Affinage

CYP2C19

Cytochrome P450 2C19 · UniProt P33261

Length
490 aa
Mass
55.9 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYP2C19 is a hepatic cytochrome P450 monooxygenase that performs stereoselective oxidative metabolism of a broad range of clinical drugs and endogenous substrates (PMID:15288804, PMID:26899628). Its transcription is governed by a network of nuclear receptors acting at defined promoter elements: CAR and PXR bind a CAR-RE (-1891/-1876) and the glucocorticoid receptor binds a GRE (-1750/-1736) to upregulate expression, while ERα binds an ERE half-site (-151/-147) to mediate ligand-dependent repression (PMID:12869636, PMID:20675569); PXR activation also underlies xenobiotic induction by agents such as dicloxacillin (PMID:29105855). Expression is further constrained post-transcriptionally by direct binding of hsa-miR-29a-3p to the transcript coding region (PMID:26296572), and the cis-regulatory *17 allele increases hepatic mRNA roughly two- to threefold (PMID:23412869). Catalytically, CYP2C19 hydroxylates S-mephenytoin, omeprazole (5-hydroxylation), R-mephobarbital, tivantinib, and clopidogrel, and bioactivates compounds including rhein to a hepatotoxic reactive epoxide (PMID:11501187, PMID:15284537, PMID:26899628, PMID:24945780, PMID:25815638); it also possesses minor capacity for progesterone 21-hydroxylation (PMID:18957504). Active-site geometry is sensitive to inhibitor stereochemistry and is distinguished from the closely related CYP2C9 by substrate recognition site residues, particularly SRS4, that determine both protein stability and substrate specificity (PMID:15288804, PMID:39319420). Loss-of-function and altered-function missense variants, including *10, *18, *19, reduce catalytic activity or protein abundance, while a substantial fraction of genomic missense variants destabilize the protein (PMID:17455109, PMID:24945780, PMID:39319420, PMID:32004414). Beyond drug metabolism, CYP2C19 is expressed in fetal brain and, in a humanized transgenic model, modulates hippocampal BDNF and serotonin signaling (PMID:27895323).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 Medium

    Establishing which P450 isoform drives a clinically important metabolic reaction was needed to assign drug-handling responsibility; this defined CYP2C19 as the principal omeprazole 5-hydroxylase distinct from CYP3A4-mediated sulfoxidation.

    Evidence Antibody inhibition, immunoquantification, and correlation analysis in human liver microsomes

    PMID:11501187

    Open questions at the time
    • Does not resolve atomic active-site determinants of regioselectivity
    • Population-specific to Chinese liver samples
  2. 2003 High

    How CYP2C19 transcription is controlled was unknown; identification of a CAR/PXR-binding CAR-RE and a GR-responsive GRE in the promoter established receptor-mediated transcriptional induction.

    Evidence EMSA, reporter assays, and site-directed mutagenesis in HepG2 cells with endogenous mRNA measurement

    PMID:12869636

    Open questions at the time
    • Does not quantify relative contribution of each receptor in vivo
    • Endogenous chromatin occupancy not tested by ChIP
  3. 2003 Medium

    Whether CYP2C19 is developmentally regulated like its paralog was open; ontogeny profiling showed a distinct expression trajectory from fetal life to adulthood, implying separate developmental control from CYP2C9.

    Evidence Western blotting and mephenytoin 4'-hydroxylation activity across 237 liver microsomal samples

    PMID:14634042

    Open questions at the time
    • Regulatory factors driving the developmental pattern not identified
    • Brain ontogeny not assessed
  4. 2004 High

    The structural basis of CYP2C19 substrate/inhibitor selectivity was undefined; inhibitor stereochemistry studies and CoMFA modeling defined an active-site geometry that orients N-3 substituents and distinguishes CYP2C19 from CYP2C9.

    Evidence Recombinant enzyme competitive inhibition kinetics, metabolite identification, and CoMFA modeling

    PMID:15288804

    Open questions at the time
    • No experimental crystal structure presented
    • Model derived from limited inhibitor chemotypes
  5. 2004 Medium

    Assigning the in vivo stereoselective metabolism of mephobarbital clarified CYP2C19's enantiomer-specific role; PM genotypes showed dramatically elevated R-mephobarbital exposure while S-conversion was genotype-independent.

    Evidence Controlled human PK study with CYP2C19 genotyping and plasma/urine metabolite measurement

    PMID:15284537

    Open questions at the time
    • Mechanistic basis of enantiomer discrimination not structurally resolved
    • Limited to one substrate
  6. 2007 Medium

    Defining the functional consequences of natural variants was needed for pharmacogenetic interpretation; kinetic characterization showed *19 reduces substrate affinity for S-mephenytoin while *18 is functionally neutral.

