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Guidelines regarding the use of pharmacogenomic tests in dosing for azothioprine, thioguanine and mercaptopurine have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
Download: article and supplement
Excerpt from the thiopurine dosing guidelines:
Thiopurines are most commonly used to treat nonmalignant conditions but are also critical anticancer agents. The approach to dosing adjustments based on TPMT status may differ depending on the clinical indication and the propensity to initiate therapy at higher vs. lower starting doses. We and others advocate testing for TPMT status prior to initiating thiopurine therapy, so that starting dosages can be adjusted accordingly.
Recommended dosing of azothioprine by TPMT phenotype
| Phenotype (Genotype) | Examples of diplotypes | Implications for azathioprine pharmacologic measures | Dosing recommendations for azothioprine | Classification of recommendations |
|---|---|---|---|---|
| Homozygous wild-type or normal, high activity (two functional *1 alleles) | *1/*1 | Lower concentrations of TGN metabolites, higher methylTIMP, this is the "normal" pattern | Start with normal starting dose (e.g., 2-3 mg/kg/d) and adjust doses of azathioprine based on disease-specific guidelines. Allow 2 weeks to reach steady state after each dose adjustment. | Strong |
| Heterozygote or intermediate activity (one functional allele - *1, plus one nonfunctional allele - *2, *3A, *3B, *3C, or *4) | *1/*2, *1/*3A, *1/*3B, *1/*3C, *1/*4 | Moderate to high concentrations of TGN metabolites; low concentrations of methylTIMP | If disease treatment normally starts at the "full dose", consider starting at 30-70% of target dose (e.g., 1-1.5 mg/kg/d), and titrate based on tolerance. Allow 2-4 weeks to reach steady state after each dose adjustment. | Strong |
| Homozygous variant, mutant, low, or deficient activity (two nonfunctional alleles - *2, *3A, *3B, *3C, or *4) | *3A/*3A, *2/*3A, *3C/*3A, *3C/*4, *3C/*2, *3A/*4 | Extremely high concentrations of TGN metabolites; fatal toxicity possible without dose decrease; no methylTIMP metabolites | Consider alternative agents. If using azathioprine start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady state after each dose adjustment. Azathioprine is the likely cause of myelosuppression. | Strong |
Guidelines regarding the use of pharmacogenomic tests in dosing for azothioprine, thioguanine and mercaptopurine have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
Download: article and supplement
Excerpt from the thiopurine dosing guidelines:
Thiopurines are most commonly used to treat nonmalignant conditions but are also critical anticancer agents. The approach to dosing adjustments based on TPMT status may differ depending on the clinical indication and the propensity to initiate therapy at higher vs. lower starting doses. We and others advocate testing for TPMT status prior to initiating thiopurine therapy, so that starting dosages can be adjusted accordingly.
Recommended dosing of mercaptopurine by TPMT phenotype
| Phenotype (Genotype) | Examples of diplotypes | Implications for mercaptopurine and azathioprine pharmacologic measures | Dosing recommendations for mercaptopurine | Classification of recommendations |
|---|---|---|---|---|
| Homozygous wild-type or normal, high activity (two functional *1 alleles) | *1/*1 | Lower concentrations of TGN metabolites, higher methylTIMP, this is the "normal" pattern | Start with normal starting dose (e.g., 75 mg/m2/d or 1.5 mg/kg/d) and adjust doses of mercaptopurine (and of any other myelosuppressive therapy) without any special emphasis on mercaptopurine compared to other agents. Allow 2 weeks to reach steady state after each dose adjustment. | Strong |
| Heterozygote or intermediate activity (one functional allele - *1, plus one nonfunctional allele - *2, *3A, *3B, *3C, or *4) | *1/*2, *1/*3A, *1/*3B, *1/*3C, *1/*4 | Moderate to high concentrations of TGN metabolites; low concentrations of methylTIMP | Start with reduced doses (start at 30-70% of full dose: e.g., at 50 mg/m2/d or 0.75 mg/kg/d) and adjust doses of MP based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady state after each dose adjustment. In those who require a dosage reduction based on myelosuppression, the median dose may be ~40% lower (44 mg/m2) than that tolerated in wild-type patients (75 mg/m2). In setting of myelosuppression, and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents. | Strong |
| Homozygous variant, mutant, low, or deficient activity (two nonfunctional alleles - *2, *3A, *3B, *3C, or *4) | *3A/*3A, *2/*3A, *3C/*3A, *3C/*4, *3C/*2, *3A/*4 | Extremely high concentrations of TGN metabolites; fatal toxicity possible without dose decrease; no methylTIMP metabolites | For malignancy, start with drastically reduced doses (reduce daily dose by 10-fold and reduce frequency to thrice weekly instead of daily, e.g., 10 mg/m2/d given just 3 days/week) and adjust doses of MP based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady state after each dose adjustment. In setting of myelosuppression, emphasis should be on reducing mercaptopurine over other agents. For nonmalignant conditions, consider alternative nonthiopurine immunosuppressant therapy. | Strong |
Guidelines regarding the use of pharmacogenomic tests in dosing for azothioprine, thioguanine and mercaptopurine have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
Download: article and supplement
Excerpt from the thiopurine dosing guidelines:
Thiopurines are most commonly used to treat nonmalignant conditions but are also critical anticancer agents. The approach to dosing adjustments based on TPMT status may differ depending on the clinical indication and the propensity to initiate therapy at higher vs. lower starting doses. We and others advocate testing for TPMT status prior to initiating thiopurine therapy, so that starting dosages can be adjusted accordingly.
