Gene:
CYP2J2
cytochrome P450, family 2, subfamily J, polypeptide 2

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The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP No Clinical Annotations available No Variant Annotations available
rs890293 -76G>T, 30364412C>A, 4930G>T, 60392494C>A, CYP2J2*7, CYP2J2:G-50T, CYP2J2:G-76T
C > A
5' Flanking
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  None
PharmGKB Accession Id: PA27112

Details

Cytogenetic Location: chr1 : p31.3 - p31.2
GP mRNA Boundary: chr1 : 60358980 - 60392423
GP Gene Boundary: chr1 : 60355980 - 60402423
Strand: minus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

CYP2J2 is a member of the cytochrome P450 (CYP) family of monooxygenases, and, in humans, is the sole member of the CYP2J subfamily [Article:9570962]. Specifically, CYP2J2 is an epoxygenase that catalyzes epoxide formation at the site of a carbon-carbon double bond in the substrate, as do other CYP epoxygenases, such as CYP2C8 and CYP2C9 [Article:15466638].

The therapeutic agents ebastine [Article:16842392], astemizole, terfenadine, diclofenac, and bufurarol are metabolized by CYP2J2 [Article:15861034]. A recent study screening 139 marketed therapeutic agents and compounds identified albendazole, amiodarone, cyclosporine A, danazol, mesoridazine, nabumetone, tamoxifen, and thioridazine as CYP2J2 substrates [Article:19923256]. These findings demonstrate the ability of CYP2J2 to metabolize structurally diverse compounds. The substrates identified for CYP2J2 were also metabolized by CYP3A4, but with differences in regioselectivity [Article:19923256]. For large compounds, CYP2J2 metabolism was more restricted to a single site, as compared with CYP3A4, which metabolized substrates at multiple sites [Article:19923256]. A study in microsomes from human livers and human small intestines investigated the metabolism of astemizole by CYP2J2 [Article:12386130]. This study found that the CYP2J2 substrates arachidonic acid (AA) and ebastine strongly inhibited astemizole O-demethylation in microsomes from human small intestines and in in vitro experiments with recombinant CYP2J2 [Article:12386130]. A follow-up study found an inhibition of alpha-naphthoflavone, ketoconazole, troglitazone, tranylcypromine, ebastine and terfenadine on the rate of astemizole O-demethylation in human small intestinal microsomes and on the rate of astemizole O-demethylation in recombinant CYP2J2 microsomes [Article:12851038].

AA and linoleic acid (LA) are endogenous substrates of CYP2J2 [Article:15466638], [Article:11901223]. CYP epoxygenases catalyze the metabolism of AA to four regioisomeric epoxyeicosatrienoic acids (EETs): 14,15-EET; 11,12-EET; 5,6-EET and 8,9-EET [Article:10681399]. EETs have been shown to possess many biologically relevant properties, such as inducing membrane hyperpolarization and vasodilation, reducing inflammation via inhibition of transcription factor NF-kB, and increasing fibrinolytic activity (reviewed in [Article:11451964]). CYP2J2-derived EETs have been shown to be cardioprotective following ischemia [Article:18973759] and after doxorubicin treatment [Article:19429816] in animal studies using a transgenic mouse model over-expressing the human CYP2J2 isoform. How these findings translate into humans needs to be further investigated.

CYP2J2 activates the nuclear peroxisome proliferator-activated receptor alpha (PPARalpha), a controller of lipid metabolism and inflammation, in vitro and in vivo [Article:19823578]. A CYP2J2 cDNA was cloned in 1996 by Wu et al. [Article:8631948], and the CYP2J2 genomic region was cloned in 2002 by King et al. [Article:11901223]. CYP2J2 was mapped to human chromosome 1 [Article:9570962] and the genomic region spans approximately 40 kb [Article:11901223], encoding a 1.9 kb transcript from which a 502 amino acid protein with a molecular mass of 57.7 kilodaltons is produced [Article:8631948]. The CYP2J2 gene, like other CYP2 family genes, is comprised of 9 exons and 8 introns [Article:11901223]. Four binding site consensus sequences for the SP1 transcription factor are found in the wild-type CYP2J2 promoter [Article:15466638]. As expected for members of the CYP family, there is a heme-binding motif in the CYP2J2 predicted protein sequence [Article:8631948].

The presence of CYP2J2 protein in microsomes [Article:8631948] is indicative of its subcellular localization to the endoplasmic reticulum (ER). CYP2J2 is expressed at high levels in the heart, particularly in cardiac myocytes and endothelial cells in coronary arteries [Article:8631948], [Article:10455056]. Other tissues, including the liver, kidney, lung, pancreas, and gastrointestinal tract, also express CYP2J2 [Article:11901223]. CYP2J2 showed selective distribution in different brain regions [Article:12772594], [Article:19359404]. All of these tissues also exhibit fetal expression of CYP2J2 [Article:16868033].

