Gene:
TPMT
thiopurine S-methyltransferase

Available Guidelines

  1. CPIC Dosing Guideline for azathioprine and TPMT
  2. CPIC Dosing Guideline for mercaptopurine and TPMT
  3. CPIC Dosing Guideline for thioguanine and TPMT
  4. Dutch Pharmacogenetics Working Group Guideline for azathioprine and TPMT
  5. Dutch Pharmacogenetics Working Group Guideline for mercaptopurine and TPMT
  6. Dutch Pharmacogenetics Working Group Guideline for thioguanine and TPMT

last updated 01/17/2013

CPIC Dosing Guideline for azathioprine and TPMT

Summary

Consider an alternate agent or extreme dose reduction of azathioprine for patients with low or deficient TPMT activity. Start at 30-70% of target dose for patients with intermediate enzyme activity.

There's more of this guideline. Read more.


last updated 01/17/2013

CPIC Dosing Guideline for mercaptopurine and TPMT

Summary

Start with reduced doses of mercaptopurine for patients with one nonfunctional TPMT allele, or drastically reduced doses for patients with malignancy and two nonfunctional alleles; adjust dose based on degree of myelosuppression and disease-specific guidelines. Consider alternative nonthiopurine immunosuppressant therapy for patients with nonmalignant conditions and two nonfunctional alleles.

There's more of this guideline. Read more.


last updated 01/17/2013

CPIC Dosing Guideline for thioguanine and TPMT

Summary

Start with reduced doses of thioguanine for patients with one nonfunctional TPMT allele, or drastically reduced doses for patients with malignancy and two nonfunctional alleles; adjust dose based on degree of myelosuppression and disease-specific guidelines. Consider alternative nonthiopurine immunosuppressant therapy for patients with nonmalignant conditions and two nonfunctional alleles.

There's more of this guideline. Read more.





PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



last updated 10/25/2013

FDA Label for azathioprine and TPMT

This label is on the FDA Biomarker List
Genetic testing recommended

Summary

The azathioprine (Imuran) FDA-approved drug label recommends testing for TPMT genotype or phenotype to identify patients who are at increased risk of myelotoxicity: those with low or absent TPMT activity. The label also recommends a further reduced dosage or alternative therapies in patients with low or absent TPMT activity treated with azathioprine and allopurinol concomitantly.

There's more of this label. Read more.


last updated 10/25/2013

FDA Label for cisplatin and TPMT

This label is on the FDA Biomarker List
Actionable PGx

Summary

The FDA-approved drug label for cisplatin (PLATINOL) highlights warnings and precautions when treating children with certain TPMT gene variants (e.g., TPMT *3B and TPMT *3C) due to an increased risk of ototoxicity. The drug label states that all children undergoing cisplatin (PLATINOL) treatment have a risk of ototoxicity, and all children should undergo audiometric testing.

There's more of this label. Read more.


last updated 10/25/2013

FDA Label for thioguanine and TPMT

This label is on the FDA Biomarker List
Actionable PGx

Summary

The drug label recommends substantial dosage reductions for individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) 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.

There's more of this label. Read more.


European Medicines Agency (EMA) Label for mercaptopurine and TPMT

Actionable PGx

Summary

The EMA European Public Assessment Report (EPAR) for mercaptopurine (Xaluprine) contains information regarding its metabolism by TPMT, and that patients with reduced activity are at increased risk of severe toxicity and likely require a reduced dose. TPMT genotyping or phenotyping can be used to identify these patients, although this should not replace close monitoring of blood counts.

There's more of this label. Read more.


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.

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.

? = Mouse-over for quick help

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?
DMET Plus (Affymetrix, Inc) Variant in TPMT
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 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
No VIP available CA VA *1 N/A N/A N/A
No VIP available No VIP available VA *1S N/A N/A N/A
No VIP available CA VA *2 N/A N/A N/A
No VIP available CA VA *3A N/A N/A N/A
No VIP available CA VA *3B N/A N/A N/A
No VIP available CA VA *3C N/A N/A N/A
No VIP available No VIP available VA *3D N/A N/A N/A
No VIP available No VIP available VA *3E N/A N/A N/A
No VIP available No VIP available VA *4 N/A N/A N/A
No VIP available No VIP available VA *5 N/A N/A N/A
No VIP available No VIP available VA *6 N/A N/A N/A
No VIP available No VIP available VA *7 N/A N/A N/A
No VIP available No VIP available VA *8 N/A N/A N/A
No VIP available No VIP available VA *9 N/A N/A N/A
No VIP available No VIP available VA *10 N/A N/A N/A
No VIP available No VIP available VA *12 N/A N/A N/A
No VIP available No VIP available VA *13 N/A N/A N/A
No VIP available No VIP available VA *14 N/A N/A N/A
No VIP available No VIP available VA *16 N/A N/A N/A
No VIP available No VIP available VA *17 N/A N/A N/A
No VIP available No VIP available VA *18 N/A N/A N/A
No VIP available No VIP available VA *19 N/A N/A N/A
No VIP available No VIP available VA *21 N/A N/A N/A
No VIP available No VIP available VA *22 N/A N/A N/A
No VIP available No VIP available VA *24 N/A N/A N/A
No VIP available No VIP available VA *25 N/A N/A N/A
rs1142345 18070918T>C, 18130918T>C, 29457A>G, 719A>G, TPMT*3C, Tyr240Cys
T > C
Missense
Tyr240Cys
No VIP available CA VA
rs12201199 18079802A>T, 18139802A>T, 20573T>A, 419+94T>A, TPMT:rs12201199 A/T
A > T
Intronic
No VIP available No Clinical Annotations available VA
rs12529220 12128A>T, 141-101A>T, 18088247T>A, 18148247T>A
T > A
Intronic
No VIP available No Clinical Annotations available VA
rs151149760
T > G
Missense
Lys119Thr
No VIP available No Clinical Annotations available VA
rs17839843 16521C>T, 18083854G>A, 18143854G>A, 339C>T, Thr113=
G > A
Synonymous
Thr113Thr
rs1800460 18079228C>T, 18139228C>T, 21147G>A, 460G>A, Ala154Thr, TPMT*3B
C > T
Missense
Ala154Thr
rs1800462 16420G>C, 18083955C>G, 18143955C>G, 238G>C, Ala80Pro, TPMT*2, TPMT:238G>C
C > G
Missense
Ala80Pro
rs1800584 18071012C>T, 18131012C>T, 29363G>A, 626-1G>A, TPMT*4
C > T
Acceptor
No VIP available No Clinical Annotations available VA
rs2518463 16606T>C, 18083769A>G, 18143769A>G, 366+58T>C
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs2842934 18079214G>A, 18139214G>A, 21161C>T, 474C>T, Ile158=
G > A
Synonymous
Ile158Ile
No VIP available No Clinical Annotations available VA
rs2842949 18074021C>A, 18134021C>A, 26354G>T, 580+14G>T
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs3931660 11270T>A, 140+114T>A, 18089105A>T, 18149105A>T
A > T
Intronic
No VIP available No Clinical Annotations available VA
rs4449636 12356C>T, 18088019G>A, 18148019G>A, 233+35C>T
G > A
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  None
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
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.