Recommended dosing of thioguanine by TPMT phenotype
| Phenotype (Genotype) | Examples of diplotypes | Implications for pharmacologic measures after thioguanine | Dosing recommendations for thioguanine | Classification of recommendations |
|---|---|---|---|---|
| Homozygous wild-type or normal, high activity (two functional *1 alleles) | *1/*1 | Lower concentrations of TGN metabolites, but note that TGN after thioguanine are 5-10x higher than TGN after mercaptopurine or azathioprine | Start with normal starting dose. Adjust doses of thioguanine and of other myelosuppressive therapy without any special emphasis on thioguanine . Allow 2 weeks to reach steady state after each dose adjustment. | Strong |
| Heterozygote or intermediate activity (one functional allele - *1, plus one nonfunctional allele - *2, *3A, *3B, *3C, or *4) | *1/*2, *1/*3A, *1/*3B, *1/*3C, *1/*4 | Moderate to high concentrations of TGN metabolites; but note that TGN after thioguanine are 5-10x higher than TGN after mercaptopurine or azathioprine | Start with reduced doses (reduce by 30-50%) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady state after each dose adjustment. In setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thioguanine over other agents. | Medium |
| Homozygous variant, mutant, low, or deficient activity (two nonfunctional alleles - *2, *3A, *3B, *3C, or *4) | *3A/*3A, *2/*3A, *3C/*3A, *3C/*4, *3C/*2, *3A/*4 | Extremely high concentrations of TGN metabolites; fatal toxicity possible without dose decrease | Start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady state after each dose adjustment. In setting of myelosuppression, emphasis should be on reducing thioguanine over other agents. For nonmalignant conditions, consider alternative nonthiopurine immunosuppressant therapy. | Strong |
The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for azathioprine based on TPMT genotype (PMID:21412232). They recommend selecting an alternative drug or reducing the initial dose for patients carrying inactive alleles.
| Phenotype (Genotype) | Therapeutic Dose Recommendation | Level of Evidence | Clinical Relevance |
|---|---|---|---|
| IM (one inactive allele: *2, *3, *4-*18) | Select alternative drug or reduce dose by 50%. Increase dose in response of hematologic monitoring and efficacy. | 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): Failure of lifesaving therapy e.g. anticipated myelosuppression; prevention of breast cancer relapse; arrhythmia; neutropenia < 0.5x109/l; leucopenia < 1.0x109/l; thrombocytopenia < 25x109/l; life-threatening complications from diarrhea. |
| PM (two inactive alleles: *2, *3, *4-*18) | Select alternative drug or reduce dose by 90%. Increase dose in response of hematologic monitoring and efficacy. | 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): death; arrhythmia; unanticipated myelosuppression. |
- *See Methods or PMID: 18253145 for definition of "good quality."
- S: statistically significant difference.