    Evidence Heterologous yeast expression and Km/Vmax kinetics for S-mephenytoin 4'-hydroxylation

    PMID:17455109

    Open questions at the time
    • Single substrate tested
    • Yeast expression may not reflect human hepatic context
  7. 2007 Medium

    Whether CYP2C19 contributes meaningfully to midazolam metabolism was tested; recombinant enzyme catalyzed 1'-hydroxylation but inhibitor studies showed its hepatic contribution is minor relative to CYP3A4/5.

    Evidence Recombinant enzyme kinetics with selective inhibitor and HLM correlation analysis

    PMID:17614006

    Open questions at the time
    • Does not address physiological relevance in special populations
    • Single-lab HLM correlation
  8. 2008 High

    Whether CYP2C19 acts on endogenous steroids was unresolved; reconstituted assays showed it can 21-hydroxylate progesterone but not 17-hydroxyprogesterone, defining a restricted endogenous substrate capacity.

    Evidence Reconstituted in vitro assay with purified CYP2C19 and POR, radiolabeled substrate kinetics

    PMID:18957504

    Open questions at the time
    • Physiological significance of progesterone 21-hydroxylation in vivo unknown
    • Activity is only ~17% of dedicated P450c21
  9. 2010 High

    How estrogen suppresses CYP2C19 was unknown; an ERE half-site mediating ERα-dependent transcriptional repression was identified, establishing negative hormonal regulation distinct from direct enzyme inhibition.

    Evidence Luciferase reporter, EMSA, ChIP, mutagenesis, and RT-PCR in human hepatocytes

    PMID:20675569

    Open questions at the time
    • Coregulator complexes mediating repression not identified
    • In vivo physiological estrogen effect not quantified
  10. 2013 Medium

    The molecular mechanism of the increased-function *17 allele was clarified; allelic mRNA quantification confirmed *17 acts in cis to elevate transcription and revealed additional regulatory variants.

    Evidence qRT-PCR, allelic mRNA expression ratio, and enzyme activity in human liver samples

    PMID:23412869

    Open questions at the time
    • Specific transcription factor altered by *17 not pinpointed
    • Additional regulatory variants uncharacterized
  11. 2013 Medium

    Whether drug induction of CYP2C19 is genotype-dependent was tested; efavirenz increased omeprazole 5-hydroxylation differentially across CYP2C19 genotypes in a non-stereoselective manner.

    Evidence Controlled clinical PK study with genotype stratification and LC-MS/MS enantiomer measurement

    PMID:23629159

    Open questions at the time
    • Receptor mediating efavirenz induction not directly identified
    • CYP2B6 contribution excluded only by genotype association
  12. 2014 Medium

    Post-transcriptional control of CYP2C19 was undefined; direct miRNA-transcript binding established hsa-miR-29a-3p as a suppressor of expression in cells and human liver.

    Evidence In silico analysis, RNA EMSA, and qRT-PCR in HepaRG cells and human liver tissue

    PMID:26296572

    Open questions at the time
    • Binding within coding region rather than canonical 3'UTR not mechanistically dissected
    • In vivo loss-of-miRNA validation absent
  13. 2014 Medium

    Several findings extended substrate scope and variant impact, defining CYP2C19 bioactivation and stereoselective and loss-of-function behavior across drugs.

    Evidence Recombinant enzyme assays for clopidogrel/2-oxo-clopidogrel (*10), rhein bioactivation with GSH trapping and hepatocyte rescue, and NHP-ortholog SRS mutagenesis with docking

    PMID:24945780 PMID:25036290 PMID:25815638

    Open questions at the time
    • Rhein hepatotoxicity demonstrated in rat hepatocytes, not human in vivo
    • NHP-ortholog substitutions may not map directly to human variants
  14. 2016 Medium

    Whether CYP2C19 has a role beyond drug metabolism was tested; humanized transgenic mice linked CYP2C19 expression to hippocampal BDNF and serotonin signaling, implicating it in neurodevelopment.

    Evidence 2C19TG transgenic mouse behavioral and biochemical assays including BDNF, serotonin metabolites, and ERK1/2/GSK3β phosphorylation

    PMID:27895323

    Open questions at the time
    • Endogenous neural substrate of CYP2C19 not identified
    • Transgene overexpression may not reflect physiological brain levels
  15. 2020 High

    The proteome-wide stability consequences of CYP2C19 variation were unknown; deep mutational scanning quantified abundance of thousands of variants and localized SRS4 as a CYP2C19-specific determinant of stability and substrate specificity versus CYP2C9.

    Evidence VAMP-seq deep mutational scanning of protein abundance in cultured human cells

    PMID:32004414 PMID:39319420

    Open questions at the time
    • Abundance does not directly measure catalytic competence
    • Functional consequences for specific clinical substrates not assayed per variant
  16. 2024 Medium

    Variant effects on a newer therapeutic substrate were profiled; recombinant CYP2C19 variant systems showed bidirectional effects on tofacitinib metabolism and characterized inhibitor kinetics.

