CYP2C19 is highly polymorphic: 39 haplotypes have been characterised by their impact on drug metabolism. This genetic heterogeneity is associated with significant pharmacokinetic variation between individuals, which affects drug efficacy and the risk of adverse effects.

The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C19 gene. CYP2C19 genetic variation is associated with altered drug metabolism and response. As of February 2020, the CYP2C19 expert panel has designated two novel alleles (*36 and *37) and three new suballeles. Considering CYP2C19*1 through *35 (excluding the CYP2C19*36 and *37 deletion alleles), hundreds of allele combinations are possible, and thus, the number of genotypes in a population or patient cohort can be quite large.

This CPIC resource provides an updated "CYP2C19 allele frequency table" that lists the defined CYP2C19 star alleles, their functional status (normal, no function, increased function, etc.), and calculated allele frequencies across multiple biogeographical populations. The accompanying CPIC documentation explains that these allele frequency tables are used in CPIC guidelines to assign metabolizer phenotypes (poor, intermediate, normal, rapid, and ultrarapid metabolizers) based on CYP2C19 diplotypes.

The normal "wild type" allele is CYP2C19*1 and is reported when no variant is detected. The table lists selected CYP2C19 alleles and their nomenclature, supporting the point that CYP2C19 has multiple recognized star alleles with different functional effects.

CYP2C19 drug metabolism is variable among individuals. Some individuals have CYP2C19 genetic variants that lead to severely diminished or absent CYP2C19 catalytic activity (ie, poor metabolizers).

The CYP2C19 gene is located on chromosome 10q23.33 and to date, **39 alleles and 2000 SNPs have been identified** (Shao et al., 2020). Among these variants, CYP2C19*2 and CYP2C19*3 are the most frequent and have received the greatest attention, as they identify poor metabolizers. Understanding CYP2C19 as a metabolizing enzyme will enable healthcare professionals to make decisions regarding drug selection and dosing based on each individual’s genetic makeup to reach a safe and effective treatment.

The Pharmacogene Variation Consortium (PharmVar) catalogs star (*) allele nomenclature for the polymorphic human CYP2C19 gene. CYP2C19 genetic variation is associated with altered drug metabolism and response for many commonly prescribed medications, including proton pump inhibitors, antiplatelet agents, and certain antidepressants and anticonvulsants. Alleles are assigned function (e.g., normal, no, decreased, increased function) which is used in clinical pharmacogenetic implementation guidelines.

The ClinPGx CPIC gene page for CYP2C19 links to "gene-specific information tables (i.e. CYP2C19 allele definition, allele functionality, frequency and diplotype-phenotype tables)." These tables describe how specific CYP2C19 star alleles are classified by function and how combinations of alleles (diplotypes) are translated into metabolizer phenotypes that affect drug metabolism (e.g., poor, intermediate, normal, rapid, ultrarapid).

The PharmVar "Gene Info" document for CYP2C19 notes that "Allele frequencies CYP2C19 allele frequency tables have been developed for CPIC guidelines and are available through the PharmGKB" and that "A comprehensive list of frequencies and references can be found in the CYP2C19 allele frequency Table in the source tab." It also states that "For some alleles, the assigned activity may differ" and that activity of particular alleles and substrates should be extrapolated with caution, underscoring that multiple CYP2C19 alleles with different activities influence drug metabolism.

The purpose of this study is to assess the frequencies of several actionable variants in the highly polymorphic CYP2C19 gene in a large unselected sample. The well-characterized variants of CYP2C19 are the increased-function allele *17 and the no-function alleles *2 and *3, and these allelic combinations correspond to different phenotypic metabolism rates.

CYP2C19 is located on chromosome 10q23.33 and belongs to class 2 of the cytochrome P450 superfamily. To date, **39 alleles and 2000 SNPs have been identified** in CYP2C19 (Shao et al., 2020). Among these variants, CYP2C19*2 and CYP2C19*3 are the most frequent and have received the greatest attention, as they identify poor metabolizers.

