Vitamin D receptor (VDR)

The Vitamin D receptor is a nuclear hormone receptor that functions as a ligand-dependent transcription factor. Upon binding its primary endogenous ligand—calcitriol—it forms a heterodimer with the retinoid X receptor. This complex translocates into the nucleus where it binds specific DNA sequences called vitamin D response elements, regulating expression of genes involved in mineral metabolism (notably calcium and phosphate), immune responses, cell proliferation/differentiation/apoptosis pathways, hair follicle cycling, among others. The VDR protein contains distinct domains for DNA binding and ligand binding; its structure has been well characterized by crystallography studies. The gene encoding human VDR is located on chromosome 12q13.11. Variants in this gene have been associated with altered susceptibility to several diseases including osteoporosis/osteomalacia/rickets due to impaired bone mineralization; autoimmune conditions; certain cancers; infectious disease progression such as HIV/AIDS; among others. Drugs that activate the VDR are used therapeutically primarily for disorders involving abnormal calcium/phosphate balance but are being explored for broader indications due to their immunomodulatory effects.

Other names

Calcitriol receptorNuclear vitamin D3 receptor1,25-dihydroxyvitamin D3 receptor

Drugs targeting the vitamin D receptor typically act as agonists. They bind to the ligand-binding domain of VDR, promoting heterodimerization with retinoid X receptor (RXR), which then binds to vitamin D response elements in DNA to regulate transcription of target genes involved in calcium/phosphate metabolism, immune function, cell proliferation/differentiation, and other processes.