The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for tacrolimus based on CYP3A5 genotype (PMID:21412232). They found evidence to support an interaction between tacrolimus and CYP3A5. However, they make no dosing recommendations at this time, due to fact that "in Dutch transplantation hospitals the tacrolimus dose is titrated in response to therapeutic drug monitoring."
| Genotype | Therapeutic Dose Recommendation | Level of Evidence | Clinical Relevance |
|---|---|---|---|
| CYP3A5 *1/*1 | None | Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. | Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test. |
| CYP3A5 *1/*3 | None | Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. | Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x109/l; leucopenia 1.0-2.0x109/l; thrombocytopenia 25-50x109/l; severe diarrhea. |
- *See Methods or PMID: 18253145 for definition of "good quality."
- S: statistically significant difference.
PharmGKB contains no drug labels with pharmacogenomic information for this gene. To report a drug label with PGx, click here.
Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below. Please follow the link in the "Position" column for more information about a particular variant. Each link in the "Position" 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.
To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.
| Position ? | Drug ? | Relevance ? |
Strength of Evidence ? |
||
|---|---|---|---|---|---|
| rs776746 | cyclosporine dose easy to predict | 1 | |||
Download a summary of all Clinical Annotations available.
Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.
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.
PharmGKB contains no genetic tests for this gene. To report genetic tests, click here.
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.
Links in the "Drugs" column lead to PharmGKB Drug Pages.
|
Variant?
(build 132) |
Alternate Names ? | Drugs ? |
Alleles
?
(+ chr strand) |
Function ? |
Amino Acid?
Translation |
|
|---|---|---|---|---|---|---|
| rs10264272 | CYP3A5*6, CYP3A5:711G>A, CYP3A5:Lys208Lys, c.1226G>A, c.1245G>A, c.624G>A, c.867G>A, c.975G>A, c.986G>A, g.19787G>A, g.201839G>A, g.254871G>A, g.37295678C>T | G > A | Not Available | Lys208Lys | ||
| rs15524 | G/A | Not Available | ||||
| rs41303343 | AT > A | Not Available | Pro345Pro | |||
| rs4646457 | C/A | Not Available | ||||
| rs4646458 | T/G | Not Available | ||||
| rs76293380 | c.1035delT, c.1397delT, c.1637delT, c.2741delT, g.214280delT, g.267312delT, g.32228delT, g.37283237delA, p.Pro345fx | T | Not Available | Pro | ||
| rs776746 | CYP3A5*1, CYP3A5*3, CYP3A5*3C, CYP3A5:6986A>G, c.219-237G>A, c.321-1G>A, c.581-237G>A, c.689-1G>A, g.12083G>A, g.194135G>A, g.247167G>A, g.37303382C>T, g.6986A>G, intron 3 splicing defect, rs776746 A>G | T/C | Not Available |
Overview
| Alternate Names: | CYPIIIA5; aryl hydrocarbon hydroxylase; cytochrome P-450; cytochrome P450 3A5; cytochrome P450 HLp2; cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 5; cytochrome P450-PCN3; flavoprotein-linked monooxygenase; microsomal monooxygenase; niphedipine oxidase; xenobiotic monooxygenase |
|---|---|
| Alternate Symbols: | CP35; DKFZp686L16231; FLJ31317; P450PCN3; PCN3 |
| PharmGKB Accession Id: | PA131 |
Details
| Cytogenetic Location: | chr7 : q22.1 - q22.1 |
|---|---|
| GP mRNA Boundary†: | chr7 : 99245817 - 99277621 |
| GP Gene Boundary†: | chr7 : 99242817 - 99287621 |
| Strand: | minus |
| Product Name: | No data available |
PharmGKB Curated Pathways
Pathways created internally by PharmGKB based primarily on literature evidence.
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Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics
Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
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Carbamazepine Pathway, Pharmacokinetics
Stylized liver cell depicting candidate genes involved in the pharmacokinetics of carbamazepine.
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Clopidogrel Pathway, Pharmacokinetics
Clopidogrel metabolism.