Thiopurine S-methyltransferase (TPMT; S-adenosyl-L-methionine:thiopurine S-methyltransferase; EC 2.1.1.67) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP) and azathioprine as well as other aromatic and heterocyclic sulfhydryl compounds [Articles:13981612, 6838629].

Weinshilboum and Sladek (1980) [Article:7191632] reported trimodality for level of red cell TPMT among 298 randomly selected Caucasian subjects: 88.6% had high enzyme activity; 11.1% had intermediate activity and 0.3% had undetectable activity. This distribution conformed to Hardy-Weinberg expectations for a pair of autosomal codominant alleles for low and high activity, TPMT-L and TPMT-H, with frequencies of 0.059 and 0.941, respectively. Segregation analysis was consistent with this hypothesis. This genetic polymorphism has been shown to be an important factor in individual variations in response to thiopurine drug therapy. 6-MP is inactivated, in part, by S-methylation, catalyzed by TPMT. An alternative "metabolic activation" process leads to the formation of cytotoxic 6-thioguanine nucleotides (6-TGN). In addition, 6-MP is metabolized to methyl-thioinosine monophosphate, which inhibits de novo purine synthesis, adding another mechanism of cytotoxicity [Articles:4328325, 14576848].

Lennard et al. (1987, 1990) [Articles:3467886, 1973780] showed that, in the children with acute lymphoblastic leukemia (ALL) who were treated with 6-MP, red cell 6-TGN correlated inversely with RBC TPMT activity ( i.e., the lower the level of S-methylation, the more drug would be available for metabolism to form the cytotoxic 6-TGNs). It was also demonstrated that subjects with very low RBC (red blood cell) TPMT ( i.e., those homozygous for that trait) were at greatly increased risk for life-threatening myelosuppression when they were treated with "standard" doses of thiopurine drugs [Articles:2758725, 1960624]. Conversely, patients with ALL who had 6-TGN concentrations below the group mean had higher TPMT activities and a higher subsequent relapse rate. Individuals heterozygous for functional variants exhibited intermediate tolerance of 6-MP (i.e. intermediate between that observed for homozygous deficient and homozygous wildtype patients [Article:11304783]). RBC TPMT levels have been found to correlate with levels in other tissues such as liver, kidney, and lymphocytes [Articles:7138494, 1306116]. Therefore, the TPMT genetic polymorphism is a significant factor responsible for serious adverse drug reactions (myelosuppression) in patients treated with thiopurines and may also contribute to individual variation in therapeutic efficacy [Article:15784872].TPMT has become one of a small number of examples in pharmacogenomics to be "translated" into routine clinical care.

The human TPMT gene is 34 kb in length, consists of 10 exons, maps to chromosome 6p22.3 [Article:8561894] and has a pseudogene located on chromosome 18 [Article:7628307]. 28 variant alleles have been identified [Article:18602085], most of which have been associated with decreased activity in vitro [Article:18708949]. Most of these involve nonsynonymous SNPs [Articles:16220112, 18708949]. Among those, TPMT*2,*3A,*3B, and *3C have been intensively studied both with regard to their clinical implications and/or molecular mechanisms. Szumlanski et al. (1996) [Article:8561894] and Tai et al. (1996) [Article:8644731] described TPMT*3A (OMIM 187680.0002), the most common variant allele associated with low TPMT activity in Caucasians (frequency approximately 5%). TPMT*3A contains two nonsynonymous cSNPs, one in exon 7 and another in exon 10, that result in Ala154Thr and Tyr240Cys alterations in encoded amino acids. TPMT*3B occurs rarely and contains only the exon 7 SNP while TPMT*3C contains only the exon 10 SNP and is the most common variant allele in East Asian and African American populations (frequency approximately 2%). More extensive population testing shows that *8 also appears at a frequency of approximately 2% in some African populations [Article:17473918].

TPMT*2, the first variant allele described, results in an Ala80Pro amino acid substitution (*2; OMIM 187680.0001) [Article:7862671]. This allele is much less common than either TPMT*3A or *3C. It was also shown that expression of TPMT*2 and *3A were comparable in wild-type and mutant cDNA s, but wild-type had an \~100 fold higher enzymatic activity than mutant TPMT [Article:9177237]. Gene expression did not correlate with protein activity in TPMT*2 and *3 [Articles:7862671, 9177237]. Tai et al. (1997) [Article:9177237] showed that enhanced degradation of TPMT allozymes encoded by the TPMT*2 and TPMT*3A alleles is the mechanism for decreased levels of TPMT protein and catalytic activity inherited as a result of these alleles.

