Vitamin D 25-hydroxylase also known as cytochrome P450 2R1 is an enzyme that in humans is encoded by the CYP2R1 gene.  
Function [ edit ]
Vitamin D 25-hydroxylase is a member of the
cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Found in the liver, this enzyme is a microsomal vitamin D hydroxylase that converts vitamin D into 25-hydroxyvitamin D (calcidiol), which is the major circulatory form of the vitamin.
Clinical significance [ edit ]
mutation in the CYP2R1 gene which results in the substitution of a proline for a leucine residue at codon 99 eliminates the enzyme activity and is associated with low circulating levels of 25-hydroxyvitamin D and classic symptoms of vitamin D deficiency. The gene product which it encodes, vitamin D 25-hydroxylase, has therefore been proposed as the key enzyme in the conversion of  cholecalciferol (vitamin D 3) to calcidiol. Calcidiol is subsequently converted by the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase to calcitriol, the active form of vitamin D 3 that binds to the vitamin D receptor (VDR) which mediates most of the physiological actions of the vitamin.
Conversion of cholecalciferol to calcidiol as catalyzed by CYP2R1.
Interactive pathway map [ edit ]
Click on genes, proteins and metabolites below to link to respective articles.
Vitamin D Synthesis Pathway (
Model organisms [ edit ]
Model organisms have been used in the study of CYP2R1 function. A conditional knockout mouse line called Cyp2r1 was generated at the tm1b(EUCOMM)Wtsi Wellcome Trust Sanger Institute. Male and female animals underwent a standardized  phenotypic screen to determine the effects of deletion.     Additional screens performed: - In-depth immunological phenotyping 
References [ edit ]
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GRCh38: Ensembl release 89: ENSG00000186104 - Ensembl, May 2017
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GRCm38: Ensembl release 89: ENSMUSG00000030670 - Ensembl, May 2017
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"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Nelson DR (Dec 2002). "Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution". Arch Biochem Biophys. 409 (1): 18–24. doi: 10.1016/S0003-9861(02)00553-2. PMID 12464240.
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Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW (2004-05-18). "Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase". Proc Natl Acad Sci U S A. 101 (20): 7711–7715. Bibcode: 2004PNAS..101.7711C. doi: 10.1073/pnas.0402490101. PMC . 419671 PMID 15128933.
"Entrez Gene: CYP2R1 cytochrome P450, family 2, subfamily R, polypeptide 1".
Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi: 10.1111/j.1755-3768.2010.4142.x.
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Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi: 10.1038/nature10163. PMC . 3572410 PMID 21677750.
Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a. PMID 21677718.
Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi: 10.1016/j.cell.2006.12.018. PMID 17218247.
White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi: 10.1016/j.cell.2013.06.022. PMC . 3717207 PMID 23870131.
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"Infection and Immunity Immunophenotyping (3i) Consortium".
Further reading [ edit ]
Ramos-Lopez E, Brück P, Jansen T, et al. (2008). "CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans". Diabetes Metab. Res. Rev. 23 (8): 631–6. doi: 10.1002/dmrr.719. PMID 17607662.
Ramos-Lopez E, Brück P, Jansen T, et al. (2007). "CYP2R1-, CYP27B1- and CYP24-mRNA expression in German type 1 diabetes patients". J. Steroid Biochem. Mol. Biol. 103 (3–5): 807–10. doi: 10.1016/j.jsbmb.2006.12.056. PMID 17223345.
Wjst M, Altmüller J, Faus-Kessler T, et al. (2006). "Asthma families show transmission disequilibrium of gene variants in the vitamin D metabolism and signalling pathway". Respir. Res. 7: 60. doi: 10.1186/1465-9921-7-60. PMC . 1508148 PMID 16600026.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi: 10.1101/gr.2596504. PMC . 528928 PMID 15489334.
Shinkyo R, Sakaki T, Kamakura M, et al. (2004). "Metabolism of vitamin D by human microsomal CYP2R1". Biochem. Biophys. Res. Commun. 324 (1): 451–7. doi: 10.1016/j.bbrc.2004.09.073. PMID 15465040.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285. PMID 14702039. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode: 2002PNAS...9916899M. doi: 10.1073/pnas.242603899. PMC . 139241 PMID 12477932.
External links [ edit ]