[1]
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NUCLEOTIDE SEQUENCE [MRNA] (ALLELE CYP2C19*1A).
TISSUE=Liver;
DOI=10.1021/bi00227a012; PubMed=2009263 [NCBI, ExPASy, EBI, Israel, Japan]
Romkes M.,
Faletto M.B.,
Blaisdell J.A.,
Raucy J.L.,
Goldstein J.A.;
"Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily.";
Biochemistry 30:3247-3255(1991).
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[2]
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ERRATUM, AND SEQUENCE REVISION.
DOI=10.1021/bi00056a025; PubMed=8095407 [NCBI, ExPASy, EBI, Israel, Japan]
Romkes M.,
Faletto M.B.,
Blaisdell J.A.,
Raucy J.L.,
Goldstein J.A.;
Biochemistry 32:1390-1390(1993).
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[3]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-19; ASP-92; ALA-122; HIS-144; ILE-331 AND CYS-410.
Livingston R.J.,
Rieder M.J.,
Chung M.-W.,
Ritchie T.K.,
Olson A.N.,
Nguyen C.P.,
Nguyen D.A.,
Poel C.L.,
Chambers S.W.,
Schackwitz W.S.,
Sherwood J.K.,
Sherwood A.M.,
Leithauser B.J.,
Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
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[4]
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NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature02462; PubMed=15164054 [NCBI, ExPASy, EBI, Israel, Japan]
Deloukas P.,
Earthrowl M.E.,
Grafham D.V.,
Rubenfield M.,
French L.,
Steward C.A.,
Sims S.K.,
Jones M.C.,
Searle S.,
Scott C.,
Howe K.,
Hunt S.E.,
Andrews T.D.,
Gilbert J.G.R.,
Swarbreck D.,
Ashurst J.L.,
Taylor A.,
Battles J.,
Bird C.P., ![]()
Ainscough R.,
Almeida J.P.,
Ashwell R.I.S.,
Ambrose K.D.,
Babbage A.K.,
Bagguley C.L.,
Bailey J.,
Banerjee R.,
Bates K.,
Beasley H.,
Bray-Allen S.,
Brown A.J.,
Brown J.Y.,
Burford D.C.,
Burrill W.,
Burton J.,
Cahill P.,
Camire D.,
Carter N.P.,
Chapman J.C.,
Clark S.Y.,
Clarke G.,
Clee C.M.,
Clegg S.,
Corby N.,
Coulson A.,
Dhami P.,
Dutta I.,
Dunn M.,
Faulkner L.,
Frankish A.,
Frankland J.A.,
Garner P.,
Garnett J.,
Gribble S.,
Griffiths C.,
Grocock R.,
Gustafson E.,
Hammond S.,
Harley J.L.,
Hart E.,
Heath P.D.,
Ho T.P.,
Hopkins B.,
Horne J.,
Howden P.J.,
Huckle E.,
Hynds C.,
Johnson C.,
Johnson D.,
Kana A.,
Kay M.,
Kimberley A.M.,
Kershaw J.K.,
Kokkinaki M.,
Laird G.K.,
Lawlor S.,
Lee H.M.,
Leongamornlert D.A.,
Laird G.,
Lloyd C.,
Lloyd D.M.,
Loveland J.,
Lovell J.,
McLaren S.,
McLay K.E.,
McMurray A.,
Mashreghi-Mohammadi M.,
Matthews L.,
Milne S.,
Nickerson T.,
Nguyen M.,
Overton-Larty E.,
Palmer S.A.,
Pearce A.V.,
Peck A.I.,
Pelan S.,
Phillimore B.,
Porter K.,
Rice C.M.,
Rogosin A.,
Ross M.T.,
Sarafidou T.,
Sehra H.K.,
Shownkeen R.,
Skuce C.D.,
Smith M.,
Standring L.,
Sycamore N.,
Tester J.,
Thorpe A.,
Torcasso W.,
Tracey A.,
Tromans A.,
Tsolas J.,
Wall M.,
Walsh J.,
Wang H.,
Weinstock K.,
West A.P.,
Willey D.L.,
Whitehead S.L.,
Wilming L.,
Wray P.W.,
Young L.,
Chen Y.,
Lovering R.C.,
Moschonas N.K.,
Siebert R.,
Fechtel K.,
Bentley D.,
Durbin R.M.,
Hubbard T.,
Doucette-Stamm L.,
Beck S.,
Smith D.R.,
Rogers J.;
"The DNA sequence and comparative analysis of human chromosome 10.";
Nature 429:375-381(2004).