Subsequent studies performed by Wang et al. (2003, 2005) [Articles:12972954, 15967990] demonstrated that the rapid degradation of TPMT *3A involves molecular chaperones such as the heat shock proteins hsp70 and hsp90 and that TPMT*3A can also form intracellular aggresomes; both processes contribute to the low levels of protein and activity observed in the tissues of subjects with this allele.

This series of observations suggested that a dynamic balance might exist among TPMT*3A protein folding, protein degradation and protein aggregation and raised the question of the identity of the proteins involved in these cellular processes. In an effort to answer that question, a Saccharomyces cerevisiae yeast gene-deletion library was used to identify genes required for the degradation/aggregation of TPMT*3A (Li et al. (2008) [Article:18820593]). Twenty-four genes that fell into several functionally-related categories were identified. The classes of genes involved included those affecting ubiquitin-dependent protein degradation (E2 ubiquitin conjugating enzymes, E3 ubiquitin ligases and proteasome subunits), vesicle trafficking and vacuolar (lysosomal) degradation. The presence of genes involved in vesicular transport and vacuolar degradation suggested a possible role for autophagy in TPMT*3A degradation. UBE2G2, the human homologue of the E2 ubiquitin conjugating enzyme identified by the yeast genetic screen, was demonstrated to be involved in the degradation of TPMT*3A in mammalian cells. Further, expression of TPMT*3A -induced autophagy and small interfering RNA-mediated knockdown of the expression of AGT7, an autophagy-related gene, enhanced TPMT*3A aggregation in mammalian cells, indicating that autophagy is also involved in TPMT*3A degradation.

TPMT*4 and *15 involve alterations in canonical mRNA splice site sequences [Articles:15083071, 9486974], resulting in alternative TPMT mRNA splicing and decreased enzyme expression.

Recently, trinucleotide repeat variants in the TPMT promoter region have been described which may explain the 1-2% of Caucasians who demonstrate ultra-metabolizer phenotype [Article:18408566]. Also, a promoter region VNTR (Variable Number Tandem Repeat) which may have functional significance has been investigated [Articles:10376766, 11503011, 10612847, 10976552, 12563179].

All of the SNPs associated with low TPMT activity have different allele frequencies among various ethnic groups. TPMT*3A is the most common allele in Caucasians, with a frequency about 5%. TPMT*3C is the most common allele in African American and East Asian populations [Articles:9931346, 9931345, 10634140, 10208641], though a recent report indicates that TPMT*8 may be more common in African populations than has been previously thought [Article:17473918].

The variant alleles *3A, *3B, *3C and *2 result in significant decreases in levels of TPMT protein and, therefore, enzyme activity [Articles:8561894, 8644731, 7862671, 9177237, 11304783]. *4 results in a truncated protein and is associated with decreased enzyme activity [Article:9486974] . *3A, *3B, *3C and *2 are associated with thiopurine drug-related toxicity (myelosuppression), which is associated with increased RBC 6-TGN levels and bone marrow suppression after treatment with standard doses of thiopurine drugs [Articles:2758725, 1960624].

Thiopurine therapy plays a role in the treatment of autoimmune diseases, inflammatory bowel diseases, lupus, transplantation [Article:1451710], and acute lymphoblastic leukemia.

Note: The TPMT 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 Very important pharmacogene summary: thiopurine S-methyltransferase. Pharmacogenetics and genomics. 2010. Wang Liewei, Pelleymounter Linda, Weinshilboum Richard, Johnson Julie A, Hebert Joan M, Altman Russ B, Klein Teri E. PubMed
History

Submitted by Liewei Wang, Linda Pelleymounter, Richard Weinshilboum, Julie A. Johnson(PPII)

Updated by Joan M. Hebert

Variant Summaries rs1142345, rs1800460, rs1800462, rs1800584
Haplotype Summaries TPMT:*3A
Drugs
Diseases

Appendix

Other Variants of Known or Suspected Functional Significance

(For additional alleles, please refer to the TPMT Nomenclature Committee and [Article:23407052])