The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for mercaptopurine based on TPMT genotype (PMID:21412232). They recommend selecting an alternative drug or reducing the initial dose for patients carrying inactive alleles.
| Phenotype (Genotype) | Therapeutic Dose Recommendation | Level of Evidence | Clinical Relevance |
|---|---|---|---|
| IM (one inactive allele: *2, *3, *4-*18) | Select alternative drug or reduce dose by 50%. Increase dose in response of hematologic monitoring and efficacy. | 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): Failure of lifesaving therapy e.g. anticipated myelosuppression; prevention of breast cancer relapse; arrhythmia; neutropenia < 0.5x109/l; leucopenia < 1.0x109/l; thrombocytopenia < 25x109/l; life-threatening complications from diarrhea. |
| PM (two inactive alleles: *2, *3, *4-*18) | Select alternative drug or reduce dose by 90%. Increase dose in response of hematologic monitoring and efficacy. | 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): death; arrhythmia; unanticipated myelosuppression. |
- *See Methods or PMID: 18253145 for definition of "good quality."
- S: statistically significant difference.
The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for thioguanine based on TPMT genotype (PMID:21412232). They recommend selecting an alternative drug for patients carrying inactive alleles.
| Phenotype (Genotype) | Therapeutic Dose Recommendation | Level of Evidence | Clinical Relevance |
|---|---|---|---|
| IM (one inactive allele: *2, *3, *4-*18) | Select alternative drug. Insufficient data to allow calculation of dose adjustment. | Published controlled studies of moderate 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. |
| PM (two inactive alleles: *2, *3, *4-*18) | Select alternative drug. Insufficient data to allow calculation of dose adjustment. | Published case reports, well documented, and having relevant pharmacokinetic or clinical endpoints. Well documented case series. | Clinical effect (S): death; arrhythmia; unanticipated myelosuppression. |
- *See Methods or PMID: 18253145 for definition of "moderate" quality.
- S: statistically significant difference.
Information regarding PGx on FDA drug labels is derived from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels". Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.
The FDA recommends, but does not require genetic or phenotypic testing for TPMT.
Excerpt from the azathioprine drug label:
"It is recommended that consideration be given to either genotype or phenotype patients for TPMT."
Patients with low or absent TPMT activity who are treated with conventional doses of azathioprine are at increased risk for severe, life-threatening myelosuppression resulting from treatment with azathioprine. Patients with intermediate TPMT activity may be at increased risk of myelotoxicity when given conventional azathioprine doses. Physicians may consider alternative therapies for patients homozygous for non-functional TPMT alleles(most commonly associated with the alleles TPMT*2, TPMT*3A, and TPMT*3C), and dose reduction is recommended for heterozygous patients with reduced TPMT activity. Approximately 10% of Caucasians and African Americans carry one non-functional TPMT allele and exhibit intermediate TPMT activity, while 0.3% are homozygous for non-functional TPMT alleles, yielding low or absent TPMT activity.
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Azathioprine drug label.
Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*
Although the cisplatin drug label does not specifically mention genetic testing, the FDA highlight warnings and precautions when treating children who have certain TPMT gene variants due to an increased risk of ototoxicity.
Excerpt from the cisplatin drug label:
"Certain genetic variants in the thiopurine S-methyltransferase gene (e.g., TPMT*3B and TPMT*3C) are associated with an increased risk of ototoxicity in children administered conventional doses of cisplatin." The label refers to a study in children that found an association between TPMT gene variants and ototoxicity: [Article:19898482].
"Children who do not have one of these TPMT gene variants remain at risk for ototoxicity. All pediatric patients receiving cisplatin should have audiometric testing at baseline, prior to each subsequent dose, of drug and for several years post therapy."
SUMMARY
The FDA label highlights warnings and precautions for cisplatin treatment in children with certain TPMT gene variants, due to an increased risk of ototoxicity. The FDA states that all children undergoing cisplatin treatment have a risk of ototoxicity, and all children should undergo audiometric testing.
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Cisplatin drug label PDF.
*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.
The pharmacogenomic relationship between mercaptopurine and TPMT is well described. See the TPMT VIP and Thiopurines Pathway for more details. Recent work by the Clinical Pharmacogenomics Implementation Consortium (CPIC) has published guidelines for dosing of mercaptopurine in individuals with TPMT variants.
The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Mercaptopurine.
