Defective CYP27B1 does not hydroxylate CDL

Stable Identifier
Reaction [transition]
Homo sapiens
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The second step in vitamin D3 activation requires hydroxylation of 25-hydroxyvitamin D3 (calcidiol) to 1alpha-25-dihydroxyvitamin D3 (calcitriol). This conversion is mediated by 25-hydroxyvitamin D-1alpha hydroxylase (CYP27B1) (Zehnder et al. 2002, Fritsche et al. 2003). Defects in CYP27B1 can cause rickets, vitamin D-dependent 1A (VDDR1A; MIM:264700), a disorder caused by deficiency of the active form of vitamin D (CTL) resulting in defective bone mineralization and clinical features of rickets (Kim 2011). Mutations causing complete loss of function of CYP27B1 include R107H, G125E, R335P, P382S, R389G, R389H and D320Tfs*32 (Kitanaka et al. 1998, Wang et al. 2002, Wang et al. 1998).

Literature References
PubMed ID Title Journal Year
11856765 Synthesis of 1,25-dihydroxyvitamin D(3) by human endothelial cells is regulated by inflammatory cytokines: a novel autocrine determinant of vascular cell adhesion

Zehnder, D, Stewart, PM, Howie, AJ, Bland, R, Wheeler, DC, Hewison, M, Williams, MC, Chana, RS

J Am Soc Nephrol 2002
9837822 Genetics of vitamin D 1alpha-hydroxylase deficiency in 17 families

Miller, WL, Fu, GK, Wang, JT, Burridge, SM, Lin, CJ, Labuda, M, Portale, AA

Am. J. Hum. Genet. 1998
12855575 Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyvitamin D3 by human dendritic cells

Kreutz, M, Andreesen, R, Mondal, K, Fritsche, J, Ehrnsperger, A

Blood 2003
9486994 Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets

Kato, S, Niimi, H, Murayama, A, Okumura, K, Sato, T, Takeyama, K, Tanaka, T, Nogami, M, Yanagisawa, J, Hasegawa, Y, Kitanaka, S

N. Engl. J. Med. 1998
21503197 Vitamin D dependent rickets type I

Kim, CJ

Korean J Pediatr 2011
Catalyst Activity

calcidiol 1-monooxygenase activity of CYP27B1 mutants [mitochondrial outer membrane]

Normal reaction
Functional status

Loss of function of CYP27B1 mutants [mitochondrial outer membrane]

Name Identifier Synonyms
rickets DOID:10609 vitamin D-dependent rickets, active rickets, Rickets, active
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