    Evidence Recombinant CYP2C19/CYP3A4 variant expression with UPLC-MS/MS metabolite quantification and inhibitor kinetics

    PMID:38719708

    Open questions at the time
    • Clinical PK consequences not measured
    • Single-lab recombinant system

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether CYP2C19 functions as a physiologically significant arachidonic acid epoxygenase and how its endogenous (steroid and lipid) substrate activities integrate with its neurodevelopmental role remains unresolved.
  • EET production inferred only from serum DHET in PM patients without a direct enzyme assay (idx 21)
  • Endogenous brain substrate undefined
  • No structural model linking active-site geometry to endogenous lipid metabolism

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0140096 catalytic activity, acting on a protein 5
Localization
GO:0005783 endoplasmic reticulum 1
Partners
POR

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 The CYP2C19 promoter contains a constitutive androstane receptor/pregnane X receptor binding site (CAR-RE; -1891/-1876 bp) and a glucocorticoid-responsive element (GRE; -1750/-1736 bp). Gel-shift assays showed CAR-RE binds CAR and PXR; cotransfection with hCAR, mCAR, or hPXR in HepG2 cells upregulated CYP2C19 promoter transcription, and mutation of the -1891-bp CAR-RE abolished this upregulation. Dexamethasone activated CYP2C19 promoter constructs only when cotransfected glucocorticoid receptor (GR) was present, and mutation of the GRE abolished dexamethasone activation. Gel-shift (EMSA), cotransfection/reporter assays in HepG2 cells, site-directed mutagenesis, endogenous mRNA measurement Molecular pharmacology High 12869636
2010 Estrogen receptor α (ERα) downregulates CYP2C19 expression via a newly identified ERE half-site at position -151/-147 in the CYP2C19 promoter. EMSA and chromatin immunoprecipitation confirmed ERα binding to this element; mutations in the ERE half-site significantly inhibited ligand-dependent repression. Treatment of human hepatocytes with 17β-estradiol or 17α-ethinylestradiol significantly suppressed CYP2C19 transcription. Competitive inhibition of CYP2C19 enzymatic activity by these steroids required much higher concentrations than those needed for transcriptional inhibition, indicating the primary mechanism is transcriptional. Luciferase reporter assay, EMSA, chromatin immunoprecipitation (ChIP), site-directed mutagenesis, RT-PCR in human hepatocytes, enzymatic inhibition assays in stable HEK293-CYP2C19 cells Molecular pharmacology High 20675569
2015 hsa-miR-29a-3p directly binds the CYP2C19 transcript coding region (predicted hybrid stability -23.3 kcal/mol) and suppresses CYP2C19 expression. RNA EMSA confirmed direct miRNA-mRNA binding; chemically induced upregulation of hsa-miR-29a-3p in HepaRG cells inversely correlated with CYP2C19 expression; inverse correlations between miR-29a-3p levels and CYP2C19 mRNA were also observed in human liver tissue samples. In silico analysis, RNA electrophoretic mobility shift assay (EMSA), qRT-PCR in HepaRG cells and human liver tissue Biochemical pharmacology Medium 26296572
2008 CYP2C19 (bacterially expressed, purified) can 21-hydroxylate progesterone with a Vmax/Km ~17% of that of the dedicated adrenal 21-hydroxylase P450c21, and a Km of ~11 µM. CYP2C19 cannot 21-hydroxylate 17-hydroxyprogesterone. The common P450 oxidoreductase (POR) variant A503V did not substantially alter these activities. Reconstituted in vitro enzyme assay with bacterially expressed N-terminally modified C-His-tagged CYP2C19 and wild-type or A503V POR; radiolabeled substrate, Km/Vmax measurement The Journal of clinical endocrinology and metabolism High 18957504
2004 Active-site characterization of CYP2C19 using N-3 alkyl-substituted phenytoin, nirvanol, and barbiturate derivatives showed all are competitive inhibitors. Inhibitor stereochemistry is an important determinant of potency toward CYP2C19 (but not CYP2C9). (S)-(+)-N-3-benzylnirvanol and (R)-(-)-N-3-benzylphenobarbital are highly potent and selective CYP2C19 inhibitors (Ki < 250 nM). CYP2C19 preferentially orients N-3 substituents away from the active oxygen species (metabolizes at C-5 phenyl substituents). A validated CoMFA model for CYP2C19 active-site geometry was developed. Recombinant enzyme competitive inhibition assays (Ki determination), metabolite identification, CoMFA modeling Archives of biochemistry and biophysics High 15288804
