CYP27B1

CYP27B1 is the gene that encodes 25-hydroxyvitamin D3 1-alpha-hydroxylase, a mitochondrial enzyme of the cytochrome P450 family that converts circulating 25-hydroxyvitamin D3 (25(OH)D3) into the active metabolite 1,25-dihydroxyvitamin D3 (calcitriol). The reaction occurs primarily in the kidney’s proximal tubules, where it plays a central role in calcium and phosphate homeostasis, though the enzyme is also expressed in other tissues and immune cells under certain conditions.

The activity of CYP27B1 is tightly regulated by hormonal and nutritional signals. Parathyroid hormone stimulates renal CYP27B1 expression and activity, increasing calcitriol production when calcium levels are low. Conversely, fibroblast growth factor 23 and circulating calcitriol feedback to suppress CYP27B1, forming a regulatory loop. Inflammation can induce extrarenal production of calcitriol by macrophages and other cells, contributing to local and sometimes systemic effects.

Clinical significance is most prominently illustrated by autosomal recessive mutations in CYP27B1, which cause vitamin D–dependent rickets type 1 (VDDR1). This disorder presents with hypocalcemia, hypophosphatemia, rickets, and growth delay in infancy or childhood. Because the enzymatic step is impaired, patients typically have low calcitriol despite adequate 25(OH)D levels. Treatment with active vitamin D (calcitriol) bypasses the deficiency and improves biochemical and skeletal outcomes.

Genetically, CYP27B1 belongs to the cytochrome P450 superfamily and is relevant to both mineral metabolism and immune system function through its extrarenal expression and activity.