CYP24A1

CYP24A1 is a human gene that encodes the enzyme 24-hydroxylase, a member of the cytochrome P450 family. It plays a key role in the catabolism and inactivation of vitamin D metabolites by adding a hydroxyl group at the 24 position, converting 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D into their 24-hydroxylated forms, which are further metabolized to calcitroic acid for excretion. The gene is located on chromosome 20q13.3 and is expressed in multiple tissues, with notable activity in the kidney. Expression of CYP24A1 is upregulated by active vitamin D signaling.

Function and regulation: CYP24A1 localizes to the endoplasmic reticulum membrane and requires NADPH and oxygen for catalytic activity. It preferentially hydroxylates 25(OH)D3 and 1,25(OH)2D3, initiating their inactivation and maintaining a negative feedback loop that limits vitamin D signaling. Transcription of CYP24A1 is induced by the vitamin D receptor (VDR) in response to circulating levels of 1,25(OH)2D3, helping to regulate calcium and phosphate homeostasis.

Clinical significance: Pathogenic variants in CYP24A1 cause autosomal recessive infantile hypercalcemia, a condition characterized by severe hypercalcemia in infancy and, in some cases, dehydration and growth issues. In later life, disruption of CYP24A1 can affect vitamin D metabolism and may increase risk of hypercalcemia or nephrolithiasis under high vitamin D intake. Common genetic variation may modulate circulating vitamin D metabolites and individual responses to supplementation.

In disease and therapy research, CYP24A1 overexpression can reduce the effectiveness of vitamin D–based anticancer treatments, prompting interest in CYP24A1 inhibitors to enhance therapeutic responses.