2014 CYP2C19 activates rhein (rhubarb anthraquinone) to a reactive epoxide intermediate, as demonstrated by IC50 shift experiments (IC50 shift value 1.989). CYP2C19 is the primary metabolic enzyme for rhein. In primary rat hepatocytes, co-addition of a CYP2C19 inhibitor with rhein restored mitochondrial membrane potential and reduced AST levels, indicating CYP2C19-mediated bioactivation drives rhein hepatotoxicity. IC50 shift assay, GSH-trapping (reactive metabolite identification), primary rat hepatocyte cytotoxicity assay, mitochondrial membrane potential measurement, AST assay Xenobiotica Medium 25815638
2007 CYP2C19 variant *19 (Ser51Gly/Ile331Val) expressed in yeast showed a 3-fold higher Km for S-mephenytoin 4'-hydroxylation compared to wild-type (CYP2C19.1B), with Vmax/Km reduced to 29–47% of wild-type, indicating decreased substrate affinity. CYP2C19 variant *18 (Arg329His/Ile331Val) showed no significant change in Km, Vmax, or Vmax/Km. Heterologous expression in yeast, enzyme kinetics (Km, Vmax determination) for S-mephenytoin 4'-hydroxylation Xenobiotica Medium 17455109
2007 CYP2C19 (recombinant) can catalyze midazolam 1'-hydroxylation with a Michaelis-Menten kinetic profile, and this activity is inhibited by the selective CYP2C19 inhibitor (+)-N-3-benzylnirvanol and by S-mephenytoin. However, the contribution of CYP2C19 to midazolam 1'-hydroxylation in human liver microsomes is minor compared to CYP3A4/5, as addition of (+)-N-3-benzylnirvanol did not change intrinsic clearance in HLM preparations. Recombinant CYP2C19 enzyme assay, selective inhibitor studies, correlation analysis in human liver microsomes Xenobiotica Medium 17614006
2016 CYP2C19 catalyzes stereoselective hydroxylation of tivantinib: CYP2C19 forms M5 (one hydroxylated metabolite stereoisomer) but not M4 (its stereoisomer), whereas CYP3A4/5 catalyzes both. CYP2C19 and CYP3A4/5 are the primary isoforms for tivantinib elimination. In vitro metabolism using recombinant CYP isoforms and human liver microsomes; metabolite identification and quantification Xenobiotica Medium 26899628
2014 The CYP2C19*10 variant protein (expressed recombinantly) shows significantly decreased catalytic activity in the biotransformation of clopidogrel and its intermediate 2-oxo-clopidogrel compared to wild-type CYP2C19.1B, establishing *10 as a partial loss-of-function allele for clopidogrel bioactivation. Recombinant protein expression, enzymatic activity assay for clopidogrel and 2-oxo-clopidogrel metabolism Pharmacogenetics and genomics Medium 24945780
2014 CYP2C19 variants (cynomolgus macaque CYP2C19 with p.Phe100Asn, p.Ala103Val, p.Ile112Leu substitutions in substrate recognition sites) showed substantially reduced catalytic activity for flurbiprofen 4'-hydroxylation, omeprazole 5-hydroxylation, and R-/S-warfarin 7-hydroxylation compared to wild-type. Kinetic analysis of Ala103Val showed it diminishes homotropic cooperativity of CYP2C19 with R-warfarin, yielding low metabolic capacity. Site-directed mutagenesis, recombinant protein expression, metabolic assays, kinetic analysis, docking simulation Biochemical pharmacology Medium 25036290
2000 Omeprazole 5-hydroxylation in Chinese liver microsomes is mediated primarily by CYP2C19 (inhibited by anti-CYP2C8/9/19 antibody; activity correlates with S-mephenytoin 4'-hydroxylation and CYP2C19 protein content), while omeprazole sulfoxidation is mediated primarily by CYP3A4 (anti-CYP3A4 antibody abolished >87% of this activity; correlated with CYP3A4 content). HPLC metabolite quantification, monoclonal antibody inhibition, Western blot, correlation analysis in human liver microsomes Acta pharmacologica Sinica Medium 11501187
2003 CYP2C19 protein and catalytic activity (S-mephenytoin 4'-hydroxylation) are detectable at 12–15% of mature values as early as 8 weeks of gestation, remain similar throughout prenatal development, do not change at birth, increase linearly over the first 5 postnatal months, and reach adult levels by 10 years of age. This ontogenic pattern differs from CYP2C9, suggesting different developmental regulatory mechanisms. Western blotting and probe substrate activity assays (mephenytoin 4'-hydroxylation) in 237 liver microsomal samples spanning 8 weeks gestation to 18 years The Journal of pharmacology and experimental therapeutics Medium 14634042
2013 The CYP2C19*17 allele is associated with increased hepatic CYP2C19 mRNA expression (~1.8-fold in heterozygotes, ~2.9-fold in homozygotes) and increased allelic mRNA expression ratio (~1.8-fold), confirming *17 as a cis-regulatory polymorphism enhancing CYP2C19 transcription. Additional regulatory variants beyond *17 also contribute to CYP2C19 expression variability in African American samples. qRT-PCR for mRNA quantification, allelic mRNA expression ratio (SNaPshot), enzyme activity assay (S-mephenytoin as substrate), sequencing of promoter region in human liver samples Drug metabolism and drug interactions Medium 23412869