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[5]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-160 AND 274-490, AND VARIANT ILE-331.
de Morais S.M.F.,
Blaisdell J.A.;
"Gene structure, upstream region and allelic variants of cyp2c19, the s-mephenytoin hydroxylase.";
Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
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[6]
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PROTEIN SEQUENCE OF 1-16.
TISSUE=Liver;
DOI=10.1006/abbi.1993.1506; PubMed=8215410 [NCBI, ExPASy, EBI, Israel, Japan]
Wrighton S.A.,
Stevens J.C.,
Becker G.W.,
VandenBranden M.;
"Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4'-hydroxylation.";
Arch. Biochem. Biophys. 306:240-245(1993).
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[7]
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CHARACTERIZATION.
DOI=10.1124/dmd.30.5.602; PubMed=11950794 [NCBI, ExPASy, EBI, Israel, Japan]
Miyazawa M.,
Shindo M.,
Shimada T.;
"Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes.";
Drug Metab. Dispos. 30:602-607(2002).
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[8]
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INVOLVEMENT IN POOR DRUG METABOLISM, AND IDENTIFICATION OF ALLELE CYP2C19*2A.
PubMed=8195181 [NCBI, ExPASy, EBI, Israel, Japan]
de Morais S.M.F.,
Wilkinson G.R.,
Blaisdell J.,
Nakamura K.,
Meyer U.A.,
Goldstein J.A.;
"The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans.";
J. Biol. Chem. 269:15419-15422(1994).
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[9]
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INVOLVEMENT IN POOR DRUG METABOLISM, AND IDENTIFICATION OF ALLELE CYP2C19*3A.
PubMed=7969038 [NCBI, ExPASy, EBI, Israel, Japan]
De Morais S.M.F.,
Wilkinson G.R.,
Blaisdell J.,
Meyer U.A.,
Nakamura K.,
Goldstein J.A.;
"Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese.";
Mol. Pharmacol. 46:594-598(1994).
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[10]
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VARIANT TRP-433.
PubMed=9103550 [NCBI, ExPASy, EBI, Israel, Japan]
Xiao Z.S.,
Goldstein J.A.,
Xie H.G.,
Blaisdell J.,
Wang W.,
Jiang C.H.,
Yan F.X.,
He N.,
Huang S.L.,
Xu Z.H.,
Zhou H.H.;
"Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele.";
J. Pharmacol. Exp. Ther. 281:604-609(1997).
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[11]
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VARIANTS ASP-92 AND GLN-132.
PubMed=9732415 [NCBI, ExPASy, EBI, Israel, Japan]
Ibeanu G.C.,
Goldstein J.A.,
Meyer U.A.,
Benhamou S.,
Bouchardy C.,
Dayer P.,
Ghanayem B.I.,
Blaisdell J.;
"Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin.";
J. Pharmacol. Exp. Ther. 286:1490-1495(1998).
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[12]
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VARIANT TRP-433.
PubMed=10022751 [NCBI, ExPASy, EBI, Israel, Japan]
Ibeanu G.C.,
Blaisdell J.,
Ghanayem B.I.,
Beyeler C.,
Benhamou S.,
Bouchardy C.,
Wilkinson G.R.,
Dayer P.,
Daly A.K.,
Goldstein J.A.;
"An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians.";
Pharmacogenetics 8:129-135(1998).
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[13]
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VARIANT ARG-120.
PubMed=10411572 [NCBI, ExPASy, EBI, Israel, Japan]
Ibeanu G.C.,
Blaisdell J.,
Ferguson R.J.,
Ghanayem B.I.,
Brosen K.,
Benhamou S.,
Bouchardy C.,
Wilkinson G.R.,
Dayer P.,
Goldstein J.A.;
"A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin.";
J. Pharmacol. Exp. Ther. 290:635-640(1999).
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[14]
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VARIANTS PRO-17; LEU-19; HIS-144; HIS-150; LEU-227 AND CYS-410.
DOI=10.1097/00008571-200212000-00004; PubMed=12464799 [NCBI, ExPASy, EBI, Israel, Japan]
Blaisdell J.,
Mohrenweiser H.,
Jackson J.,
Ferguson S.,
Coulter S.,
Chanas B.,
Xi T.,
Ghanayem B.,
Goldstein J.A.;
"Identification and functional characterization of new potentially defective alleles of human CYP2C19.";
Pharmacogenetics 12:703-711(2002).
