Normal Function
The CYP2R1 gene provides instructions for making an enzyme that is part of the cytochrome P450 family of enzymes. Cytochrome P450 enzymes are involved in the activation or breakdown (metabolism) of many medications and hormones, and they help produce cholesterol, certain hormones, and fats (lipids).
The CYP2R1 enzyme carries out the first of two reactions that are required to convert vitamin D to its active form, which is called calcitriol. Vitamin D can be obtained from food or made in the skin after exposure to the sun or to light from certain other sources, such as tanning beds. When active, vitamin D helps maintain the proper balance of calcium and phosphate in the blood. These minerals strengthen bones and teeth and allow them to develop normally. One of vitamin D's major roles is to help regulate the absorption of calcium and phosphate from the intestines into the bloodstream.
Health Conditions Related to Genetic Changes
Vitamin D-dependent rickets
Certain variants (also called mutations) in the CYP2R1 gene have been found to cause a specific form of vitamin D deficiency called vitamin D-dependent rickets type 1B (VDDR1B). This disorder is characterized by soft, weak bones (rickets) that are prone to fracture and more likely to be misshapen. A common feature of this condition is abnormally curved (bowed) legs, but affected individuals may also have enlargement of the skull, the wrists, and the ends of the ribs.
Certain variants in the CYP2R1 gene cause cells to produce a version of the enzyme that does not function properly. As a result, the conversion of vitamin D to its active form, calcitriol, is disrupted. This impairs the intestinal absorption of calcium and phosphate. Decreased blood levels of calcium and phosphate lead to the weak bones that are seen in affected individuals.
More About This Health ConditionOther Names for This Gene
- vitamin D 25-hydroxylase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Al Mutair AN, Nasrat GH, Russell DW. Mutation of the CYP2R1 vitamin D 25-hydroxylase in a Saudi Arabian family with severe vitamin D deficiency. J Clin Endocrinol Metab. 2012 Oct;97(10):E2022-5. doi: 10.1210/jc.2012-1340. Epub 2012 Aug 1. Citation on PubMed or Free article on PubMed Central
- Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7711-5. doi: 10.1073/pnas.0402490101. Epub 2004 May 5. Citation on PubMed or Free article on PubMed Central
- Gentile C, Chiarelli F. Rickets in Children: An Update. Biomedicines. 2021 Jun 27;9(7):738. doi: 10.3390/biomedicines9070738. Citation on PubMed
- Levine MA. Diagnosis and Management of Vitamin D Dependent Rickets. Front Pediatr. 2020 Jun 12;8:315. doi: 10.3389/fped.2020.00315. eCollection 2020. Citation on PubMed
- Molin A, Wiedemann A, Demers N, Kaufmann M, Do Cao J, Mainard L, Dousset B, Journeau P, Abeguile G, Coudray N, Mittre H, Richard N, Weryha G, Sorlin A, Jones G, Kottler ML, Feillet F. Vitamin D-Dependent Rickets Type 1B (25-Hydroxylase Deficiency): A Rare Condition or a Misdiagnosed Condition? J Bone Miner Res. 2017 Sep;32(9):1893-1899. doi: 10.1002/jbmr.3181. Epub 2017 Jul 13. Citation on PubMed
- Thacher TD, Fischer PR, Singh RJ, Roizen J, Levine MA. CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency. J Clin Endocrinol Metab. 2015 Jul;100(7):E1005-13. doi: 10.1210/jc.2015-1746. Epub 2015 May 5. Citation on PubMed or Free article on PubMed Central
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