Due to its predicted role in cardiovascular health, CYP2J2 has been extensively studied. The role of CYP2J2 in cancer is also being investigated. In vitro experiments showed a high and selective expression of CYP2J2 in different human tumor tissues and cell lines [Article:19550113]. Inhibitors of CYP2J2 related to the drug terfenadine showed effectiveness as antitumor agents in in vitro assays and in murine xenograft models [Article:19289568]. Increased CYP2J2 expression has been observed in tumor samples from patients with advanced epithelial ovarian cancer [Article:17908963], and in vitro studies showed that overexpression of CYP2J2 promoted human cancer metastasis [Article:17638876].

Note: The CYP2J2 gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.

Citation PharmGKB summary: cytochrome P450, family 2, subfamily J, polypeptide 2: CYP2J2. Pharmacogenetics and genomics. 2010. Berlin Dorit S, Sangkuhl Katrin, Klein Teri E, Altman Russ B. PubMed
History

Submitted by Dorit Berlin

Updated by Dorit Berlin, Katrin Sangkuhl

Variant Summaries rs890293
Drugs
Chemical (2)
arachidonic acid, linoleic acid
Diseases

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

PharmGKB contains no curated pathways for this gene. If you would like to volunteer to work on a pathway, please let us know.

External Pathways

Links to non-PharmGKB pathways.

  1. eicosanoid metabolism - (BioCarta via Pathway Interaction Database)
  2. Fatty acids - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Curated Information ?

Publications related to CYP2J2: 17

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of drugs withdrawn from the market. Pharmacogenomics. 2012. Zhang Wei, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: cytochrome P450, family 2, subfamily J, polypeptide 2: CYP2J2. Pharmacogenetics and genomics. 2010. Berlin Dorit S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Changes in the gene expression profile of gastric cancer cells in response to ibuprofen: a gene pathway analysis. The pharmacogenomics journal. 2010. Bonelli P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part II. Clinical pharmacokinetics. 2010. Staatz Christine E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effect of cytochrome P450 polymorphism on arachidonic acid metabolism and their impact on cardiovascular diseases. Pharmacology & therapeutics. 2010. Zordoky Beshay N M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identification of novel substrates for human cytochrome P450 2J2. Drug metabolism and disposition: the biological fate of chemicals. 2010. Lee Caroline A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The common functional polymorphism -50G>T of the CYP2J2 gene is not associated with ischemic coronary and cerebrovascular events in an urban-based sample of Swedes. Journal of hypertension. 2010. Fava Cristiano, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The epoxygenases CYP2J2 activates the nuclear receptor PPARalpha in vitro and in vivo. PloS one. 2009. Wray Jessica A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Role of cytochrome P450 2C8 and 2J2 genotypes in calcineurin inhibitor-induced chronic kidney disease. Pharmacogenetics and genomics. 2008. Smith Helen E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cytochrome P450 2J2*7 polymorphisms in Japanese, Mongolians and Ovambos. Cell biochemistry and function. 2008. Takeshita Haruo, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Common variation in cytochrome P450 epoxygenase genes and the risk of incident nonfatal myocardial infarction and ischemic stroke. Pharmacogenetics and genomics. 2008. Marciante Kristin D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The CYP2J2 G-50T polymorphism and myocardial infarction in patients with cardiovascular risk profile. BMC cardiovascular disorders. 2008. Börgel Jan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identification and functional characterization of novel CYP2J2 variants: G312R variant causes loss of enzyme catalytic activity. Pharmacogenetics and genomics. 2005. Lee Sang Seop, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2. Circulation. 2004. Spiecker Martin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annual review of pharmacology and toxicology. 2003. Ding Xinxin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cloning of CYP2J2 gene and identification of functional polymorphisms. Molecular pharmacology. 2002. King Lorraine M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart. The Journal of biological chemistry. 1996. Wu S, et al. PubMed

LinkOuts

Entrez Gene:
1573
OMIM:
601258
UCSC Genome Browser:
NM_000775
RefSeq RNA:
NM_000775
RefSeq Protein:
NP_000766
RefSeq DNA:
AC_000044
AC_000133
NC_000001
NG_007931
NT_032977
NW_001838579
NW_921351
ALFRED:
LO007920S
LO031629V
HuGE:
CYP2J2
Comparative Toxicogenomics Database:
1573
ModBase:
P51589
HumanCyc Gene:
HS05902
HGNC:
2634

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