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CYP2C19 gene

cytochrome P450 family 2 subfamily C member 19

Normal Function

The CYP2C19 gene is a member of the cytochrome P450 gene family. Enzymes produced from cytochrome P450 genes are involved in the formation and breakdown (metabolism) of various molecules and chemicals within cells. The CYP2C19 gene provides instructions for making an enzyme that is found primarily in liver cells in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport.

The CYP2C19 enzyme plays a role in the processing or metabolizing of at least 10 percent of commonly prescribed drugs, including a drug called clopidogrel (also known as Plavix). Clopidogrel is an antiplatelet drug, which means that it prevents blood cells called platelets from sticking together (aggregating) and forming blood clots. The CYP2C19 enzyme converts clopidogrel to its active form, which is necessary for the drug to function in the body. The active drug then stops (inhibits) a receptor protein known as P2RY12 that is found on the surface of platelets. During clot formation, the P2RY12 receptor protein helps platelets cluster together to form a clot in order to seal off damaged blood vessels and prevent blood loss.

Health Conditions Related to Genetic Changes

Clopidogrel resistance

Multiple variations (polymorphisms) in the CYP2C19 gene have been associated with clopidogrel resistance, a condition in which the drug clopidogrel is less effective than normal in people who are treated with it. The polymorphisms that are associated with clopidogrel resistance decrease the enzyme's ability to convert the drug to its active form.

The normal version of the gene, written as CYP2C19*1, provides instructions for producing a normally functioning CYP2C19 enzyme. If a person has two copies of the CYP2C19*1 version of the gene in each cell, they are able to convert clopidogrel normally. The two most common CYP2C19 gene polymorphisms associated with clopidogrel resistance (known as CYP2C19*2 and CYP2C19*3) result in the production of a nonfunctional CYP2C19 enzyme that is unable to activate clopidogrel.

Individuals with clopidogrel resistance can be classified into two groups: intermediate metabolizers or poor metabolizers. People who have one copy of the CYP2C19*1 version of the gene and one copy of either the CYP2C19*2 or CYP2C19*3 version of the gene have a reduced ability to convert clopidogrel to its active form and are classified as intermediate metabolizers. People who have the CYP2C19*2 or CYP2C19*3 versions of the gene for both copies of the gene can convert very little or none of the drug and are classified as poor metabolizers. Because conversion of clopidogrel to its active form is impaired in people with clopidogrel resistance, the drug is unable to inhibit P2RY12 receptor function. Without active clopidogrel to interfere, the P2RY12 receptor continues to promote platelet aggregation and blood clot formation, which can lead to heart attacks, strokes, and thromboses in individuals with a history of these conditions.

It is important to note that not all individuals with CYP2C19 gene mutations have clopidogrel resistance. These individuals who are at increased risk for developing clopidogrel resistance may or may not have a bad reaction when treated with the drug. In addition to changes in specific genes, many other factors, including sex, age, weight, diet, and other medications, play a role in how the body reacts to clopidogrel.

More About This Health Condition

Other disorders

Polymorphisms in the CYP2C19 gene that are associated with clopidogrel resistance (described above) can also affect the processing of other drugs. Because the CYP2C19 enzyme is involved in the metabolism of many drugs, changes to the enzyme can have wide-ranging effects. Other drugs that are affected by CYP2C19 gene polymorphisms include proton pump inhibitors, used to treat stomach ulcers and other conditions; antidepressants, used to treat psychiatric disorders; anticonvulsants, used to treat seizure disorders; hypnotics and sedatives, used as sleep aids; antimalarial drugs, used to prevent malarial infections; and antiretroviral drugs, used to prevent viruses from replicating.

Most often, changes in the CYP2C19 gene lead to impaired metabolism of these drugs, which reduces their effectiveness. One change in the CYP2C19 gene (known as CYP2C19*17) increases the enzyme's ability to metabolize drugs. Individuals with two copies of the CYP2C19*17 polymorphism are typically classified as ultra-rapid metabolizers.

Other Names for This Gene

  • (R)-limonene 6-monooxygenase
  • (S)-limonene 6-monooxygenase
  • (S)-limonene 7-monooxygenase
  • CPCJ
  • CYP2C
  • CYPIIC17
  • CYPIIC19
  • cytochrome P-450 II C
  • cytochrome P450 2C19 precursor
  • cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 19
  • cytochrome P450-11A
  • cytochrome P450-254C
  • flavoprotein-linked monooxygenase
  • mephenytoin 4'-hydroxylase
  • mephenytoin 4-hydroxylase
  • microsomal monooxygenase
  • P450C2C
  • P450IIC19
  • S-mephenytoin 4-hydroxylase
  • xenobiotic monooxygenase

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases


  • Hirota T, Eguchi S, Ieiri I. Impact of genetic polymorphisms in CYP2C9 and CYP2C19 on the pharmacokinetics of clinically used drugs. Drug Metab Pharmacokinet. 2013;28(1):28-37. doi: 10.2133/dmpk.dmpk-12-rv-085. Epub 2012 Nov 20. Citation on PubMed
  • Scott SA, Sangkuhl K, Shuldiner AR, Hulot JS, Thorn CF, Altman RB, Klein TE. PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenet Genomics. 2012 Feb;22(2):159-65. doi: 10.1097/FPC.0b013e32834d4962. Citation on PubMed or Free article on PubMed Central
  • Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, Klein TE, Sabatine MS, Johnson JA, Shuldiner AR; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013 Sep;94(3):317-23. doi: 10.1038/clpt.2013.105. Epub 2013 May 22. Citation on PubMed or Free article on PubMed Central
  • Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; Writing Committee Members; Holmes DR Jr, Dehmer GJ, Kaul S, Leifer D, O'Gara PT, Stein CM. ACCF/AHA Clopidogrel clinical alert: approaches to the FDA "boxed warning": a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. Circulation. 2010 Aug 3;122(5):537-57. doi: 10.1161/CIR.0b013e3181ee08ed. Epub 2010 Jun 28. No abstract available. Citation on PubMed
  • Uppugunduri CR, Daali Y, Desmeules J, Dayer P, Krajinovic M, Ansari M. Transcriptional regulation of CYP2C19 and its role in altered enzyme activity. Curr Drug Metab. 2012 Oct;13(8):1196-204. doi: 10.2174/138920012802850146. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.