Defective CYP26C1 does not 4-hydroxylate 9cRA

Stable Identifier
R-HSA-5602050
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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
14532297 A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid

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

J Biol Chem 2004
23161670 Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1

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

Hum. Mol. Genet. 2013
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
retinoic acid 4-hydroxylase activity of CYP26C1 mutants [endoplasmic reticulum membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
skin benign neoplasm 3165 neoplasm of skin (disorder), tumor of the skin, neoplasm of skin by site, skin neoplasm
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