Table 1 PharmVar gene and membership demographics... CYP2C19 *1-*35 33e haplotypes per gene. Footnote e: The CYP2C19 gene has 33 star alleles (*1 through *35) catalogued at the time of this analysis, excluding some deletion alleles and suballeles. PharmVar continues to add new alleles as they are identified and confirmed.

PharmVar: CYP2C19. The database lists individual star alleles (e.g., CYP2C19*1.005, CYP2C19*1.006, CYP2C19*27, etc.) with unique PharmVar IDs. The star allele list includes alleles from *1 onward and indicates multiple defined alleles and suballeles. Each star allele entry includes function annotations such as normal function, no function, decreased function, or increased function, which are relevant for drug metabolism.

CYP2C19 and CYP2D6 are important drug-metabolizing enzymes involved in the metabolism of around 30% of all medications. The paper describes CYP2C19 as highly polymorphic and examines clinically important allele frequencies across Europe.

The archived CYP2C19 allele table lists star alleles including CYP2C19*1 through CYP2C19*35 (e.g., CYP2C19*29, CYP2C19*30, CYP2C19*31, CYP2C19*32, CYP2C19*33, etc.). The table shows, for each star allele, the defining sequence variants and associated functional annotations such as normal, no function, or decreased function. These star alleles represent different haplotypes of the CYP2C19 gene relevant to variability in drug metabolism.

CYP2C19 is a highly polymorphic gene encoding a cytochrome P450 enzyme involved in the biotransformation of many commonly prescribed drugs. Multiple no-function (e.g., *2, *3), decreased-function (e.g., *9), and increased-function (e.g., *17) alleles have been described. Individuals carrying one or two no-function alleles have reduced or absent CYP2C19 activity and are classified as intermediate or poor metabolizers, whereas carriers of *17 have increased enzyme activity and are classified as rapid or ultrarapid metabolizers.

CYP2C19 is polymorphic, and multiple variant alleles can result in altered enzyme activity. The most common loss-of-function alleles are CYP2C19*2 and CYP2C19*3, which lead to absent enzyme activity. CYP2C19*17 is a gain-of-function allele associated with increased transcription and increased enzyme activity. These genetic differences translate into poor, intermediate, extensive (normal), and ultra-rapid metabolizer phenotypes for CYP2C19 substrates.

This Clinical and Translational Science paper reports allele frequencies for common CYP2C19 variants and notes that across all populations, "the common no-function allele *2 and the increased-function allele *17 were observed at rates of 15.2% and 20.4%, respectively, whereas *3 was rare overall (0.3%)." It emphasizes that these alleles encode different enzyme activities and that genotype combinations correspond to CYP2C19 metabolizer phenotypes with clinical implications for drug metabolism.

The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C19 gene. Numerous variants were subsequently reported and continue to be identified. While many CYP2C19 variants have been reported as having no function, a notable discovery in CYP2C19 pharmacogenetics was the identification of the CYP2C19*17 allele, which is associated with increased enzyme activity and more rapid drug clearance. Genetic variation, contributing to interindividual variability in CYP2C19 activity, is caused by SNVs within coding regions; gene copy number variation may also affect activity in rare cases.

CYP2C19 is highly polymorphic, and genetic variation affects enzyme activity and thus the metabolism of proton pump inhibitors (PPIs) such as omeprazole, lansoprazole, and others. Loss-of-function alleles (e.g., *2, *3) result in decreased or no function, whereas the increased-function allele *17 results in higher CYP2C19 activity. Based on their diplotype, individuals are assigned CYP2C19 metabolizer phenotypes: poor, intermediate, normal, rapid, or ultrarapid metabolizers.

Because the DNA sequence of CYP2C19 is highly polymorphic, this may account for much of the variability in the pharmacokinetics of drugs metabolized by CYP2C19. The phenotype of CYP2C19 metabolic capacity can be categorized based on genotypes and includes extensive metabolizers (two wild-type functional alleles), intermediate metabolizers (two reduced functional alleles or one null allele and a functional allele), and poor metabolizers (two non-functional alleles) of drugs. To date, the pharmacogenetic data on CYP2C19 clearly support that genetic variants alter the drug responses of its substrate drug.

