disorders of sexual development; P450 oxidoreductase deficiency; PORD; Steroid metabolism





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