CYP2R1 Gene

HGNC Family	Cytochrome P450s (CYP)
Name	cytochrome P450, family 2, subfamily R, polypeptide 1
Description	This gene encodes 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. This enzyme is a microsomal vitamin D hydroxylase that converts vitamin D into the active ligand for the vitamin D receptor. A mutation in this gene has been associated with selective 25-hydroxyvitamin D deficiency. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CYP2R1 is a microsomal cytochrome P450 enzyme that plays a central role in vitamin D homeostasis by catalyzing the 25‐hydroxylation of vitamin D₃ into 25‐hydroxyvitamin D₃, the major circulating metabolite required for subsequent activation to its hormonal form. Its primary localization in the liver (with additional expression in tissues such as the testis) underscores its critical function in initiating vitamin D activation (see, for example."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Genome‐wide association studies and functional analyses have identified multiple common genetic variants in and near CYP2R1 that are robustly associated with serum 25(OH)D concentrations and, consequently, with altered vitamin D status and risk of conditions such as vitamin D insufficiency, rickets, type 1 diabetes, and other chronic diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " In addition, animal studies using CYP2R1‐deficient mice have demonstrated that loss of CYP2R1 function results in a marked reduction in circulating 25(OH)D levels, thereby confirming its role as the major enzyme responsible for vitamin D 25‐hydroxylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Biochemical comparisons reveal that CYP2R1 exhibits a narrow substrate specificity with higher catalytic efficiency for vitamin D₃ than other potential 25‐hydroxylases such as CYP27A1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and structural studies have provided insight into its active site architecture, rationalizing how specific mutations in CYP2R1 can lead to inherited forms of vitamin D deficiency and rickets."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, variations in CYP2R1 not only affect basal vitamin D status but also appear to modify the response to vitamin D acquisition by influencing the degree of conversion following ultraviolet B irradiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these findings establish CYP2R1 as a key regulator of vitamin D bioactivation and a potential genetic determinant of individual differences in vitamin D status and related health outcomes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jeffrey B Cheng, Daniel L Motola, David J Mangelsdorf, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307028200"}], "href": "https://doi.org/10.1074/jbc.M307028200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12867411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12867411"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Thomas J Wang, Feng Zhang, J Brent Richards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common genetic determinants of vitamin D insufficiency: a genome-wide association study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0140-6736(10)60588-0"}], "href": "https://doi.org/10.1016/S0140-6736(10"}, {"type": "t", "text": "60588-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20541252"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20541252"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jiyoung Ahn, Kai Yu, Rachael Stolzenberg-Solomon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of circulating vitamin D levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddq155"}], "href": "https://doi.org/10.1093/hmg/ddq155"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20418485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20418485"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Elizabeth Ramos-Lopez, Patrick Brück, Thomas Jansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Metab Res Rev (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dmrr.719"}], "href": "https://doi.org/10.1002/dmrr.719"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17607662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17607662"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jinge G Zhu, Justin T Ochalek, Martin Kaufmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1315006110"}], "href": "https://doi.org/10.1073/pnas.1315006110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24019477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24019477"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Raku Shinkyo, Toshiyuki Sakaki, Masaki Kamakura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metabolism of vitamin D by human microsomal CYP2R1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2004.09.073"}], "href": "https://doi.org/10.1016/j.bbrc.2004.09.073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15465040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15465040"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Natallia Strushkevich, Sergey A Usanov, Alexander N Plotnikov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural analysis of CYP2R1 in complex with vitamin D3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2008.03.065"}], "href": "https://doi.org/10.1016/j.jmb.2008.03.065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18511070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18511070"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Angham N Al Mutair, Ghada H Nasrat, David W Russell "}, {"type": "b", "children": [{"type": "t", "text": "Mutation of the CYP2R1 vitamin D 25-hydroxylase in a Saudi Arabian family with severe vitamin D deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2012-1340"}], "href": "https://doi.org/10.1210/jc.2012-1340"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22855339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22855339"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Janna Nissen, Ulla Vogel, Gitte Ravn-Haren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D₃-fortified bread and milk during winter in Denmark."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Clin Nutr (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3945/ajcn.114.092148"}], "href": "https://doi.org/10.3945/ajcn.114.092148"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25527766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25527766"}]}]}]}
Proteins	CP2R1_HUMAN
NCBI Gene ID	120227
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CYP2R1 has 5,701 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 117 datasets.

Click the + buttons to view associations for CYP2R1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CYP2R1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CYP2R1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CYP2R1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CYP2R1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CYP2R1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CYP2R1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CYP2R1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CYP2R1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CYP2R1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CYP2R1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CYP2R1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CYP2R1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CYP2R1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CYP2R1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CYP2R1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CYP2R1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CYP2R1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CYP2R1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CYP2R1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CYP2R1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CYP2R1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CYP2R1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CYP2R1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CYP2R1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CYP2R1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CYP2R1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CYP2R1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CYP2R1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CYP2R1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CYP2R1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CYP2R1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CYP2R1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CYP2R1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CYP2R1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CYP2R1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CYP2R1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CYP2R1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CYP2R1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CYP2R1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CYP2R1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CYP2R1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.