CYP2R1

Vitamin D 25-hydroxylase also known as cytochrome P450 2R1 is an is_associated_with::enzyme that in humans is encoded by the CYP2R1 is_associated_with::gene.

Function
Vitamin D 25-hydroxylase is a member of the is_associated_with::cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Found in the liver, this enzyme is a microsomal vitamin D hydroxylase that converts is_associated_with::vitamin D into 25-hydroxyvitamin D (calcidiol), which is the major circulatory form of the vitamin.

Clinical significance
An inherited is_associated_with::mutation in the CYP2R1 gene which results in the substitution of a is_associated_with::proline for a is_associated_with::leucine residue at is_associated_with::codon 99 eliminates the enzyme activity and is associated with low circulating levels of 25-hydroxyvitamin D and classic symptoms of is_associated_with::vitamin D deficiency. The gene product which it encodes, vitamin D 25-hydroxylase, has therefore been proposed as the key enzyme in the conversion of is_associated_with::cholecalciferol (vitamin D3) to is_associated_with::calcidiol. Calcidiol is subsequently converted by the action of is_associated_with::25-hydroxyvitamin D3 1-alpha-hydroxylase to is_associated_with::calcitriol, the active form of vitamin D3 that binds to the vitamin D receptor (VDR) which mediates most of the physiological actions of the vitamin.

Model organisms
is_associated_with::Model organisms have been used in the study of CYP2R1 function. A conditional is_associated_with::knockout mouse line called Cyp2r1tm1b(EUCOMM)Wtsi was generated at the is_associated_with::Wellcome Trust Sanger Institute. Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping