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Gene Review

CYP2C18  -  cytochrome P450, family 2, subfamily C,...

Homo sapiens

Synonyms: CPCI, CYP2C, CYP2C17, CYPIIC18, Cytochrome P450 2C18, ...
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Disease relevance of CYP2C18

  • Cytochrome p450 2C (CYP2C) in ischemic heart injury and vascular dysfunction [1].

Psychiatry related information on CYP2C18

  • Fifty adults with CP and chronic pain were interviewed to assess pain experience, the interference of pain on activities (BPI), depressive symptoms (CES-D), and coping strategies used for the pain (CSQ and CPCI) [2].

High impact information on CYP2C18

  • The cytochrome P-450 2C18 gene was found by reverse transcription-PCR to represent the most abundantly expressed gene of the P-450 2C subfamily in human epidermis [3].
  • Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis [3].
  • These data clearly implicate CYP3A in the formation of metabolite M4 and CYP2C in the synthesis of metabolite M5 [4].
  • Correlation between CYP2C content or diazepam demethylation and the synthesis of metabolite M5 was highly positive [4].
  • Reverse transcription-PCR analysis in human epidermis, using primers from CYP2C18 and CYP2C19, revealed products containing combinations between canonically defined exons of these two genes [5].

Biological context of CYP2C18


Anatomical context of CYP2C18


Associations of CYP2C18 with chemical compounds

  • CYP2C18 had the highest in vitro intrinsic clearance/catalytic efficiency (apparent Vmax/Km) in cyclophosphamide and ifosfamide activation, followed by 2C19 > 2C9 approximately 2C8 [14].
  • CYP2A6, 2B6, 2C8, 2C9, 2C19, and 2D6 each showed a varying degree of low catalytic activity for estrogen 2-hydroxylation, whereas CYP2C18 and CYP2E1 did not show any detectable estrogen-hydroxylating activity [15].
  • Although CYP2C18 is an efficient methoxychlor demethylase, its expression in liver is reportedly low or absent, suggesting a negligible role for this enzyme in methoxychlor metabolism [16].
  • All of the tested CYPs, except CYP2A6 and CYP2C18, metabolized ethanol into significant amounts of acetaldehyde and displayed K(m) values around 10mM [17].
  • In conclusion, our results show that enzymes of the CYP2C subfamily are mainly involved in verapamil O-demethylation [18].

Other interactions of CYP2C18


Analytical, diagnostic and therapeutic context of CYP2C18

  • Rapid amplification of cDNA ends (RACE) and PCR amplifications of human liver cDNA revealed the presence of several intergenic species containing the CYP2C18 exon 1-like sequence spliced to different combinations of exonic and intronic sequences from the CYP2C9 gene [8].
  • METHODS: The human CYP2C18 cDNA was amplified with reverse transcription-polymerase chain reaction (RT-PCR) from total RNAs extracted from human liver and cloned into pGEM-T vector [11].
  • The enzyme activity of CYP2C18 to oxidate tolbutamide in postmitochondrial supernate (S9) fraction was determined by HPLC [23].
  • Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C51 [24].
  • Initial research has supported the reliability and validity of the CPCI [25].


  1. Cytochrome p450 2C (CYP2C) in ischemic heart injury and vascular dysfunction. Chehal, M.K., Granville, D.J. Can. J. Physiol. Pharmacol. (2006) [Pubmed]
  2. Pain in cerebral palsy: the relation of coping strategies to adjustment. Engel, J.M., Schwartz, L., Jensen, M.P., Johnson, D.R. Pain (2000) [Pubmed]
  3. Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis. Zaphiropoulos, P.G. Mol. Cell. Biol. (1997) [Pubmed]
  4. Taxol metabolism by human liver microsomes: identification of cytochrome P450 isozymes involved in its biotransformation. Cresteil, T., Monsarrat, B., Alvinerie, P., Tréluyer, J.M., Vieira, I., Wright, M. Cancer Res. (1994) [Pubmed]
  5. RNA molecules containing exons originating from different members of the cytochrome P450 2C gene subfamily (CYP2C) in human epidermis and liver. Zaphiropoulos, P.G. Nucleic Acids Res. (1999) [Pubmed]
  6. The human CYP2C locus: a prototype for intergenic and exon repetition splicing events. Finta, C., Zaphiropoulos, P.G. Genomics (2000) [Pubmed]
  7. Gene structure and upstream regulatory regions of human CYP2C9 and CYP2C18. de Morais, S.M., Schweikl, H., Blaisdell, J., Goldstein, J.A. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  8. Intergenic transcripts containing a novel human cytochrome P450 2C exon 1 spliced to sequences from the CYP2C9 gene. Warner, S.C., Finta, C., Zaphiropoulos, P.G. Mol. Biol. Evol. (2001) [Pubmed]
  9. Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. Klose, T.S., Blaisdell, J.A., Goldstein, J.A. J. Biochem. Mol. Toxicol. (1999) [Pubmed]
  10. In vitro metabolism of tributyltin and triphenyltin by human cytochrome P-450 isoforms. Ohhira, S., Enomoto, M., Matsui, H. Toxicology (2006) [Pubmed]
  11. Establishment of a transgenic cell line stably expressing human cytochrome P450 2C18 and identification of a CYP2C18 clone with exon 5 missing. Zhu-Ge, J., Yu, Y.N., Qian, Y.L., Li, X. World J. Gastroenterol. (2002) [Pubmed]
  12. P450 CYP2C epoxygenase and CYP4A {omega}-hydroxylase mediate ciprofibrate-induced PPAR{alpha}-dependent peroxisomal proliferation. Gatica, A., Aguilera, M.C., Contador, D., Loyola, G., Pinto, C.O., Amigo, L., Tichauer, J.E., Zanlungo, S., Bronfman, M. J. Lipid Res. (2007) [Pubmed]
  13. Midazolam and triazolam biotransformation in mouse and human liver microsomes: relative contribution of CYP3A and CYP2C isoforms. Perloff, M.D., von Moltke, L.L., Court, M.H., Kotegawa, T., Shader, R.I., Greenblatt, D.J. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  14. Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Chang, T.K., Yu, L., Goldstein, J.A., Waxman, D.J. Pharmacogenetics (1997) [Pubmed]
  15. Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Lee, A.J., Cai, M.X., Thomas, P.E., Conney, A.H., Zhu, B.T. Endocrinology (2003) [Pubmed]
  16. Human cytochrome P450-catalyzed conversion of the proestrogenic pesticide methoxychlor into an estrogen. Role of CYP2C19 and CYP1A2 in O-demethylation. Stresser, D.M., Kupfer, D. Drug Metab. Dispos. (1998) [Pubmed]
  17. Ethanol oxidation into acetaldehyde by 16 recombinant human cytochrome P450 isoforms: Role of CYP2C isoforms in human liver microsomes. Hamitouche, S., Poupon, J., Dreano, Y., Amet, Y., Lucas, D. Toxicol. Lett. (2006) [Pubmed]
  18. Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Busse, D., Cosme, J., Beaune, P., Kroemer, H.K., Eichelbaum, M. Naunyn Schmiedebergs Arch. Pharmacol. (1995) [Pubmed]
  19. A review of developmental aspects of cytochrome P450. Oesterheld, J.R. Journal of child and adolescent psychopharmacology. (1998) [Pubmed]
  20. Polymerase chain reaction-directed identification, cloning, and quantification of human CYP2C18 mRNA. Furuya, H., Meyer, U.A., Gelboin, H.V., Gonzalez, F.J. Mol. Pharmacol. (1991) [Pubmed]
  21. [O-methyl 14C]naproxen O-demethylase activity in human liver microsomes: evidence for the involvement of cytochrome P4501A2 and P4502C9/10. Rodrigues, A.D., Kukulka, M.J., Roberts, E.M., Ouellet, D., Rodgers, T.R. Drug Metab. Dispos. (1996) [Pubmed]
  22. Pharmacogenetics and drug metabolism of newer antidepressant agents. DeVane, C.L. The Journal of clinical psychiatry. (1994) [Pubmed]
  23. Enzyme activity analysis of CYP2C18 with exon 5 skipped. Zhu-Ge, J., Yu, Y.N. Acta Pharmacol. Sin. (2004) [Pubmed]
  24. Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C51. Richardson, T.H., Griffin, K.J., Jung, F., Raucy, J.L., Johnson, E.F. Arch. Biochem. Biophys. (1997) [Pubmed]
  25. The Chronic Pain Coping Inventory-42: reliability and validity. Romano, J.M., Jensen, M.P., Turner, J.A. Pain (2003) [Pubmed]
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