A cytochrome P450 monooxygenase involved in activation of vitamin D precursors. Catalyzes hydroxylation at C-25 of both forms of vitamin D, vitamin D(2) and D(3) (calciol) (PubMed:12867411, PubMed:15465040, PubMed:18511070). Can metabolize vitamin D analogs/prodrugs 1alpha-hydroxyvitamin D(2) (doxercalciferol) and 1alpha-hydroxyvitamin D(3) (alfacalcidol) forming 25-hydroxy derivatives (PubMed:15465040, PubMed:18511070). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:12867411, PubMed:15465040, PubMed:18511070). calciol + O2 + reduced [NADPH--hemoprotein reductase] = calcidiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] O2 + reduced [NADPH--hemoprotein reductase] + vitamin D2 = 25-hydroxyvitamin D2 + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 1alpha-hydroxyvitamin D2 + O2 + reduced [NADPH--hemoprotein reductase] = 1alpha,25-dihydroxyvitamin D2 + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] alfacalcidol + O2 + reduced [NADPH--hemoprotein reductase] = calcitriol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] Hormone biosynthesis; vitamin D biosynthesis. Homodimer. The disease is caused by variants affecting the gene represented in this entry. Belongs to the cytochrome P450 family.