Defective CYP26B1 does not 4-hydroxylate atRA

Stable Identifier
Reaction [transition]
Homo sapiens
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Retinoic acid (RA) is a biologically active analogue of vitamin A (retinol). RA plays an important role in regulating cell growth and differentiation.CYP26A1 and B1 are involved in the metabolic breakdown of RA by 4-hydroxylation. High expression levels of CYP26B1 in the cerebellum and pons of human brain suggests a protective role of specific tissues against retinoid damage (White et al. 2000). Excess exogenous retinoic acid (RA) has teratogenic effects in the limb and craniofacial skeleton. Defects in CYP26B1 can cause radiohumeral fusions with other skeletal and craniofacial anomalies (RHFCA; MIM:614416), a disease characterised by craniofacial malformations and multiple skeletal anomalies. Laue et al. identified homozygosity for a 1088G-T transversion in the CYP26B1 gene, predicting an R363L substitution. The reduction of enzymatic activity for the mutant protein was comparable to that underlying a zebrafish cyp26b1 null allele, indicating that the human mutation constitutes a null allele (Laue et al. 2011).
Literature References
PubMed ID Title Journal Year
10823918 Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism

Everingham, S, Taimi, M, Petkovich, M, Creighton, S, Stangle, W, Ramshaw, H, Jones, G, Zhang, A, Tam, SP, White, JA

Proc Natl Acad Sci U S A 2000
22019272 Craniosynostosis and multiple skeletal anomalies in humans and zebrafish result from a defect in the localized degradation of retinoic acid

Nikkels, PG, Breuning, MH, Kubisch, C, Pogoda, HM, Sutherland-Smith, AJ, Daniel, PB, Hammerschmidt, M, Bloch, W, Morgan, T, Robertson, SP, Wollnik, B, Rachwalski, M, van Haeringen, A, von Ameln, S, Laue, K, Alanay, Y, Sawyer, GM, Gray, MJ

Am. J. Hum. Genet. 2011
Catalyst Activity

retinoic acid 4-hydroxylase activity of CYP26B1 R363L [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of CYP26B1 R363L [endoplasmic reticulum membrane]

Name Identifier Synonyms
craniosynostosis DOID:2340 Premature closure of cranial sutures
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