Vitamin D 25-hydroxylase (CYP2R1)

Vitamin D 25-hydroxylase, primarily encoded by the CYP2R1 gene, is a microsomal cytochrome P450 enzyme that serves as the principal catalyst for the first step of vitamin D activation in the liver (UniProt Q6VVX0). It performs the 25-hydroxylation of both vitamin D2 and D3 to produce 25-hydroxyvitamin D [25(OH)D], which is the major circulating form of the vitamin and the clinical standard for assessing vitamin D status (Cheng et al., 2003, J. Biol. Chem.). This enzymatic activity is vital for maintaining systemic calcium and phosphate levels necessary for proper bone mineralization and skeletal health. Mutations in the CYP2R1 gene are the primary cause of vitamin D-dependent rickets type 1B, a condition characterized by low circulating 25(OH)D despite adequate intake (Casella et al., 2008, J. Clin. Endocrinol. Metab.). While not a traditional target for small-molecule inhibition, it is a critical focal point for therapeutic supplementation strategies. In patients with hepatic dysfunction or genetic enzyme deficiency, the product calcifediol is often administered to bypass this metabolic step and restore vitamin D signaling (Rayaldee Prescribing Information).

Other names

Cytochrome P450 2R1CYP2R125-hydroxylaseMicrosomal vitamin D 25-hydroxylase

Enzymatic hydroxylation of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) at the C-25 position to form 25-hydroxyvitamin D [25(OH)D].