The ClinPGx entry for CYP2C19*2 describes it as a "no function" allele and provides allele counts and frequencies across biogeographical groups (e.g., AFR, AMR, EAS, EUR), illustrating that this loss-of-function variant is common in many populations. The functional annotation of CYP2C19*2 as no-function is used in CPIC diplotype-to-phenotype tables to identify poor or intermediate metabolizers, which impacts the metabolism of CYP2C19 substrate medications.

CYP2C19 allele definition tables map variants to star alleles and curate the reference material used to interpret CYP2C19 genotype results. This supports the claim that many CYP2C19 alleles exist and are catalogued for pharmacogenomic use.

CYP2C19 is one of the most extensively studied polymorphic drug-metabolizing enzymes. More than 30 allelic variants of CYP2C19 have been identified, many of which result in altered enzyme activity. These alleles give rise to different metabolizer phenotypes that influence the pharmacokinetics and pharmacodynamics of various drugs, including proton pump inhibitors, antiepileptics, antidepressants, and antiplatelet agents.

PharmGKB’s CYP2C19 reference materials page hosts "gene-specific information tables" that include an allele definition table and an allele functionality table for CYP2C19, along with an allele frequency table. These curated tables list the catalog of CYP2C19 star alleles, classify each allele by predicted function (e.g., normal, no function, increased function), and map diplotypes to metabolizer phenotypes relevant for clinical pharmacogenetic dosing recommendations.

CYP2C19*2 has a minor allele frequency ranging from 13% to 54% in most major racial and ethnic groups, and consequently is the most common CYP2C19 allele in many populations. This shows substantial genetic variability within CYP2C19.

CYP2C19 is a highly polymorphic gene with numerous star alleles identified worldwide. Common loss-of-function alleles include *2 and *3, whereas *17 is a gain-of-function allele. The distribution of these alleles varies substantially across populations and contributes to interindividual and interethnic variability in CYP2C19 metabolizer status and drug response.

CYP2C19 exhibits high genetic variability, with numerous functional variants described. These include nonfunctional alleles (e.g., *2, *3, *4, *5), decreased-function alleles, and the increased-function allele *17. The presence of these alleles results in a spectrum of CYP2C19 metabolic phenotypes, from poor to ultrarapid metabolizers, affecting the metabolism and clinical efficacy of multiple medications.

In addition to the normal CYP2C19*1 allele, the CYP2C19 gene can have **up to 35 different alleles (named in order of discovery)**, many of which are associated with altered enzyme function, resulting in poor, intermediate, rapid, or ultra-rapid drug metabolism. The group’s first set of recommendations identify a minimum set of alleles for inclusion in clinical CYP2C19 genotyping panels. The alleles recommended for inclusion in tier one for clinical CYP2C19 genotyping panels are CYP2C19*2 and CYP2C19*3, which are loss-of-enzymatic-function alleles, and CYP2C19*17, which is associated with increased function of the enzyme.

CYP2C19 is a highly polymorphic gene with numerous genetic variants that can alter the enzyme’s metabolic activity. A common novel CYP2C19 gene variant causes ultra-rapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Specific star alleles such as CYP2C19*2 and CYP2C19*3 are associated with no function, whereas CYP2C19*17 is associated with increased enzyme activity.

Genetic variation in the CYP2C19 gene plays a major role in inter-individual variability in drug response. Variant CYP2C19 alleles distribute differently across ethnic groups, and the document lists multiple major human CYP2C19 alleles and their associated SNPs.

ClinPGx curates literature and variant information for pharmacogenes including CYP2C19. It describes the identification and functional characterization of new potentially defective alleles of human CYP2C19 and links these haplotypes to altered enzyme activity. The database organizes CYP2C19 variants into haplotypes that are used in pharmacogenetic testing and phenotype prediction.

CYP2C19 is a highly polymorphic cytochrome P450 enzyme used in pharmacogenetics; different star alleles can reduce, eliminate, or increase enzyme activity, changing the metabolism of drugs such as clopidogrel, proton-pump inhibitors, and some antidepressants.