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[15]
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VARIANT CYS-442.
DOI=10.2133/dmpk.19.236; PubMed=15499191 [NCBI, ExPASy, EBI, Israel, Japan]
Morita J.,
Kobayashi K.,
Wanibuchi A.,
Kimura M.,
Irie S.,
Ishizaki T.,
Chiba K.;
"A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese subject with lowered capacity of mephobarbital 4'-hydroxylation.";
Drug Metab. Pharmacokinet. 19:236-238(2004).
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[16]
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VARIANTS THR-74; HIS-144; LEU-168 AND ILE-331.
DOI=10.1517/14622416.5.7.895; PubMed=15469410 [NCBI, ExPASy, EBI, Israel, Japan]
Solus J.F.,
Arietta B.J.,
Harris J.R.,
Sexton D.P.,
Steward J.Q.,
McMunn C.,
Ihrie P.,
Mehall J.M.,
Edwards T.L.,
Dawson E.P.;
"Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population.";
Pharmacogenomics 5:895-931(2004).
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[17]
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VARIANTS GLY-51; PRO-161; HIS-329 AND ILE-331.
DOI=10.2133/dmpk.20.300; PubMed=16141610 [NCBI, ExPASy, EBI, Israel, Japan]
Fukushima-Uesaka H.,
Saito Y.,
Maekawa K.,
Ozawa S.,
Hasegawa R.,
Kajio H.,
Kuzuya N.,
Yasuda K.,
Kawamoto M.,
Kamatani N.,
Suzuki K.,
Yanagawa T.,
Tohkin M.,
Sawada J.;
"Genetic variations and haplotypes of CYP2C19 in a Japanese population.";
Drug Metab. Pharmacokinet. 20:300-307(2005).
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- FUNCTION: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
- CATALYTIC ACTIVITY: +-(R)-limonene + NADPH + O2 = (+)-trans-carveol + NADP+ + H2O.
- CATALYTIC ACTIVITY: --(S)-limonene + NADPH + O2 = (-)-trans-carveol + NADP+ + H2O.
- CATALYTIC ACTIVITY: --(S)-limonene + NADPH + O2 = (-)-perillyl alcohol + NADP+ + H2O.
- COFACTOR: Heme group (By similarity).
- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
- INDUCTION: P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.
- POLYMORPHISM: Genetic variation in CYP2C19 is responsible for poor drug metabolism [MIM:609535]. Individuals can be characterized as either extensive metabolizers (EM) or poor metabolizers (PM). The PM phenotype is inherited in an autosomal recessive manner, with the EM phenotype comprising both homozygous dominant and heteroyzgote genotypes. There are marked interracial differences in the frequency of this polymorphism. Poor metabolizers represent 2-5% of Caucasians, 13-23% of Asian populations, and as many as 38-79% of individuals of some of the islands of Polynesia and Micronesia. Different alleles of CYP2C19 are known: CYP2C19*1A CYP2C19*1B, CYP2C19*1C, CYP2C19*2A (CYP2C19m1 or CYP2C19m1A), CYP2C19*2B (CYP2C19m1B), CYP2C19*2C (CYP2C19*21), CYP2C19*3A (CYP2C19m2), CYP2C19*3B (CYP2C19*20), CYP2C19*4 (CYP2C19m3), CYP2C19*5A (CYP2C19m4), CYP2C19*5B, CYP2C19*6, CYP2C19*7, CYP2C19*8, CYP2C19*9, CYP2C19*10, CYP2C19*11 CYP2C19*12, CYP2C19*13, CYP2C19*14 CYP2C19*15, CYP2C19*16, CYP2C19*18, CYP2C19*19. Defective CYP2C19*2 and CYP2C19*3 alleles are characterized by a splice mutation and a stop codon, respectively, and account for most of the PM alleles. The sequence shown is that of allele CYP2C19*1B.
- SIMILARITY: Belongs to the cytochrome P450 family.
- CAUTION: P450-254C was originally listed as a separate gene (CYP2C17). Resequencing demonstrated that it is not a separate gene, but a chimera. The 5'-portion corresponds to a partial 2C18 clone, and the 3'-portion corresponds to a partial 2C19 clone.
- WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee; Note=CYP2C19 alleles; URL="http://www.cypalleles.ki.se/cyp2c19.htm";.
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