Excerpt from the Mercaptopurine drug label:
"Mercaptopurine is inactivated via two major pathways. One is thiol methylation, which is catalyzed by the polymorphic enzyme thiopurine S-methyltransferase (TPMT), to form the inactive metabolite methyl-6-MP. TPMT activity is highly variable in patients because of a genetic polymorphism in the TPMT gene. For Caucasians and African Americans, approximately 0.3% (1:300) of patients have two non-functional alleles (homozygous-deficient) of the TPMT gene and have little or no detectable enzyme activity. Approximately 10% of patients have one TPMT non-functional allele (heterozygous) leading to low or intermediate TPMT activity and 90% of individuals have normal TPMT activity with two functional alleles. Homozygous-deficient patients (two non-functional alleles), if given usual doses of mercaptopurine, accumulate excessive cellular concentrations of active thioguanine nucleotides predisposing them to mercaptopurine toxicity (see WARNINGS and PRECAUTIONS). Heterozygous patients with low or intermediate TPMT activity accumulate higher concentrations of active thioguanine nucleotides than people with normal TPMT activity and are more likely to experience mercaptopurine toxicity (see WARNINGS and PRECAUTIONS). TPMT genotyping or phenotyping (red blood cell TPMT activity) can identify patients who are homozygous deficient or have low or intermediate TPMT activity."
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Mercaptopurine drug label.
*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.
The pharmacogenomic releationship between thioguanine and TPMT is well described. See the TPMT VIP and Thiopurines Pathway for more details. Recent work by the Clinical Pharmacogenomics Implementation Consortium (CPIC) has published guidelines for dosing of thioguanine in individuals with TPMT variants.
The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Thioguanine.
Excerpt from the Thioguanine (Tabloid) drug label:
"There are individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) who may be unusually sensitive to the myelosuppressive effects of thioguanine and prone to developing rapid bone marrow suppression following the initiation of treatment. Substantial dosage reductions may be required to avoid the development of life-threatening bone marrow suppression in these patients. Prescribers should be aware that some laboratories offer testing for TPMT deficiency. Since bone marrow suppression may be associated with factors other than TPMT deficiency, TPMT testing may not identify all patients at risk for severe toxicity. Therefore, close monitoring of clinical and hematologic parameters is important. Bone marrow suppression could be exacerbated by coadministration with drugs that inhibit TPMT, such as olsalazine, mesalazine, or sulphasalazine."
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Thioguanine (Tabloid) drug label.
*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.
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 ? |
||
|---|---|---|---|---|---|
| rs1800460 |
To see relevance please register or sign in. |
1 | |||
| rs1800462 |
To see relevance please register or sign in. |
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.
A non-comprehensive list of genetic tests for specific variants, including descriptions of and links to individual tests; 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.
| PGx Test | Variants Assayed | Related Drugs? |
|---|---|---|
| Prometheus TPMT Genetics | Not available | |
| TPMT GenotypR | rs1142345, rs1800460, rs1800462 |
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 |
|
|---|---|---|---|---|---|---|
| rs1142345 | TPMT*3C, c.719A>G, g.18070918T>C, g.18238897T>C, g.29457A>G, p.Tyr240Cys |
T > C
|
Missense |
Tyr240Cys
|
||
| rs12201199 | TPMT:rs12201199 A/T, c.419+94T>A, g.18079802A>T, g.20573T>A |
A > T
|
Intronic | |||
| rs1800460 | TPMT*3B, c.460G>A, g.18079228C>T, g.18247207C>T, g.21147G>A, p.Ala154Thr |
C > T
|
Missense |
Ala154Thr
|
||
| rs1800462 | TPMT*2, TPMT:238G>C, c.238G>C, g.16420G>C, g.18083955C>G, g.18251934C>G, p.Ala80Pro |
C > G
|
Missense |
Ala80Pro
|
||
| rs1800584 | TPMT*4, c.626-1G>A, g.18071012C>T, g.29363G>A |
C > T
|
5' Flanking |
Overview
| Alternate Names: | OTTHUMP00000016076; S-adenosyl-L-methionine:thiopurine S-methyltransferase; thiopurine methyltransferase |
|---|---|
| Alternate Symbols: | None |
| Haplotypes: | TPMT*1; TPMT*2; TPMT*3A; TPMT*3B; TPMT*3C; TPMT*3D; TPMT*3E; TPMT*4; TPMT*5; TPMT*6; TPMT*7; TPMT*8; TPMT*9; TPMT*10; TPMT*11; TPMT*12; TPMT*13; TPMT*14; TPMT*15; TPMT*16; TPMT*17; TPMT*18; TPMT*21; TPMT*22; TPMT*23; TPMT*25; TPMT*20(PMID:16917910); TPMT*20(PMID:16946561); TPMT*24(PMID: 18602085); TPMT*24(PMID: 18708949) |
| PharmGKB Accession Id: | PA356 |
Details
| Cytogenetic Location: | chr6 : p22.3 - p22.3 |
|---|---|
| GP mRNA Boundary†: | chr6 : 18128542 - 18155374 |
| GP Gene Boundary†: | chr6 : 18125542 - 18165374 |
| Strand: | minus |
| Product Name: | No data available |
All alleles are displayed on the positive chromosomal strand.
