Cytochrome P450 2R1 (CYP2R1)

Cytochrome P450 2R1 (CYP2R1) is a microsomal enzyme in the cytochrome P450 superfamily responsible for the 25-hydroxylation of vitamin D in the liver, the essential first activation step in vitamin D metabolism. It converts both dietary and cutaneously synthesized vitamin D (vitamin D₃ and vitamin D₂) to 25-hydroxyvitamin D, the principal circulating form, which is used to assess vitamin D status clinically. Mutations in the CYP2R1 gene cause rare forms of vitamin D-deficiency rickets. CYP2R1 is highly selective for vitamin D as a substrate, localizes on chromosome 11p15.2, and has a typical P450 structure with specific substrate channel dynamics. CYP2R1 activity is essential for proper bone health, calcium/phosphate homeostasis, and prevention of bone softening diseases. No specific drugs target CYP2R1 for therapeutic purposes, but its function is critical for the efficacy of vitamin D supplementation and in rare cases of genetic deficiency may require specific medical intervention.

Other names

CYP2R1Cytochrome P450 2R1Vitamin D 25-hydroxylaseCytochrome P450, family 2, subfamily R, polypeptide 1Cytochrome P450, family 2, R1

Substrate hydroxylation: CYP2R1 catalyzes the conversion of vitamin D (D₃ or D₂) to 25-hydroxyvitamin D, enabling vitamin D activation cascade.