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Cyclophosphamide Pathway, Pharmacokinetics
Model human liver cell showing genes involved in the metabolism of cyclophosphamide.
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Erlotinib Pathway, Pharmacokinetics
Model human liver cell showing genes involved in the transportation and metabolism of Erlotinib.
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Etoposide Pathway, Pharmacokinetics/Pharmacodynamics
Etoposide cellular disposition and effects.
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Fluoxetine Pathway, Pharmacokinetics
Representation of the candidate genes involved in the metabolism of fluoxetine.
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Fluvastatin Pathway, Pharmacokinetics
Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
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Gefitinib Pathway, Pharmacokinetics
Representation of the candidate genes involved in the transportation and metabolism of gefitinib.
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Ifosfamide Pathway, Pharmacokinetics
Model human liver cell showing genes involved in the metabolism of ifosfamide.
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Irinotecan Pathway, Pharmacokinetics
Model human liver cell showing blood, bile and intestinal compartments, indicating tissue specific involvement of genes in the irinotecan pathway.
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Phenytoin Pathway, Pharmacokinetics
Genes involved in the metabolism of phenytoin in the human liver cell.
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Statin Pathway - Generalized, Pharmacokinetics
Representation of the superset of all genes involved in the transport, metabolism and clearance of statin class drugs.
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Tamoxifen Pathway, Pharmacokinetics
Tamoxifen metabolism in the liver.
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Taxane Pathway, Pharmacokinetics
Representation of the genes involved in the metabolism and transport of paclitaxel and docetaxel, and the downstream effects of the drugs.
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Vinka Alkaloid Pathway, Pharmacokinetics
Representation of the genes involved in the metabolism, transport, and downstream effects of the vinca alkaloid vincristine.
External Pathways
Links to non-PharmGKB pathways.
Datasets
- Bone mineral density in tamoxifen patients
- Hepatic CYP3A5 predicts Saquinavir clearance
- Hot flashes in tamoxifen patients
- In vivo and in vitro characterization of variants
- Irinotecan and CYP3A5 Genotype
- Irinotecan Clinical Data
- Lipid measurements in tamoxifen study
- Lipid measurements in tamoxifen study - set 2
- Meperidine N-demethylation by human CYP450 isoforms
- Metabolism of yohimbine by human CYP450 isoforms
- Microsomal study of midazolam, mRNA/protein levels
- Midazolam and docetaxel clearance
- Patient responses to tamoxifen
- Pharmacogenetic Risk Factors for Osteonecrosis of the Hip Among Children With Leukemia
- Pharmacokinetics of etoposide, catechol metabolite
- Pharmacokinetics of irinotecan in cancer patients
- Pharmacokinetics of Tamoxifen at 4 months
- Protein expression of genes in the irinotecan pathway
- Risk of therapy-related acute myeloid leukemia
- RNA expression in metabolite and transport genes
- Tacrolimus dosing and outcome in lung transplant patients
- Tacrolimus dosing and Steroid Weaning in pediatric heart transplant patients
- Tamoxifen Clinical Trial Phenotypic Dataset
- Thyroid binding globulin in tamoxifen patients
- Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of CYP3A5
- A Comparison of the Pharmacokinetics and Pharmacodynamics of Docetaxel between African-American and Caucasian Cancer Patients: CALGB 9871
- P450s involved in Efavirenz Metabolism
- PHARMACOKINETICS OF ERLOTINIB and ERLOTINIB induced TOXICITY
- Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African Americans.
- Prevalence of common disease-associated variants in Asian Indians
- The Influence of CYP3A5 Expression on the Extent of Hepatic CYP3A Inhibition Is Substrate-Dependent: An in Vitro-in Vivo Evaluation
LinkOuts
- Web Resource:
- http://www.imm.ki.se/CYPalleles/cyp3a5.htm
- UniProtKB:
- CP3A5_HUMAN (P20815)
- Ensembl:
- ENSG00000106258
- GenAtlas:
- CYP3A5
- GeneCard:
- GC07M099246 (1577)
- SOURCE:
- CYP3A5
Common Searches
Non-Curated Publications
A list of non-curated publications that mention this gene is available.