| Haplotype | rs1142345 | rs12529220 | rs17839843 | rs1800460 | rs1800462 | rs1800584 | rs2518463 | rs2842934 | rs3931660 |
|---|---|---|---|---|---|---|---|---|---|
| TPMT*1 | T | T | A | C | C | C | A | A | A |
| TPMT*2 | T | T | A | C | G | C | A | A | A |
| TPMT*3A | C | T | A | T | C | C | A | A | A |
| TPMT*3B | T | T | A | T | C | C | A | A | A |
| TPMT*3C | C | T | A | C | C | C | A | A | A |
| TPMT*3D | C | T | A | T | C | C | A | A | A |
| TPMT*3E | C | A | G | T | C | C | G | G | T |
| TPMT*4 | T | T | A | C | C | T | A | A | A |
| TPMT*5 | T | T | A | C | C | C | A | A | A |
| TPMT*6 | T | T | A | C | C | C | A | A | A |
| TPMT*7 | T | T | A | C | C | C | A | A | A |
| TPMT*8 | T | T | A | C | C | C | A | A | A |
| TPMT*9 | T | T | A | C | C | C | A | A | A |
| TPMT*10 | T | T | A | C | C | C | A | A | A |
| TPMT*11 | T | T | A | C | C | C | A | A | A |
| TPMT*12 | T | T | A | C | C | C | A | A | A |
| TPMT*13 | T | T | A | C | C | C | A | A | A |
| TPMT*14 | T | T | A | C | C | C | A | A | A |
| TPMT*15 | T | T | A | C | C | C | A | A | A |
| TPMT*16 | T | T | A | C | C | C | A | A | A |
| TPMT*17 | T | T | A | C | C | C | A | A | A |
| TPMT*18 | T | T | A | C | C | C | A | A | A |
| TPMT*21 | T | T | A | C | C | C | A | A | A |
| TPMT*22 | T | T | A | C | C | C | A | A | A |
| TPMT*23 | T | T | A | C | C | C | A | A | A |
| TPMT*25 | T | T | A | C | C | C | A | A | A |
| TPMT*20(PMID:16917910) | T | T | A | C | C | C | A | A | A |
| TPMT*20(PMID:16946561) | T | T | A | C | C | C | A | A | A |
| TPMT*24(PMID: 18602085) | T | T | A | C | C | C | A | A | A |
| TPMT*24(PMID: 18708949) | T | T | A | C | C | C | A | A | A |
PharmGKB Curated Pathways
Pathways created internally by PharmGKB based primarily on literature evidence.
External Pathways
Links to non-PharmGKB pathways.
Curated Information ?
| Evidence | Drug |
|---|---|
| azathioprine | |
| cisplatin | |
| mercaptopurine | |
| s-adenosylmethionine | |
| thioguanine |
| Evidence | Drug Class |
|---|---|
| purine analogues |
Curated Information ?
Publications related to TPMT: 112
Datasets
- Analysis of variation in mouse TPMT expression and activity.
- Gene expression in ALL cells correlating with GSTM1 deletion germline genotype
- Pharmacogenetic Risk Factors for Osteonecrosis of the Hip Among Children With Leukemia
- Genetic Polymorphism of Inosine Triphosphate Pyrophosphatase Is a Determinant of Mercaptopurine Metabolism and Toxicity During Treatment for Acute Lymphoblastic Leukemia
- Genotype data for Mouse TPMT
- Karyotypic abnormalities create discordance of germline genotype and cancer cell phenotypes
- Pharmacogenetics of Minimal Residual Disease Response in Children with B-Precursor Acute Lymphoblastic Leukemia (ALL): A Report from the Children's Oncology Group
- TGN and MeTIMP in ALL patients
- TPMT Activity in Hapmap Cell Lines (CEPH)
LinkOuts
- UniProtKB:
- TPMT_HUMAN (P51580)
- Q9BS45_HUMAN (Q9BS45)
- Ensembl:
- ENSG00000137364
- GenAtlas:
- TPMT
- GeneCard:
- GC06M018186 (7172)
- MutDB:
- TPMT
- ALFRED:
- LO206732U