A cytochrome P450 monooxygenase involved in activation of vitamin D precursors. Catalyzes hydroxylation at C-25 of both forms of vitamin D, vitamin D(2) and D(3) (calciol). Can metabolize vitamin D analogs/prodrugs 1alpha-hydroxyvitamin D(2) (doxercalciferol) and 1alpha-hydroxyvitamin D(3) (alfacalcidol) forming 25-hydroxy derivatives. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).

1. Genetic variants of CYP2R1 are key determinants of serum 25OHD levels and are highly associated with myocardial infarction risk. The three studied SNPs were associated with significantly different total 25OHD levels and their genotype distributions differed significantly between MI patients and controls where the high risk genotypes were AG/AA for rs2060793, AG/GG for rs1993116 and AG/AA for rs10766197. PMID: 29804528
2. Published articles provide evidence supporting a major role for the rs10741657 polymorphism of the CYP2R1 gene in determining 25(OH)D levels and the presence of vitamin D deficiency. [review] PMID: 30120973
3. Results also showed for the first that polymorphisms of CYP2R1 gene (rs1993116 and rs10766197) were significantly associated with type 2 diabetes mellitus in a Chinese rural population. PMID: 30081191
4. No significant differences were found between ischemic stroke patients and controls in terms of CYP24A1 rs927650 and CYP2R1 rs10741657 genotype frequencies. Polymorphic allele frequencies of CYP24A1 rs927650 and CYP2R1 rs10741657 were 0.414 and 0.660 in stroke patients, respectively. PMID: 29528271
5. genetic association study in population in north India: Data suggest (1) GT allele of VDBP SNP rs7041, (2) VDBP allelic combination (GC1F/1F: T allele rs4588; C allele rs7041), and (3) GA allele of CYP2R1 SNP rs2060793 are associated with vitamin D deficiency in women with PCOS (polycystic ovarian syndrome) in population studied. (VDBP = vitamin D-binding protein; CYP2R1 = cytochrome P450 family 2 subfamily R member 1) PMID: 28008453
6. The results of this study suggested that a role of CYP2R1 rs10766197 in both risk and progression of Muscle sclerosis with sex-related differences. PMID: 28834557
7. CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency. PMID: 27473187
8. CYP3A4*22 and combined CYP3A genotypes are unlikely to provide additional information beyond CYP3A5 genotype. PMID: 27314545
9. This article concludes that mutations in CYP2R1 are responsible for an atypical form of vitamin D-deficiency rickets, which has been classified as vitamin D dependent rickets type 1B (VDDR1B, MIM 600081). [review] PMID: 27473561
10. The authors describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25-hydroxyvitamin D levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis. PMID: 28757204
11. Allelic variations in CYP2R1 and GC affect vitamin D levels, but variant alleles on VDR and DHCR7 were not correlated with vitamin D deficiency. PMID: 26038244
12. Expression of CYP2R1 was in spermatozoa from healthy controls compared with infertile men, however the percentage of spermatozoa expressing CYP2R1 was not significantly higher. PMID: 27977320
13. our study for the first time reports a potentially causative role of CYP2R1 mutation in Vogt-koyanagi-harada disease. PMID: 27716192
14. In a Pakistani population, no statistically significant associations between SNPs in VDR, DBP, and CYP2R1 and tuberculosis was demonstrated. PMID: 27160686
15. Vitamin D related (VDR rs2228570 and CYP2R1 rs10741657) and IL28B rs12979860 genes polymorphisms accurately assure sustained viral response in naive CHC G4 patients treated with low cost standard therapy. PMID: 26911666
16. The aim of this study was to investigate the association of three polymorphisms in the GC gene (rs7041 and rs4588) and CYP2R1 gene (rs10741657) on 25-(OH) VD serum concentration among Jordanians. PMID: 26383826
17. rs11023374 in CYP2R1 was significantly associated with serum 25(OH)D3. PMID: 26661839
18. The VDR and CYP2R1 variants may be involved in genetic interactions in the pathogenesis of persistent allergic rhinitis. PMID: 26177022
19. Significant associations were found between the GC (rs2282679 and rs7041), CYP2R1 (rs10741657) single nucleotide polymorphisms and the active form of Vitamin D, 25(OH)D. PMID: 25405862
20. The 25-hydroxylases CYP2R1 and CYP27A1 catalyze vitamin D to its circulating form 25-hydroxyvitamin D. PMID: 25845986
21. A significant association was found between decreased ASD risk and child CYP2R1 AA-genotype. PMID: 26073892
22. Found a significant upregulation of the CYP2R1 gene in human brain pericytes challenged with tumor necrosis factor-alpha and interferon-gamma. Results suggest the existence of an autocrine/paracrine vitamin D system in the neurovascular unit. PMID: 25730676
23. CYP2R1 variants had no significant association with serum 25-OHD3 levels among postmenopausal women of the Han ethnic group in Beijing. PMID: 25079458
24. CYP2R1 alleles have dosage-dependent effects on vitamin D homeostasis. CYP2R1 mutations cause a novel form of genetic vitamin D deficiency with semidominant inheritance. PMID: 25942481
