CYP2R1

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

Vitamin D 25-hydroxylase also known as cytochrome P450 2R1 is an enzyme that in humans is encoded by the CYP2R1 gene.

Function

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

An inherited 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 D₃) to calcidiol. Calcidiol is subsequently converted by the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase to calcitriol, the active form of vitamin D₃ that binds to the vitamin D receptor (VDR) which mediates most of the physiological actions of the vitamin.

File:Reaction - cholecalciferol to calcidiol (vertical).png Conversion of cholecalciferol to calcidiol as catalyzed by CYP2R1.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

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<imagemap> Image:VitaminDSynthesis WP1531.png

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<imagemap> Image:VitaminDSynthesis WP1531.png

|{{{bSize}}}px|alt=Vitamin D Synthesis Pathway (view / edit)]]

Vitamin D Synthesis Pathway (view / edit)

Model organisms

Model organisms have been used in the study of CYP2R1 function. A conditional knockout mouse line called Cyp2r1^{tm1b(EUCOMM)Wtsi} was generated at the 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

Cyp2r1 knockout mouse phenotype

Characteristic	Phenotype
All data available at.
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

Further reading

• 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

• Human CYP2R1 genome location and CYP2R1 gene details page in the UCSC Genome Browser.