Allele
Common Name(s)
Variant Information
TPMT*3D 292G>T+460G>A+719A>G (Glu98Stop+Ala154Thr+Tyr240Cys) Identified in a clinical sample demonstrating intermediate TPMT activity [Article:9246020].
TPMT*5 146T>C(Leu49Ser) Present in a patient (*1/*5) demonstrating intermediate TPMT activity [Article:9246020]. When *5 was expressed in COS-1 cells, enzyme activity level was almost undetectable [Article:16220112].
TPMT*6 539A>T(Tyr180Phe) Present in a Korean subject demonstrating low RBC TPMT activity [Article:9246020]. When *6 was expressed in COS-1 cells, enzyme activity level was about a third of wild-type [Article:16220112].
TPMT*7 681T>G(His227Gln) First detected in a European subject (*1/*7) who was an intermediate methylator [Article:9711875]. Present in a European patient (*1/*7) treated with azathiopurine who developed severe leukopenia. In a recombinant yeast expression system, intrinsic clearance rate for the *7 allele was about 10-fold lower than that for *1 [Article:13679074]. In another report, enzyme activity when expressed in COS-1 cells was essentially at wild-type level [Article:16220112].
TPMT*8 644G>A(Arg215His) *8 found in one African-American heterozygote (*1/*8) who demonstrated intermediate TPMT activity [Article:9931346].
TPMT*9 356A>C(Lys119Thr) *1/*9 German-Caucasian subject had intermediate TPMT activity [Article:15226673] . Noted in a Caucasian subject with intermediate TPMT activity [Article:18602085]. However, when *9 was expressed in vitro, the catalytic activity of the variant protein was not significantly affected [Articles:16220112, 18602085], and *9 was found in one subject defined as a normal methylator [Article:15226673].
TPMT*10 430G>C(Gly144Arg) Present in a patient (*1/*10) treated with azathiopurine who developed severe leukopenia. In a recombinant yeast expression system, intrinsic clearance rate for the *10 allele was about 3.5-fold lower than that for *1 [Article:13679074]. In another report, expression in COS-1 cells resulted in enzyme activity at about 70% that of wild-type [Article:16220112].
TPMT*11 395G>A(Cys132Tyr) Identified in a patient of Spanish origin (*3A/*11) who demonstrated very low RBC TPMT activity [Article:12835738]. Expression of the *11 allele in COS-1 cells resulted in low enzyme activity [Article:16220112].
TPMT*12 374C>T(Ser125Leu) Present in an azathiopurine-treated patient (*1/*12) who developed severe leukopenia. In a recombinant yeast expression system, intrinsic clearance rate for the *12 allele was about 3.5-fold lower than that for *1 [Article:13679074]. In another report, expression in COS-1 cells resulted in enzyme activity of about 40% of wild-type [Article:16220112].
TPMT*13 83A>T(Glu28Val) Identified in an azathiopurine-treated patient (*1/*13) who developed severe leukopenia. In vitro, enzyme activity for the *13 allele was about 60% that of *1 [Articles:13679074, 16220112].
TPMT*14 1A>G(Met1Val) Identified in a Northern European patient who demonstrated low RBC TPMT activity [Article:15083071].
TPMT*15 intron VII/exon VIII (IVS7-1G>A)(splice site) Identified in a Northern European patient who demonstrated low RBC TPMT activity [Article:15083071].
TPMT*16 488G>A(Arg163His) In vitro, decreased the intrinsic clearance value with respect to 6-TG methylation three-fold. A Morrocan patient (*1/*16) was an intermediate methylator [Article:15652243].*1/*16 German-Caucasian heterozygote had intermediate TPMT activity [Article:15226673].
TPMT*17 124C>G(Gln42Glu) *1/*17 German-Caucasian subject had intermediate TPMT activity [Article:15226673].
TPMT*18 211G>A(Gly71Arg) *1/*18 German-Caucasian subject had intermediate TPMT activity [Article:15226673].
TPMT*20 712A>G (Lys238Glu) Identified in a Caucasian subject with intermediate RBC TPMT activity [Article:16917910].
TPMT*21 205C>G(Leu69Val) Noted in a Caucasian subject with intermediate TPMT activity [Article:16917910]. When *21 was expressed in a recombinant yeast expression system, the resulting enzyme had significantly reduced intrinsic clearance when compared to wild-type protein [Article:18602085].
TPMT*22 488G>C (Arg163Pro) Identified in a Caucasian subject with intermediate RBC TPMT activity [Article:16917910].
TPMT*23 500C>G(Ala167Gly) Identified in a Caucasian subject with very low RBC TPMT activity [Article:17885628].
TPMT*24 537G>T(Gln179His) Identified in a Caucasian subject having intermediate methylator phenotype. However, when *24 was expressed in a recombinant yeast expression system, the catalytic activity of the variant protein was not significantly affected [Article:18602085].
TPMT*25 634T>C (Cys212Arg) Identified in two Caucasian subjects demonstrating intermediate thiopurine drug methylation activity. In a recombinant yeast expression system, the recombinant enzyme had significantly decreased intrinsic clearance rate when compared to wild-type protein [Article:18602085].

Haplotype Overview

The Translational Pharmacogenetics Project (TPP) is a PGRN-led initiative with the goal to operationalize the work of CPIC by translating widely accepted actionable pharmacogenetics discoveries into real-world clinical practice. The group has published on integrating pharmacogenomics into the electronic medical record: A Clinician-Driven Automated System for Integration of Pharmacogenetic Interpretations Into an Electronic Medical Record. Download the TPP file for TPMT here: TPMT lookup table .

TPMT alleles are as determined by the TPMT nomenclature committee [Article:23407052] . Updated on PharmGKB 3/10/2014.

Source: PharmGKB

All alleles in the download file are on the positive chromosomal strand. PharmGKB considers the first haplotype listed in each table as the reference haplotype for that set.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

External Pathways

Links to non-PharmGKB pathways.

  1. Methylation - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Evidence Drug Class
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
purine analogues

Curated Information ?

