POR

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 play a critical role in the formation of steroid hormones, which 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.

cytochrome P450 oxidoreductase deficiency - caused by mutations in the POR gene

More than 50 mutations in the POR gene have been found to cause cytochrome P450 oxidoreductase deficiency. Most of these mutations change single protein building blocks (amino acids) used to make cytochrome P450 oxidoreductase. POR gene mutations significantly reduce the enzyme's activity, which impairs the cytochrome P450 enzymes and disrupts the production of steroid hormones. Changes in sex hormones such as testosterone and estrogen lead to problems with sexual development before birth and at puberty.

It is less clear how impairment of cytochrome P450 oxidoreductase leads to the skeletal abnormalities seen in severe cases of cytochrome P450 oxidoreductase deficiency. Studies suggest that these abnormalities may be related, at least in part, to the abnormal production of cholesterol. Cholesterol is a substance that is altered to produce steroid hormones. It is necessary for normal embryonic development and is involved in bone formation.

It is also 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.