2018 Dicloxacillin induces CYP2C19 (as well as CYP2C9 and CYP3A4) in vivo (significant reduction in omeprazole AUC; geometric mean ratio 0.33) and in vitro in primary human hepatocytes (dose-dependent increase in CYP expression and activity). This induction is mechanistically mediated through activation of the pregnane X receptor (PXR), as demonstrated by luciferase reporter assays. Randomized crossover pharmacokinetic clinical trial, primary human hepatocyte gene expression and activity assays, PXR luciferase reporter assay British journal of clinical pharmacology High 29105855
2020 Deep mutational scanning of CYP2C19 in cultured human cells (landing-pad system) measuring steady-state protein abundance for 7,660 single amino acid variants identified 36 of 121 missense variants that reduce CYP2C19 protein to <25% of wild-type. Variants at substrate recognition site 4 (SRS4) specifically reduced abundance in CYP2C19 but not CYP2C9, and joint analysis revealed double/triple mutant interactions in this region. These positions contribute to differing thermodynamic properties and substrate specificity between the two homologs. Deep mutational scanning (variant abundance by massively parallel sequencing, VAMP-seq) in cultured human cells Genetics High 39319420
2020 CYP2C19 missense variant scanning (DMS landing-pad system) identified 36 of 121 CYP2C19 ORF missense variants with <25% of wild-type protein expression, demonstrating that a significant fraction of genomic missense variants cause loss of CYP2C19 protein. Deep mutational scanning in human cells, protein expression quantification Clinical and translational science Medium 32004414
2016 CYP2C19 is expressed in adult human liver and in the fetal brain during neurodevelopment. Transgenic mice carrying the human CYP2C19 gene (2C19TG) showed impaired hippocampal BDNF homeostasis under stress, increased serotonin turnover reduction in hippocampus, and increased ERK1/2 and GSK3β phosphorylation, suggesting CYP2C19 modulates brain serotonin and BDNF signaling beyond classical drug metabolism. Transgenic mouse model (2C19TG), forced swim test, hippocampal BDNF and serotonin metabolite measurements, Western blot for ERK1/2 and GSK3β phosphorylation Molecular psychiatry Medium 27895323
2013 Efavirenz increases CYP2C19-mediated omeprazole metabolism (5-hydroxylation) in a CYP2C19 genotype-dependent manner: the magnitude of induction differed between CYP2C19 genotypes, and metabolic ratios of 5-hydroxylation were reduced in extensive and intermediate CYP2C19 metabolizers after efavirenz treatment, in a non-stereoselective manner. No significant association was found between CYP2B6 genotypes and this induction. Controlled pharmacokinetic clinical study in healthy subjects (n=57), CYP2C19/CYP2B6 genotyping, LC-MS/MS measurement of omeprazole enantiomers and metabolites The pharmacogenomics journal Medium 23629159
2024 CYP2C19 and CYP3A4 variants differentially affect tofacitinib metabolism: 11 CYP2C19 variants showed increased M9 (main metabolite) production and 10 showed decreased production vs. CYP2C19.1, using recombinant human enzyme systems. Myricetin inhibits tofacitinib metabolism in a non-competitive manner in rat and human liver microsomes, but competitively in CYP3A4.18 and by a mixed mechanism in CYP3A4.1 and CYP3A4.28. Recombinant human CYP2C19 and CYP3A4 variant expression system, UPLC-MS/MS metabolite quantification, enzyme kinetics in RLM and HLM Biomedicine & pharmacotherapy Medium 38719708
2004 CYP2C19 mediates stereoselective 4'-hydroxylation of R-mephobarbital: the mean plasma AUC of R-MPB was 92-fold greater in CYP2C19 poor metabolizers than in homozygous extensive metabolizers, and cumulative urinary 4'-hydroxy-MPB was 21-fold less in PMs. S-mephobarbital conversion to phenobarbital was not significantly affected by CYP2C19 genotype. A minor fraction of phenobarbital formation from MPB was associated with CYP2B6*6 allele. Controlled pharmacokinetic study in CYP2C19-genotyped subjects; plasma and urine drug/metabolite measurement; CYP2B6 genotyping Pharmacogenetics Medium 15284537
2017 CYP2C19 poor metabolizers (with two loss-of-function alleles *2/*3) have significantly lower serum dihydroxyeicosatrienoic acid (DHET, a surrogate for epoxyeicosatrienoic acids/EETs) levels compared to non-PMs in patients with microvascular angina, suggesting CYP2C19 has epoxygenase activity toward arachidonic acid producing EETs in vivo. CYP2C19 genotyping, serum DHET measurement (EET metabolite proxy) in microvascular angina patients and controls International journal of cardiology. Heart & vasculature Low 28616567

