Normal Function
The CYP27B1 gene provides instructions for making an enzyme called 1-alpha-hydroxylase (1α-hydroxylase). This enzyme carries out the second of two reactions to convert vitamin D to its active form, 1,25-dihydroxyvitamin D3, also known as calcitriol. Vitamin D can be acquired from foods in the diet or can be made in the body with the help of sunlight exposure. When active, this vitamin is involved in maintaining the proper balance of several minerals in the body, including calcium and phosphate, which are essential for the normal formation of bones and teeth. One of vitamin D's major roles is to control the absorption of calcium and phosphate from the intestines into the bloodstream. Vitamin D is also involved in several processes unrelated to bone and tooth formation.
Health Conditions Related to Genetic Changes
Vitamin D-dependent rickets
At least 70 mutations in the CYP27B1 gene have been found to cause vitamin D-dependent rickets type 1A (VDDR1A), also known as vitamin D 1α-hydroxylase deficiency. This disorder of bone development is characterized by low levels of calcium (hypocalcemia) and phosphate (hypophosphatemia) in the blood, which lead to soft, weak bones that are prone to fracture. A common feature of this condition is abnormally curved (bowed) legs.
The CYP27B1 gene mutations that cause this condition reduce or eliminate the function of 1α-hydroxylase. As a result, vitamin D does not get converted to its active form and cannot control mineral absorption. The resulting reduction in calcium and phosphate absorption from the intestines into the blood means there is less of these minerals to be deposited in developing bones (bone mineralization), which leads to soft, weak bones and other features of VDDR1A. Hypocalcemia also causes muscle weakness and seizures in some affected individuals.
More About This Health ConditionAutoimmune Addison disease
MedlinePlus Genetics provides information about Autoimmune Addison disease
More About This Health ConditionMultiple sclerosis
MedlinePlus Genetics provides information about Multiple sclerosis
More About This Health ConditionOther Names for This Gene
- 1alpha(OH)ase
- 25 hydroxyvitamin D3-1-alpha hydroxylase
- 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
- 25-OHD-1 alpha-hydroxylase
- CYP1alpha
- CYP27B
- cytochrome p450 27B1
- cytochrome P450 subfamily XXVIIB polypeptide 1
- cytochrome P450, family 27, subfamily B, polypeptide 1
- cytochrome P450C1 alpha
- cytochrome P450VD1-alpha
- P450c1
- VD3 1A hydroxylase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Demir K, Kattan WE, Zou M, Durmaz E, BinEssa H, Nalbantoglu O, Al-Rijjal RA, Meyer B, Ozkan B, Shi Y. Novel CYP27B1 Gene Mutations in Patients with Vitamin D-Dependent Rickets Type 1A. PLoS One. 2015 Jul 1;10(7):e0131376. doi: 10.1371/journal.pone.0131376. eCollection 2015. Citation on PubMed or Free article on PubMed Central
- Durmaz E, Zou M, Al-Rijjal RA, Bircan I, Akcurin S, Meyer B, Shi Y. Clinical and genetic analysis of patients with vitamin D-dependent rickets type 1A. Clin Endocrinol (Oxf). 2012 Sep;77(3):363-9. doi: 10.1111/j.1365-2265.2012.04394.x. Citation on PubMed
- Kim CJ, Kaplan LE, Perwad F, Huang N, Sharma A, Choi Y, Miller WL, Portale AA. Vitamin D 1alpha-hydroxylase gene mutations in patients with 1alpha-hydroxylase deficiency. J Clin Endocrinol Metab. 2007 Aug;92(8):3177-82. doi: 10.1210/jc.2006-2664. Epub 2007 May 8. Citation on PubMed
- Malloy PJ, Feldman D. Genetic disorders and defects in vitamin D action. Rheum Dis Clin North Am. 2012 Feb;38(1):93-106. doi: 10.1016/j.rdc.2012.03.009. Epub 2012 Apr 12. Citation on PubMed
- Nebert DW, Wikvall K, Miller WL. Human cytochromes P450 in health and disease. Philos Trans R Soc Lond B Biol Sci. 2013 Jan 6;368(1612):20120431. doi: 10.1098/rstb.2012.0431. Print 2013 Feb 19. Citation on PubMed or Free article on PubMed Central
- Portale AA, Miller WL. Human 25-hydroxyvitamin D-1alpha-hydroxylase: cloning, mutations, and gene expression. Pediatr Nephrol. 2000 Jul;14(7):620-5. doi: 10.1007/pl00009639. Citation on PubMed
- Ryan JW, Anderson PH, Turner AG, Morris HA. Vitamin D activities and metabolic bone disease. Clin Chim Acta. 2013 Oct 21;425:148-52. doi: 10.1016/j.cca.2013.07.024. Epub 2013 Jul 30. Citation on PubMed
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