POR Gene: Function, Mutations, and Associated Diseases | Cytochrome P450 Oxidoreductase

The POR gene encodes the enzyme cytochrome P450 oxidoreductase (POR), a crucial membrane-bound flavoprotein that serves as the universal electron donor for all microsomal cytochrome P450 (CYP) enzymes. These CYP enzymes are involved in the metabolism of a vast array of endogenous and exogenous compounds, including drugs, steroids, fatty acids, and xenobiotics. POR transfers electrons from NADPH to CYP enzymes, enabling their catalytic activity. This process is essential for various physiological functions, including steroid hormone synthesis, cholesterol biosynthesis, drug detoxification, and the metabolism of retinoic acid. Mutations in the POR gene can lead to a spectrum of disorders, most notably Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Steroid hormone biosynthesis

• Cholesterol metabolism

• Drug metabolism - cytochrome P450

• Retinoic acid metabolism

• Xenobiotics metabolism

The POR protein is a 82 kDa endoplasmic reticulum membrane-bound flavoprotein. It contains two flavin cofactors, FAD and FMN, which are essential for its electron transfer function. The protein is composed of several domains: an N-terminal membrane-binding domain, a FMN-binding domain, a connecting domain, and a C-terminal FAD/NADPH-binding domain. POR accepts electrons from NADPH via FAD and transfers them one at a time to the heme iron of various microsomal CYP enzymes. This electron transfer is the rate-limiting step in many CYP-catalyzed reactions. The crystal structure of rat POR has been solved, revealing a hinge-like motion that allows the FMN domain to interact with different CYP partners.