25. Data indicate that genome-wide significant associations were found both at age 6 and 14 with single nucleotide polymorphisms (SNPs) on chromosome 11p15 in phosphodiesterase 3B, cGMP-inhibited protein PDE3B/cytochrome P-450 CYP2R1 genes. PMID: 25208829
26. In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7) PMID: 24974252
27. The CYP2R1 rs10741657 polymorphism is a novel genetic marker for coronary artery disease. PMID: 25003556
28. genetic association studies in populations in Denmark: Data suggest that an SNP in CYP2R1 (rs10741657) is associated with response to either UVB treatment or vitamin D3 fortification of bread and milk in prevention of vitamin D deficiency in winter. PMID: 25527766
29. The increase in [25(OH)D] attributable to vitamin D3 supplementation may vary according to common genetic differences in vitamin D 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1), and the vitamin D receptor (VDR) genes. PMID: 25070320
30. Data indicate that 1,25(OH)2D3 treatment time-dependently increased Cytochrome P450 2R1 (CYP2R1) expression in oral squamous cell carcinomas. PMID: 24497297
31. genetic differences in the VDR gene may be involved in the development of AITD and the activity of GD, whereas the genetic differences in the GC and CYP2R1 genes may be involved with the intractability of GD. PMID: 25046415
32. Low baseline DNA methylation levels in the promoter region of CYP2R1 is associated with low vitamin D response. PMID: 24128439
33. common polymorphisms in GC and CYP2R1 are associated with serum 25(OH)D concentrations in the Caucasian population and that certain haplotypes may predispose to lower 25(OH)D concentrations in late summer in Denmark. PMID: 24587115
34. Results show that upregulated gene expression of CYP2R1 may lead to misbalance of vitamin D metabolites and may contribute to the pathogenesis of RCC PMID: 24245571
35. Studied whether abnormal endometrial expression of CYP27A1 and/or CYP2R1 may impair VDR-antiproliferative properties in endometrial carcinoma. PMID: 24732451
36. genetic association study in population in Singapore: Data suggest that diet and SNPs in CYP2R1, CYP3A4 (cytochrome P450, subfamily 3A, polypeptide 4), and GC/VDBP (group-specific component) interact to contribute to vitamin D deficiency. PMID: 22583563
37. SNPs in the CYP24A1, CYP2R1, calcium sensing receptor (CASR), vitamin D binding protein (GC), retinoid X receptor-alpha (RXRA) and megalin (LRP2) genes were significantly associated with pancreas cancer risk. PMID: 23826131
38. Data indicate that the same nucleotide polymorphisms (SNPs) genotypes of CYP2R1, GC and DHCR7 that are associated with reduced 25(OH)D3 serum levels were found to be associated with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). PMID: 23734184
39. The GAA haplotype of the CYP2R1 gene (P = 0.026) is associated with susceptibility to rickets. PMID: 24073854
40. In vitro and in vivo studies revealed that CYP2R1 expression in Leydig cells appeared to be hCG dependent. PMID: 23047203
41. Genetic variation in CYP2R1 associated with lower serum 25(OH)D has a decreased risk of aggressive prostate cancer. PMID: 23377224
42. CYP2R1 rs10741657 A>G polymorphism is associated with colon cancer recurrence. PMID: 23793229
43. Finding suggest that GG genotype of CYP2R1 polymorphism and/or CC genotype of CYP27B1 polymorphism increased the risk of developing of type 1 diabetes in Egyptian children. PMID: 23063903
44. genetic association studies in postmenopausal Caucasian women in US: Data suggest that 4 SNPs in CYP2R1 are associated with 25-hydroxyvitamin D in blood (i.e., vitamin D deficiency); vitamin D intake/seasonal sunlight exposure modify these effects. PMID: 23190755
45. Our study is the first to confirm the association of variants in DHCR7 and CYP2R1 with 25(OH)-vitamin D levels in patients with chronic liver diseases. PMID: 22576297
46. Our study found that variant genotypes of single nucleotide polymorphisms in the CYP2R1 gene, rs10766197, rs12794714, rs10741657, rs2060793 and rs1562902, were all significantly associated with plasma 25-hydroxyvitamin D levels. PMID: 22801813
47. CYP2R1 is a major vitamin D 25-hydroxylase that plays a fundamental role in activation of this essential vitamin. PMID: 22855339
48. Study confirms that variation in CYP2R1 is associated with predisposition to autoimmune disease type 1 diabetes. PMID: 21441443
49. We found a lower gene and protein expression of CYP2R1 in samples with hypospermatogenesis and Sertoli-cell-only syndrome. PMID: 21270327
50. Studies indicate that vitamin D synthesis, a two-step process, starts with a 25-hydroxylation primarily by CYP2R1 and a subsequent 1alpha-hydroxylation via CYP27B1. PMID: 20619365

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Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.

Cytochrome P450 family

HGNC: 20580

OMIM: 600081

KEGG: hsa:120227

STRING: 9606.ENSP00000334592

UniGene: Hs.371427