Defective CYP26C1 does not 4-hydroxylate 9cRA

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. CYP26C1 is involved in the metabolic breakdown of RA by 4-hydroxylation. While CYP26C1 can hydroxylate the trans form, it is unique in hydroxylating the 9-cis isomer of RA (9cRA) (Taimi et al. 2004). Defects in CYP26C1 can cause focal facial dermal dysplasia 4 (FFDD4; MIM:614974), a rare syndrome characterised by facial lesions. Slavotinek et al. identified compound heterozygosity for a 7-bp tandem duplication (844_851dupCCATGCA) in exon 4 of the CYP26C1 gene, causing a frameshift mutation, Q477Hfs*129, and a 1433A-G transition in exon 6 that results in an R478R missense mutation. Both mutations caused loss of CYP26C1 function when transfected into COS-1 cells (Slavotinek et al. 2013).

Literature References
PubMed ID Title Journal Year
23161670 Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1

Tang, PL, Petkovich, M, Lao, R, Chu, C, Yahyavi, M, Nazarenko, I, Mehrotra, P, Frieden, I, Prescott, T, Devriendt, K, Morren, MA, Cordoro, K, Marqueling, AL, Chou, C, Kwok, PY, Slavotinek, AM, Cameron, D, Li, B, Desnick, RJ, Glaser, T

Hum. Mol. Genet. 2013
14532297 A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid

White, J, Taimi, M, Helvig, C, Petkovich, M, Ramshaw, H, Korczak, B, Amad, M, Wisniewski, J

J Biol Chem 2004
Catalyst Activity

retinoic acid 4-hydroxylase activity of CYP26C1 mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of CYP26C1 mutations [endoplasmic reticulum membrane]

Name Identifier Synonyms
skin benign neoplasm DOID:3165 neoplasm of skin (disorder), tumor of the skin, neoplasm of skin by site, skin neoplasm
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