Cytochrome P450 Reductase, NADPH (POR) Active Protein

This gene encodes an endoplasmic reticulum membrane oxidoreductase with an FAD-binding domain and a flavodoxin-like domain. The protein binds two cofactors, FAD and FMN, which allow it to donate electrons directly from NADPH to all microsomal P450 enzymes. Mutations in this gene have been associated with various diseases, including apparent combined P450C17 and P450C21 deficiency, amenorrhea and disordered steroidogenesis, congenital adrenal hyperplasia and Antley-Bixler syndrome. [provided by RefSeq, Jul 2008]

POR: This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5. Defects in POR are the cause of Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (ABS1). A disease characterized by the association of Antley-Bixler syndrome with steroidogenesis defects and abnormal genitalia. Antley-Bixler syndrome is characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Defects in POR are the cause of disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency (DISPORD). A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome.

Protein type: Oxidoreductase; EC 1.6.2.4

Chromosomal Location of Human Ortholog: 7q11.2

Cellular Component: endoplasmic reticulum membrane; membrane; intracellular membrane-bound organelle; mitochondrion

Molecular Function: protein binding; enzyme binding; electron carrier activity; FAD binding; FMN binding; hydrolase activity; NADPH-hemoprotein reductase activity; nitric oxide dioxygenase activity; cytochrome-b5 reductase activity; iron ion binding; NADP binding; iron-cytochrome-c reductase activity

Biological Process: response to drug; nitric oxide catabolic process; internal peptidyl-lysine acetylation; positive regulation of monooxygenase activity; positive regulation of cholesterol biosynthetic process; negative regulation of caspase activity; negative regulation of lipase activity; nitrate catabolic process; positive regulation of chondrocyte differentiation; flavonoid metabolic process; positive regulation of smoothened signaling pathway; fatty acid oxidation; carnitine metabolic process; response to nutrient

Disease: Disordered Steroidogenesis Due To Cytochrome P450 Oxidoreductase Deficiency; Antley-bixler Syndrome With Genital Anomalies And Disordered Steroidogenesis; Antley-bixler Syndrome Without Genital Anomalies Or Disordered Steroidogenesis