Publications related to TPMT: 278

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Host thiopurine methyltransferase status affects mercaptopurine antileukemic effectiveness in a murine model. Pharmacogenetics and genomics. 2014. Ramsey Laura B, 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
Prioritizing genomic applications for action by level of evidence: a horizon-scanning method. Clinical pharmacology and therapeutics. 2014. Dotson W 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
Identification of a novel thiopurine S-methyltransferase allele (TPMT*37). Pharmacogenetics and genomics. 2014. Roberts Rebecca L, 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
PG4KDS: A model for the clinical implementation of pre-emptive pharmacogenetics. American journal of medical genetics. Part C, Seminars in medical genetics. 2014. Hoffman James M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Thiopurine pharmacogenomics: association of SNPs with clinical response and functional validation of candidate genes. Pharmacogenomics. 2014. Matimba Alice, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenomic assessment of cisplatin-based chemotherapy outcomes in ovarian cancer. Pharmacogenomics. 2014. Khrunin Andrey V, 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
Challenges in interpreting the evidence for genetic predictors of ototoxicity. Clinical pharmacology and therapeutics. 2013. Ratain M J, 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
Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clinical pharmacology and therapeutics. 2013. Van Driest Sara L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
TPMT genetic variants are associated with increased rejection with azathioprine use in heart transplantation. Pharmacogenetics and genomics. 2013. Liang Jackson J, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Replication of TPMT and ABCC3 Genetic Variants Highly Associated With Cisplatin-Induced Hearing Loss in Children. Clinical pharmacology and therapeutics. 2013. Pussegoda K, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The Role of Inherited TPMT and COMT Genetic Variation in Cisplatin-Induced Ototoxicity in Children With Cancer. Clinical pharmacology and therapeutics. 2013. Yang J J, 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
Understanding platinum-induced ototoxicity. Trends in pharmacological sciences. 2013. Langer Thorsten, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Thiopurine methyltransferase genotype-phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia. British journal of clinical pharmacology. 2013. Lennard Lynne, 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
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Polymorphisms influencing olanzapine metabolism and adverse effects in healthy subjects. Human psychopharmacology. 2013. Cabaleiro Teresa, et al. PubMed
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New genetic associations in thiopurine-related bone marrow toxicity among inflammatory bowel disease patients. Pharmacogenomics. 2013. Zabala William, et al. PubMed
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Nomenclature for alleles of the thiopurine methyltransferase gene. Pharmacogenetics and genomics. 2013. Appell Malin L, et al. PubMed
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Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy. Pharmacogenomics. 2013. Weng Liming, et al. PubMed
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Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update. Clinical pharmacology and therapeutics. 2013. Relling M V, et al. PubMed
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A new thiopurine s-methyltransferase haplotype associated with intolerance to azathioprine. Journal of clinical pharmacology. 2013. Colleoni Lara, et al. PubMed
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Pharmacogenomics of acute lymphoid leukemia: new insights into treatment toxicity and efficacy. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program. 2013. Relling Mary V, et al. PubMed
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A Clinician-Driven Automated System for Integration of Pharmacogenetic Interpretations Into an Electronic Medical Record. Clinical pharmacology and therapeutics. 2012. Hicks J K, et al. PubMed
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Pharmacogenetic determinants of mercaptopurine disposition in children with acute lymphoblastic leukemia. European journal of clinical pharmacology. 2012. Adam de Beaumais Tiphaine, et al. PubMed
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PACSIN2 polymorphism influences TPMT activity and mercaptopurine-related gastrointestinal toxicity. Human molecular genetics. 2012. Stocco Gabriele, et al. PubMed
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Genetic variants of thiopurine and folate metabolic pathways determine 6-MP-mediated hematological toxicity in childhood ALL. Pharmacogenomics. 2012. Dorababu Patchva, et al. PubMed
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6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner. Pharmacogenomics. 2012. Kotur Nikola, et al. PubMed
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Pharmacogenetic analysis of pediatric patients with acute lymphoblastic leukemia: a possible association between survival rate and ITPA polymorphism. PloS one. 2012. Kim Hyery, et al. PubMed
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Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients. Alimentary pharmacology & therapeutics. 2011. González-Lama Y, et al. PubMed
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A pharmacogenetics study of TPMT and ITPA genes detects a relationship with side effects and clinical response in patients with inflammatory bowel disease receiving Azathioprine. Journal of gastrointestinal and liver diseases : JGLD. 2011. Zabala-Fernández William, et al. PubMed
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Thiopurine S-methyltransferase polymorphism in Iranian kidney transplant recipients. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2011. Aghdaie Mahdokht Hossein, et al. PubMed
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Azathioprine-related myelosuppression in a patient homozygous for TPMT*3A. Nature reviews. Nephrology. 2011. Budhiraja Pooja, et al. PubMed
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Cancer Pharmacogenomics. Clinical pharmacology and therapeutics. 2011. Paugh S W, et al. PubMed
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Pharmacogenomics of cisplatin-induced ototoxicity. Pharmacogenomics. 2011. Mukherjea Debashree, et al. PubMed
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Prospective-retrospective biomarker analysis for regulatory consideration: white paper from the industry pharmacogenomics working group. Pharmacogenomics. 2011. Patterson Scott D, et al. PubMed
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Nodular regenerative liver hyperplasia as a complication of azathioprine-containing immunosuppressive treatment for Crohn's disease. Immunopharmacology and immunotoxicology. 2011. Błogowski Wojciech, et al. PubMed
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A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study. Pharmacogenomics. 2011. Newman William G, et al. PubMed
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Pharmacogenetics and individualized therapy in children: immunosuppressants, antidepressants, anticancer and anti-inflammatory drugs. Pharmacogenomics. 2011. Elie Valery, et al. PubMed
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Pediatric pharmacogenetic and pharmacogenomic studies: the current state and future perspectives. European journal of clinical pharmacology. 2011. Russo Roberta, et al. PubMed
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Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy. British journal of clinical pharmacology. 2011. Adam de Beaumais Tiphaine, et al. PubMed
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Economic impact of a genetic test for cisplatin-induced ototoxicity. The pharmacogenomics journal. 2011. Dionne F, et al. PubMed