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Developmental expression of human hepatic CYP2C9 and CYP2C19. The Journal of pharmacology and experimental therapeutics 236 14634042
2005 Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies. Drug metabolism and pharmacokinetics 210 15988117
2018 Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert opinion on drug metabolism & toxicology 170 29620484
2004 Allele and genotype frequencies of CYP2C9, CYP2C19 and CYP2D6 in an Italian population. Pharmacological research 165 15177309
2003 Identification of constitutive androstane receptor and glucocorticoid receptor binding sites in the CYP2C19 promoter. Molecular pharmacology 139 12869636
2004 CYP2C19 polymorphism and proton pump inhibitors. Basic & clinical pharmacology & toxicology 138 15245569
2000 The CYP2C19 enzyme polymorphism. Pharmacology 118 10971203
2020 PharmVar GeneFocus: CYP2C19. Clinical pharmacology and therapeutics 111 32602114
1996 CYP2C19 genotype and phenotype determined by omeprazole in a Korean population. Pharmacogenetics 106 9014204
2014 CYP2C19 polymorphism influences Helicobacter pylori eradication. World journal of gastroenterology 95 25473155
2019 Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe. European journal of human genetics : EJHG 91 31358955
2018 Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine. Journal of personalized medicine 73 29385765
2011 CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population. BMC medical genetics 73 21247447
2013 The CYP2C19*17 variant is not independently associated with clopidogrel response. Journal of thrombosis and haemostasis : JTH 71 23809542
2005 Genetic variations and haplotypes of CYP2C19 in a Japanese population. Drug metabolism and pharmacokinetics 66 16141610
2008 Extraadrenal 21-hydroxylation by CYP2C19 and CYP3A4: effect on 21-hydroxylase deficiency. The Journal of clinical endocrinology and metabolism 60 18957504
2003 Allele and genotype frequency of CYP2C19 in a Tamilian population. British journal of clinical pharmacology 57 12919183
2010 Regulation of CYP2C19 expression by estrogen receptor α: implications for estrogen-dependent inhibition of drug metabolism. Molecular pharmacology 55 20675569
2014 Reactive metabolite activation by CYP2C19-mediated rhein hepatotoxicity. Xenobiotica; the fate of foreign compounds in biological systems 52 25815638
2010 Association between CYP2C19*17 and metabolism of amitriptyline, citalopram and clomipramine in Dutch hospitalized patients. The pharmacogenomics journal 52 20531370
2019 Impact of CYP1A2, CYP2C19, and CYP2D6 genotype- and phenoconversion-predicted enzyme activity on clozapine exposure and symptom severity. The pharmacogenomics journal 51 31616047
2015 MicroRNA hsa-miR-29a-3p modulates CYP2C19 in human liver cells. Biochemical pharmacology 50 26296572
1999 Phenotypes and genotypes for CYP2D6 and CYP2C19 in a black Tanzanian population. British journal of clinical pharmacology 50 10510152
2010 Association between CYP2C19 polymorphism and depressive symptoms. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 44 20468063
2019 CYP2C19-Guided Escitalopram and Sertraline Dosing in Pediatric Patients: A Pharmacokinetic Modeling Study. Journal of child and adolescent psychopharmacology 43 30817183
2019 The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes. British journal of clinical pharmacology 42 31218720
2016 The Metabolism of Clopidogrel: CYP2C19 Is a Minor Pathway. Journal of clinical pharmacology 37 27196064
2016 Elevated CYP2C19 expression is associated with depressive symptoms and hippocampal homeostasis impairment. Molecular psychiatry 36 27895323
2007 Comparisons of CYP2C19 genetic polymorphisms between Korean and Vietnamese populations. Therapeutic drug monitoring 36 17667801
2018 Association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance in clopidogrel-treated Chinese patients. Anatolian journal of cardiology 35 29350207
2006 CYP2C19 genetic polymorphism in Thai, Burmese and Karen populations. Drug metabolism and pharmacokinetics 35 16946555
2018 Genetic testing for CYP2D6 and CYP2C19 suggests improved outcome for antidepressant and antipsychotic medication. Psychiatry research 34 29699889
2019 Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 33 31649299
2020 CYP2C9 and CYP2C19: Deep Mutational Scanning and Functional Characterization of Genomic Missense Variants. Clinical and translational science 32 32004414
2014 CYP2C19 polymorphisms account for inter-individual variability of drug metabolism in cynomolgus macaques. Biochemical pharmacology 32 25036290
