This gene encodes the nuclear hormone receptor for vitamin D3. The active metabolite of vitamin D modulates the expression of a wide variety of genes in a developmentally specific manner. The receptor belongs to the family of trans-acting transcriptional regulatory factors and shows sequence similarity to the steroid and thyroid hormone receptors. This secosteroid hormone can up- or downregulate the expression of genes involved in a diverse array of responses such as proliferation, differentiation and calcium homeostasis. 1,25- (OH)2-vitamin D3 exerts its effects through interaction with the vitamin D receptor (VDR), a member of the superfamily of hormone-activated nuclear receptors. In its ligand-bound state, the VDR forms heterodimers with the 9-cis retinoic acid receptor, RXR, and affects gene expression by binding specific DNA sequences known as hormone response elements, or HREs. In addition to regulating the above-mentioned cellular responses, 1,25- (OH)2-vitamin D3 exhibits antiproliferative properties in osteosarcoma, melanoma, colon carcinoma and breast carcinoma cells. Mutations in this gene are associated with type II vitamin D-resistant rickets. A single nucleotide polymorphism in the initiation codon results in an alternate translation start site three codons downstream. Alternative splicing results in multiple transcript variants encoding different proteins.