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Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clinical pharmacology and therapeutics. 2011. Relling M V, et al. PubMed
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Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
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Regulation of phase II biotransformation enzymes by steroid hormones. Current drug metabolism. 2011. Kohalmy Krisztina, et al. PubMed
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Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al. PubMed
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Pharmacogenomic contribution to drug response. Cancer journal (Sudbury, Mass.). 2011. Watson Roshawn G, et al. PubMed
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Ecto-5'-nucleotidase and thiopurine cellular circulation: association with cytotoxicity. Drug metabolism and disposition: the biological fate of chemicals. 2010. Li Fang, et al. PubMed
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Thiopurine methyltransferase predicts the extent of cytotoxicty and DNA damage in astroglial cells after thioguanine exposure. PloS one. 2011. Hosni-Ahmed Amira, et al. PubMed
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Identifying genomic and developmental causes of adverse drug reactions in children. Pharmacogenomics. 2010. Becker Mara L, et al. PubMed
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Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
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Characterization of 107 genomic DNA reference materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1: a GeT-RM and Association for Molecular Pathology collaborative project. The Journal of molecular diagnostics : JMD. 2010. Pratt Victoria M, et al. PubMed
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Genetic analysis of thiopurine methyltransferase polymorphism in the Jordanian population. European journal of clinical pharmacology. 2010. Hakooz Nancy, et al. PubMed
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The multidrug-resistance protein 4 polymorphism is a new factor accounting for thiopurine sensitivity in Japanese patients with inflammatory bowel disease. Journal of gastroenterology. 2010. Ban Hiromistu, et al. PubMed
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Thiopurine pathway. Pharmacogenetics and genomics. 2010. Zaza Gianluigi, et al. PubMed
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Thiopurine S-methyltransferase gene polymorphism and 6-mercaptopurine dose intensity in Indian children with acute lymphoblastic leukemia. Leukemia research. 2010. Kapoor Gauri, et al. PubMed
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Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease. World journal of gastroenterology : WJG. 2010. Dong Xian-Wen, et al. PubMed
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Very important pharmacogene summary: thiopurine S-methyltransferase. Pharmacogenetics and genomics. 2010. Wang Liewei, et al. PubMed
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Clinical implementation of pharmacogenomics: overcoming genetic exceptionalism. The lancet oncology. 2010. Relling Mary V, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: functional characterization of a novel rapidly degraded variant allozyme. Biochemical pharmacology. 2010. Feng Qiping, et al. PubMed
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Thiopurine S-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come. Journal of clinical pathology. 2010. Ford L T, et al. PubMed
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Functional analysis of the role of the TPMT gene promoter VNTR polymorphism in TPMT gene transcription. Pharmacogenomics. 2010. Zukic Branka, et al. PubMed
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Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2010. Ansari A, et al. PubMed
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Frequency of thiopurine S-methyltransferase (TPMT) alleles in southeast Iranian population. Nucleosides, nucleotides & nucleic acids. 2010. Bahari Ali, et al. PubMed
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Pharmacogenomics in the treatment of inflammatory bowel disease. Pharmacogenomics. 2010. Smith Melissa A, et al. PubMed
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Thiopurine S-methyltransferase genotype and the use of thiopurines in paediatric inflammatory bowel disease Greek patients. Journal of clinical pharmacy and therapeutics. 2010. Gazouli M, et al. PubMed
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Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia. Leukemia. 2010. Schmiegelow K, et al. PubMed
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Are patients with intermediate TPMT activity at increased risk of myelosuppression when taking thiopurine medications?. Pharmacogenomics. 2010. Higgs Jenny E, et al. PubMed
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SNPs in genes coding for ROS metabolism and signalling in association with docetaxel clearance. The pharmacogenomics journal. 2010. Edvardsen H, et al. PubMed
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Influences of thiopurine methyltransferase genotype and activity on thiopurine-induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study. Journal of clinical gastroenterology. 2010. Kim Jae Hak, et al. PubMed
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Thiopurine S-methyltransferase (TPMT) genetic polymorphisms in Mexican newborns. Journal of clinical pharmacy and therapeutics. 2009. González-Del Angel A, et al. PubMed
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Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy. Nature genetics. 2009. Ross Colin J D, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics in a large-scale healthy Italian-Caucasian population: differences in enzyme activity. Pharmacogenomics. 2009. Serpe Loredana, et al. PubMed
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Variation in care in pediatric Crohn disease. Journal of pediatric gastroenterology and nutrition. 2009. Colletti Richard B, et al. PubMed
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Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2009. Smith M A, et al. PubMed
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Thiopurine methyltransferase genetics is not a major risk factor for secondary malignant neoplasms after treatment of childhood acute lymphoblastic leukemia on Berlin-Frankfurt-Münster protocols. Blood. 2009. Stanulla Martin, et al. PubMed
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Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain. European journal of human genetics : EJHG. 2009. Gurwitz David, et al. PubMed
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Clinically available pharmacogenomics tests. Clinical pharmacology and therapeutics. 2009. Flockhart D A, et al. PubMed
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Impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand. Clinical therapeutics. 2009. Vannaprasaht Suda, et al. PubMed
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Adverse reactions to azathioprine cannot be predicted by thiopurine S-methyltransferase genotype in Japanese patients with inflammatory bowel disease. Journal of gastroenterology and hepatology. 2009. Takatsu Noritaka, et al. PubMed
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Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study. Blood. 2009. Schmiegelow Kjeld, et al. PubMed
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ADME pharmacogenetics: current practices and future outlook. Expert opinion on drug metabolism & toxicology. 2009. Grossman Iris. PubMed
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Heterozygosity at the TPMT gene locus, augmented by mutated MTHFR gene, predisposes to 6-MP related toxicities in childhood ALL patients. Leukemia. 2009. Karas-Kuzelicki N, et al. PubMed
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Application of SNaPshot for analysis of thiopurine methyltransferase gene polymorphism. The Indian journal of medical research. 2009. Kapoor Gauri, et al. PubMed
