VDR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1DB1, 1IE8, 1IE9, 1KB2, 1KB4, 1KB6, 1S0Z, 1S19, 1TXI, 1YNW, 2HAM, 2HAR, 2HAS, 2HB7, 2HB8, 3A2I, 3A2J, 3A3Z, 3A40, 3A78, 3AUQ, 3AUR, 3AX8, 3AZ1, 3AZ2, 3AZ3, 3B0T, 3CS4, 3CS6, 3KPZ, 3M7R, 3OGT, 3P8X, 3TKC, 3VHW, 4G2I, 3W0A, 3W0C, 3W0Y, 3WGP, 3WWR, 4ITE, 4ITF, 4PA2, 3X31, 3X36, 4FHH, 4FHI, 2HBH
Identifiers
Aliases	VDR, NR1I1, PPP1R163, vitamin D (1,25- dihydroxyvitamin D3) receptor, vitamin D receptor
External IDs	OMIM: 601769 MGI: 103076 HomoloGene: 37297 GeneCards: VDR
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.11 Start 47,841,537 bp[1] End 47,943,048 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 F1 Start 97,752,306 bp[2] End 97,808,511 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibia hair follicle jejunal mucosa duodenum periodontal fiber rectum spongy bone gums palpebral conjunctiva kidney tubule Top expressed in duodenum lip large intestine colon crypt of lieberkuhn of small intestine left colon Paneth cell jejunum islet of Langerhans kidney More reference expression data BioGPS More reference expression data
Gene ontology Molecular function lithocholic acid binding sequence-specific DNA binding DNA binding lithocholic acid receptor activity nuclear receptor activity steroid hormone receptor activity protein binding DNA-binding transcription factor activity zinc ion binding metal ion binding vitamin D response element binding retinoid X receptor binding calcitriol binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription cis-regulatory region binding RNA polymerase II transcription regulatory region sequence-specific DNA binding vitamin D binding transcription factor binding nuclear receptor coactivator activity signaling receptor activity Cellular component nucleus nucleoplasm receptor complex RNA polymerase II transcription regulator complex cytoplasm Biological process negative regulation of cell population proliferation positive regulation of apoptotic process involved in mammary gland involution positive regulation of keratinocyte differentiation regulation of calcidiol 1-monooxygenase activity intestinal absorption calcium ion transport steroid hormone mediated signaling pathway regulation of transcription, DNA-templated lactation bile acid signaling pathway animal organ morphogenesis cell morphogenesis skeletal system development positive regulation of gene expression positive regulation of transcription by RNA polymerase II multicellular organism development negative regulation of keratinocyte proliferation decidualization negative regulation of transcription by RNA polymerase II negative regulation of transcription, DNA-templated transcription initiation from RNA polymerase II promoter positive regulation of vitamin D 24-hydroxylase activity mammary gland branching involved in pregnancy signal transduction cellular calcium ion homeostasis transcription, DNA-templated vitamin D receptor signaling pathway vitamin D metabolic process cell differentiation intracellular receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7421 22337 Ensembl ENSG00000111424 ENSMUSG00000022479 UniProt P11473 P48281 RefSeq (mRNA) NM_000376 NM_001017535 NM_001017536 NM_001364085 NM_001374661 NM_001374662 NM_009504 RefSeq (protein) NP_000367 NP_001017535 NP_001017536 NP_001351014 NP_001361590 NP_001361591 NP_033530 Location (UCSC) Chr 12: 47.84 – 47.94 Mb Chr 15: 97.75 – 97.81 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors.^[5] Calcitriol (the active form of vitamin D, 1,25-(OH)₂vitamin D₃) binds to VDR, which then forms a heterodimer with the retinoid-X receptor. The VDR heterodimer then enters the nucleus and binds to Vitamin D responsive elements (VDRE) in genomic DNA. VDR binding results in expression or transrepression of many specific gene products. VDR is also involved in microRNA-directed post transcriptional mechanisms.^[6] In humans, the vitamin D receptor is encoded by the VDR gene located on chromosome 12q13.11.^[7]

VDR is expressed in most tissues of the body, and regulates transcription of genes involved in intestinal and renal transport of calcium and other minerals.^[8] Glucocorticoids decrease VDR expression.^[8] Many types of immune cells also express VDR.^[9]

Function

The VDR gene encodes the nuclear hormone receptor for vitamin D. The most potent natural agonist is calcitriol (1,25-dihydroxycholecalciferol) and the vitamin D₂ homologue ercalcitriol, 1-alpha,25-dihydroergocalciferol) is also a strong activator. Other forms of vitamin D bind with lower affinity, as does the secondary bile acid lithocholic acid. The receptor belongs to the family of trans-acting transcriptional regulatory factors and shows similarity of sequence to the steroid and thyroid hormone receptors.^[10]

Downstream targets of this nuclear hormone receptor include many genes involved in mineral metabolism.^[8] The receptor regulates a variety of other metabolic pathways, such as those involved in the immune response and cancer.^[9] VDR variants that bolster vitamin-D action and that are directly correlated with AIDS progression rates and VDR association with progression to AIDS follows an additive model.^[11] FokI polymorphism is a risk factor for enveloped virus infection as revealed in a meta-analysis.^[12] The importance of this gene has also been noted in the natural aging process were 3’UTR haplotypes of the gene showed an association with longevity.^[13]

Clinical relevance

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 the same protein.^[14] VDR gene variants seem to influence many biological endpoints, including those related to osteoporosis ^[15]

The vitamin D receptor plays an important role in regulating the hair cycle. Loss of VDR is associated with hair loss in experimental animals.^[16] Experimental studies have shown that the unliganded VDR interacts with regulatory regions in cWnt (wnt signaling pathway) and sonic hedgehog target genes and is required for the induction of these pathways during the postnatal hair cycle.^[17] These studies have revealed novel actions of the unliganded VDR in regulating the post-morphogenic hair cycle.

Researchers have focused their efforts in elucidating the role of VDR polymorphisms in different diseases and normal phenotypes such as the HIV-1 infection susceptibility and progression or the natural aging process. The most remarkable findings include the report of VDR variants that bolster vitamin-D action and that are directly correlated with AIDS progression rates, that VDR association with progression to AIDS follows an additive model^[11] and the role of FokI polymorphism as a risk factor for enveloped virus infection as revealed in a meta-analysis.^[12]

Interactions

Vitamin D receptor has been shown to interact with many other factors which will affect transcription activation:

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|alt=Vitamin D Synthesis Pathway (view / edit)]]

Vitamin D Synthesis Pathway (view / edit)

1. ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".