Defective CYP2R1 does not 25-hydroxylate vitamin D

Stable Identifier
Reaction [transition]
Homo sapiens
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The first step in vitamin D3 activation requires 25-hydroxylation of vitamin D3 (or vitamin D2), mediated by vitamin D 25-hydroxylase (CYP2R1). Defects in CYP2R1 can cause rickets, vitamin D-dependent 1B (VDDR1B; MIM:600081), a disorder caused by a selective deficiency of the active form of vitamin D (CTL) resulting in defective bone mineralization and clinical features of rickets. The missense mutation L99P can cause VDDR1B (Cheng et al. 2004, Casella et al. 2004). When plasma levels of 25-hydroxyvitamin D3 (calcidiol, CDL) are low, classic symptoms of vitamin D deficiency, including skeletal abnormalities, hypocalcemia, and hypophosphatemia, are observed.

Literature References
PubMed ID Title Journal Year
15128933 Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase

Levine, MA, Bell, NH, Cheng, JB, Mangelsdorf, DJ

Proc Natl Acad Sci U S A 2004
8201479 A possible genetic defect in 25-hydroxylation as a cause of rickets

Holick, MF, Harrison, HE, Chen, TC, Reiner, BJ, Casella, SJ

J. Pediatr. 1994
Catalyst Activity

vitamin D3 25-hydroxylase activity of CYP2R1 L99P [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of CYP2R1 L99P [endoplasmic reticulum membrane]

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