2011 High-density fine-mapping of a chromosome 10q26 linkage peak suggests association between endometriosis and variants close to CYP2C19. Fertility and sterility 31 21497341
2016 Genetic Polymorphisms and in Vitro Functional Characterization of CYP2C8, CYP2C9, and CYP2C19 Allelic Variants. Biological & pharmaceutical bulletin 28 27803446
2012 Effect of CYP2B6*6 and CYP2C19*2 genotype on chlorpyrifos metabolism. Toxicology 28 22281205
2018 Dicloxacillin induces CYP2C19, CYP2C9 and CYP3A4 in vivo and in vitro. British journal of clinical pharmacology 27 29105855
2018 CYP2C19 polymorphism in relation to the pharmacotherapy optimization of commonly used drugs. Die Pharmazie 26 30396378
2006 CYP2C19 polymorphism and risk for essential tremor. European neurology 26 16960452
2024 From genes to drugs: CYP2C19 and pharmacogenetics in clinical practice. Frontiers in pharmacology 25 38420192
2013 Regulatory polymorphisms in CYP2C19 affecting hepatic expression. Drug metabolism and drug interactions 25 23412869
2007 Genetic polymorphism of CYP2C19 in Maharashtrian population. European journal of epidemiology 25 17978853
2004 Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups. American journal of pharmacogenomics : genomics-related research in drug development and clinical practice 24 15651900
2023 The Effects of CYP2C19 Genotype on Proxies of SSRI Antidepressant Response in the UK Biobank. Pharmaceuticals (Basel, Switzerland) 22 37765085
2020 CYP2C19 genotype-guided antiplatelet therapy: promises and pitfalls. Pharmacogenomics 22 32723143
2009 CYP17 and CYP2C19 gene polymorphisms in patients with endometriosis. Reproductive biomedicine online 22 20113968
2022 Association between CYP2C19 and CYP2B6 phenotypes and the pharmacokinetics and safety of diazepam. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 36162369
2017 A Study on CYP2C19 and CYP2D6 Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans. Clinical and translational science 21 28296334
2023 The impact of CYP2C19 genotype on phenoconversion by concomitant medication. Frontiers in pharmacology 19 37361233
2020 The CYP2C19*2 and CYP2C19*17 Polymorphisms Influence Responses to Clozapine for the Treatment of Schizophrenia. Neuropsychiatric disease and treatment 19 32103962
2017 The CYP2C19*2 and CYP2C19*17 Polymorphisms play a Vital Role in Clopidogrel Responsiveness after Percutaneous Coronary Intervention: A Pharmacogenomics Study. Basic & clinical pharmacology & toxicology 19 28135763
2015 Association between CYP2C19 Polymorphisms and Outcomes in Cerebral Endovascular Therapy. AJNR. American journal of neuroradiology 19 26338921
2015 Genetic polymorphisms and phenotypic analysis of drug-metabolizing enzyme CYP2C19 in a Li Chinese population. International journal of clinical and experimental pathology 19 26722519
2022 Effects of CYP2C19 genetic polymorphisms on the pharmacokinetics of lacosamide in Korean patients with epilepsy. Epilepsia 17 36039802
2013 Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype dependent. The pharmacogenomics journal 17 23629159
2004 Active-site characteristics of CYP2C19 and CYP2C9 probed with hydantoin and barbiturate inhibitors. Archives of biochemistry and biophysics 17 15288804
2019 CYP2C19 genetic polymorphism in the Vietnamese population. Annals of human biology 16 31766957
2006 Determination of CYP2D6, CYP2C9 and CYP2C19 genotypes with Tag-It mutation detection assays. Expert review of molecular diagnostics 16 17140368
2023 The pharmacogenetics of CYP2D6 and CYP2C19 in a case series of antidepressant responses. Frontiers in pharmacology 15 36895946
2022 Effects of CYP2C19, CYP2C9 and CYP3A4 gene polymorphisms on plasma voriconazole levels in Chinese pediatric patients. Pharmacogenetics and genomics 15 35081606
2014 Characterization of CYP1A2, CYP2C19, CYP3A4 and CYP3A5 polymorphisms in South Brazilians. Molecular biology reports 15 24443221
2014 Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population. Molecular biology reports 15 25106522
2000 Probing CYP2C19 and CYP3A4 activities in Chinese liver microsomes by quantification of 5-hydroxyomeprazole and omeprazole sulphone. Acta pharmacologica Sinica 15 11501187
2021 Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia. Scientific reports 14 34848811
2017 CYP2C19 variants and epoxyeicosatrienoic acids in patients with microvascular angina. International journal of cardiology. Heart & vasculature 14 28616567
2016 Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina. American journal of physiology. Heart and circulatory physiology 14 27663770