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Distribution of TPMT risk alleles for thiopurine [correction of thioupurine] toxicity in the Israeli population. European journal of clinical pharmacology. 2009. Efrati Edna, et al. PubMed
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Relationships between thiopurine S-methyltransferase polymorphism and azathioprine-related adverse drug reactions in Chinese renal transplant recipients. European journal of clinical pharmacology. 2009. Xin Hua-Wen, et al. PubMed
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Thiopurine methyltransferase activity is related to the risk of relapse of childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2009. Schmiegelow K, et al. PubMed
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Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. Clinical pharmacology and therapeutics. 2009. Stocco G, et al. PubMed
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TPMT genetic variations in populations of the Russian Federation. Pediatric blood & cancer. 2009. Samochatova Elena V, et al. PubMed
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Pharmacogenetics and pharmacogenomics of anticancer agents. CA: a cancer journal for clinicians. 2009. Huang R Stephanie, et al. PubMed
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Duplex pyrosequencing of the TPMT*3C and TPMT*6 alleles in Korean and Vietnamese populations. Clinica chimica acta; international journal of clinical chemistry. 2008. Lee Sang Seop, et al. PubMed
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Thiopurine methyltransferase gene polymorphisms in Chinese patients with inflammatory bowel disease. Digestion. 2009. Cao Qian, et al. PubMed
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Allele frequency of thiopurine methyltransferase and inosine triphosphate pyrophosphatase gene polymorphisms in Korean patients with inflammatory bowel diseases. Hepato-gastroenterology. 2009. Cheon Jae Hee, et al. PubMed
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Importance of thiopurine S-Methyltransferase gene polymorphisms for prediction of azathioprine toxicity. Neuro endocrinology letters. 2009. Kolorz Michal, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: autophagy as a mechanism for variant allozyme degradation. Pharmacogenetics and genomics. 2008. Li Fang, et al. PubMed
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Thiopurine S-methyltransferase (TPMT) gene polymorphism in Brazilian children with acute lymphoblastic leukemia: association with clinical and laboratory data. Therapeutic drug monitoring. 2008. Silva Marcilene Rezende, et al. PubMed
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Prospective evaluation of the pharmacogenetics of azathioprine in the treatment of inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2008. Ansari A, et al. PubMed
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Highly multiplexed genotyping of thiopurine s-methyltransferase variants using MALD-TOF mass spectrometry: reliable genotyping in different ethnic groups. Clinical chemistry. 2008. Schaeffeler Elke, et al. PubMed
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Pharmacogenomics: candidate gene identification, functional validation and mechanisms. Human molecular genetics. 2008. Wang Liewei, et al. PubMed
Functional characterization of 23 allelic variants of thiopurine S-methyltransferase gene (TPMT*2 - *24). Pharmacogenetics and genomics. 2008. Ujiie Shuta, et al. PubMed
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Long-term outcome of using allopurinol co-therapy as a strategy for overcoming thiopurine hepatotoxicity in treating inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2008. Ansari A, et al. PubMed
Characterisation of novel defective thiopurine S-methyltransferase allelic variants. Biochemical pharmacology. 2008. Garat A, et al. PubMed
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Pathway based analysis of SNPs with relevance to 5-FU therapy: relation to intratumoral mRNA expression and survival. International journal of cancer. Journal international du cancer. 2008. Nordgard Silje H, et al. PubMed
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Creating and evaluating genetic tests predictive of drug response. Nature reviews. Drug discovery. 2008. Weiss Scott T, et al. PubMed
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Structural basis of substrate recognition in thiopurine s-methyltransferase. Biochemistry. 2008. Peng Yi, et al. PubMed
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Thiopurine dose in intermediate and normal metabolizers of thiopurine methyltransferase may differ three-fold. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2008. Gardiner Sharon J, et al. PubMed
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Polymorphisms of the TPMT gene in the Czech healthy population and patients with inflammatory bowel disease. Nucleosides, nucleotides & nucleic acids. 2008. Slanar Ondrej, et al. PubMed
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Trinucleotide repeat variants in the promoter of the thiopurine S-methyltransferase gene of patients exhibiting ultra-high enzyme activity. Pharmacogenetics and genomics. 2008. Roberts Rebecca L, et al. PubMed
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Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency. American journal of hematology. 2008. Yenson Paul R, et al. PubMed
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Thiopurine-methyltransferase and inosine triphosphate pyrophosphatase polymorphism in a liver transplant recipient developing nodular regenerative hyperplasia on low-dose azathioprine. European journal of gastroenterology & hepatology. 2008. Buster Erik H C J, et al. PubMed
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Thiopurine S-methyltransferase (TPMT) pharmacogenetics: three new mutations and haplotype analysis in the Estonian population. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2008. Tamm Riin, et al. PubMed
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Analysis of thiopurine S-methyltransferase genotypes in Japanese patients with inflammatory bowel disease. Internal medicine (Tokyo, Japan). 2008. Ban Hiromitsu, et al. PubMed
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Thiopurine S-methyltransferase gene (TMPT) polymorphisms in a Mexican population of healthy individuals and leukemic patients. Medical oncology (Northwood, London, England). 2008. Taja-Chayeb Lucia, et al. PubMed
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Pharmacogenomics of drug-metabolizing enzymes and drug transporters in chemotherapy. Methods in molecular biology (Clifton, N.J.). 2008. Bosch Tessa M. PubMed
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Pharmacoeconomic evaluations of pharmacogenetic and genomic screening programmes: a systematic review on content and adherence to guidelines. PharmacoEconomics. 2008. Vegter Stefan, et al. PubMed
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The low frequency of defective TPMT alleles in Turkish population: a study on pediatric patients with acute lymphoblastic leukemia. American journal of hematology. 2007. Tumer Tugba Boyunegmez, et al. PubMed
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Genetic polymorphisms of folate metabolic enzymes and toxicities of high dose methotrexate in children with acute lymphoblastic leukemia. Annals of hematology. 2007. Pakakasama Samart, et al. PubMed
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Do the distribution patterns of polymorphisms at the thiopurine S-methyltransferase locus in sub-Saharan populations need revision? Hints from Cabinda and Mozambique. European journal of clinical pharmacology. 2007. Oliveira E, et al. PubMed
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Assessment of thiopurine methyltransferase enzyme activity is superior to genotype in predicting myelosuppression following azathioprine therapy in patients with inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2007. Winter J W, et al. PubMed
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Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood. 2007. Kishi Shinji, et al. PubMed