2014 Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis. Fertility and sterility 14 24796765
2012 Transcriptional regulation of CYP2C19 and its role in altered enzyme activity. Current drug metabolism 14 22804232
2007 Functional characterization of two novel CYP2C19 variants (CYP2C19*18 and CYP2C19*19) found in a Japanese population. Xenobiotica; the fate of foreign compounds in biological systems 14 17455109
2024 CYP3A4 and CYP2C19 genetic polymorphisms and myricetin interaction on tofacitinib metabolism. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 13 38719708
2024 Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff. Genetics 13 39319420
2020 Distribution of CYP2C19, ABCB1 and PON1 polymorphisms in Chinese Han, Hui, Uygur and Kazak patients with coronary atherosclerotic heart disease. International journal of immunogenetics 13 32862511
2020 Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice. European journal of clinical pharmacology 13 33242107
2016 Pharmacodynamic and cytogenetic evaluation in CYP2C19*2 and CYP2C19*3 allelomorphism in South Indian population with clopidogrel therapy. International journal of cardiology 13 27915083
2008 The metabolism of CYP2C9 and CYP2C19 for gliclazide by homology modeling and docking study. European journal of medicinal chemistry 13 18541345
2004 Pharmacogenetic roles of CYP2C19 and CYP2B6 in the metabolism of R- and S-mephobarbital in humans. Pharmacogenetics 13 15284537
2021 Pharmacogenomics in the United States Community Pharmacy Setting: The Clopidogrel-CYP2C19 Example. Pharmacogenomics and personalized medicine 12 34040417
2021 Genetic polymorphism of CYP2C19 and subcortical variability in the human adult brain. Translational psychiatry 12 34497262
2007 Relative roles of CYP2C19 and CYP3A4/5 in midazolam 1'-hydroxylation. Xenobiotica; the fate of foreign compounds in biological systems 12 17614006
2019 Development and validation of T-ARMS-PCR to detect CYP2C19*17 allele. Journal of clinical laboratory analysis 11 31441095
2015 CYP2C19 drug-drug and drug-gene interactions in ED patients. The American journal of emergency medicine 11 26639454
2013 Investigation of CYP2C19 allele and genotype frequencies in Iranian population using experimental and computational approaches. Thrombosis research 11 24315317
2001 CYP2C19 genotype determines enzyme activity and inducibility of S-mephenytoin hydroxylase. Clinica chimica acta; international journal of clinical chemistry 11 11694260
2024 The Diversity of CYP2C19 Polymorphisms in the Thai Population: Implications for Precision Medicine. The application of clinical genetics 10 38975048
2024 Inflammation altered correlation between CYP2C19 genotype and CYP2C19 activity in patients receiving voriconazole. Clinical and translational science 10 39010708
2023 Clinical Impact of the CYP2C19 Gene on Diazepam for the Management of Alcohol Withdrawal Syndrome. Journal of personalized medicine 10 36836519
2022 Therapeutic drug monitoring and CYP2C19 genotyping guide the application of voriconazole in children. Translational pediatrics 10 36072540
2020 Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy. BMC cardiovascular disorders 10 32493215
2019 Comparison between MassARRAY and pyrosequencing for CYP2C19 and ABCB1 gene variants of clopidogrel efficiency genotyping. Molecular membrane biology 10 30916611
2019 Genetic Polymorphism of CYP2C19 in Pakistani Population. Iranian journal of pharmaceutical research : IJPR 10 31531091
2014 The influence of the CYP2C19*10 allele on clopidogrel activation and CYP2C19*2 genotyping. Pharmacogenetics and genomics 10 24945780
2023 From gene to dose: Long-read sequencing and *-allele tools to refine phenotype predictions of CYP2C19. Frontiers in pharmacology 9 36937863
2023 PBPK modeling to predict the pharmacokinetics of pantoprazole in different CYP2C19 genotypes. Archives of pharmacal research 9 38150171
2016 Stereoselective hydroxylation by CYP2C19 and oxidation by ADH4 in the in vitro metabolism of tivantinib. Xenobiotica; the fate of foreign compounds in biological systems 9 26899628
2016 Association of MDR1, CYP2D6, and CYP2C19 gene polymorphisms with prophylactic migraine treatment response. Journal of the neurological sciences 9 27288795
2015 Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand acute coronary syndrome population. Internal medicine journal 9 25583161
2014 CYP2C19 polymorphism increases the risk of endometriosis. Journal of assisted reproduction and genetics 9 25403437
2018 Response to clopidogrel and of the cytochrome CYP2C19 gene polymorphism. La Tunisie medicale 8 30325490

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