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Differential effects of targeted disruption of thiopurine methyltransferase on mercaptopurine and thioguanine pharmacodynamics. Cancer research. 2007. Hartford Christine, et al. PubMed
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Using HapMap tools in pharmacogenomic discovery: the thiopurine methyltransferase polymorphism. Clinical pharmacology and therapeutics. 2007. Jones T S, et al. PubMed
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Current use of pharmacogenetic testing: a national survey of thiopurine methyltransferase testing prior to azathioprine prescription. Journal of clinical pharmacy and therapeutics. 2007. Fargher E A, et al. PubMed
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Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China). Clinica chimica acta; international journal of clinical chemistry. 2007. Zhang Li-Rong, et al. PubMed
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Thiopurine S-methyltransferase gene polymorphism in Japanese patients with autoimmune liver diseases. Liver international : official journal of the International Association for the Study of the Liver. 2007. Tamori Akihiro, et al. PubMed
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Monitoring of thiopurine methyltransferase activity in postsurgical patients with Crohn's disease during 1 year of treatment with azathioprine or mesalazine. Therapeutic drug monitoring. 2007. Dilger Karin, et al. PubMed
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Genetic analyses of thiopurine methyltransferase polymorphisms in Greenlandic and Danish populations. Acta paediatrica (Oslo, Norway : 1992). 2006. Toft Nina, et al. PubMed
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TPMT genotype and its clinical implication in renal transplant recipients with azathioprine treatment. Journal of clinical pharmacy and therapeutics. 2006. Song D-K, et al. PubMed
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Overview of the pharmacoeconomics of pharmacogenetics. Pharmacogenomics. 2006. Dervieux Thierry, et al. PubMed
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Analysis of thiopurine S-methyltransferase polymorphism in the population of Serbia and Montenegro and mercaptopurine therapy tolerance in childhood acute lymphoblastic leukemia. Therapeutic drug monitoring. 2006. Dokmanovic Lidija, et al. PubMed
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The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clinical pharmacology and therapeutics. 2006. Lennard Lynne, et al. PubMed
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Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut. 2006. Hindorf U, et al. PubMed
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Three novel thiopurine S-methyltransferase allelic variants (TPMT*20, *21, *22) - association with decreased enzyme function. Human mutation. 2006. Schaeffeler Elke, et al. PubMed
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The frequency and significance of thiopurine S-methyltransferase gene polymorphisms in azathioprine-treated renal transplant recipients. The British journal of dermatology. 2006. Moloney F J, et al. PubMed
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Pharmacogenetics of thiopurine therapy in paediatric IBD patients. Alimentary pharmacology & therapeutics. 2006. De Ridder L, et al. PubMed
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Determination of intra-ethnic differences in the polymorphisms of thiopurine S-methyltransferase in Chinese. Clinica chimica acta; international journal of clinical chemistry. 2006. Zhang Jian-Ping, et al. PubMed
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Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial. Lancet. 2006. Meggitt Simon J, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: insights, challenges and future directions. Oncogene. 2006. Wang L, et al. PubMed
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Molecular analysis of thiopurine S-methyltransferase alleles in Taiwan aborigines and Taiwanese. Journal of clinical pharmacy and therapeutics. 2006. Lu H-F, et al. PubMed
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Thiopurine methyltransferase in acute lymphoblastic leukemia. Blood. 2006. Relling Mary V, et al. PubMed
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Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2006. Zelinkova Zuzana, et al. PubMed
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Pharmacogenomics and individualized drug therapy. Annual review of medicine. 2006. Eichelbaum Michel, et al. PubMed
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Pharmacogenomics: catechol O-methyltransferase to thiopurine S-methyltransferase. Cellular and molecular neurobiology. 2006. Weinshilboum Richard M. PubMed
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TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2005. Stocco G, et al. PubMed
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Thiopurine S-methyltransferase phenotype-genotype correlation in hemodialyzed patients. Pharmacological reports : PR. 2006. Chrzanowska Maria, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: genotype to phenotype correlation in the Slovenian population. Pharmacology. 2006. Milek M, et al. PubMed
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Thiopurine methyltransferase genotype and phenotype status in Japanese patients with systemic lupus erythematosus. Biological & pharmaceutical bulletin. 2005. Okada Yuko, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: variant allele functional and comparative genomics. Pharmacogenetics and genomics. 2005. Salavaggione Oreste E, et al. PubMed
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Thiopurine methyltransferase and 6-thioguanine nucleotide measurement: early experience of use in clinical practice. Internal medicine journal. 2005. Gearry R B, et al. PubMed
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Molecular analysis of the thiopurine S-methyltransferase alleles in Bolivians and Tibetans. Journal of clinical pharmacy and therapeutics. 2005. Lu H-F, et al. PubMed
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Phenotyping and genotyping studies of thiopurine S-methyltransferase in Kazaks. Pharmaceutical research. 2005. Wei Hong, et al. PubMed
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A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. The American journal of gastroenterology. 2005. Dubinsky Marla C, et al. PubMed
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Karyotypic abnormalities create discordance of germline genotype and cancer cell phenotypes. Nature genetics. 2005. Cheng Qing, et al. PubMed
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The impact of thiopurine s-methyltransferase polymorphism on azathioprine-induced myelotoxicity in renal transplant recipients. Therapeutic drug monitoring. 2005. Kurzawski Mateusz, et al. PubMed
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Pharmacogenetic association with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2005. Breen David P, et al. PubMed
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Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood. 2005. Rocha Jose Claudio C, et al. PubMed
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Human thiopurine S-methyltransferase pharmacogenetics: variant allozyme misfolding and aggresome formation. Proceedings of the National Academy of Sciences of the United States of America. 2005. Wang Liewei, et al. PubMed
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Thiopurine methyltransferase (TPMT) heterozygosity and enzyme activity as predictive tests for the development of azathioprine-related adverse events. Journal of the neurological sciences. 2005. Heckmann Jeannine M, et al. PubMed
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Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA : the journal of the American Medical Association. 2005. Stanulla Martin, et al. PubMed
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Identification and functional analysis of two rare allelic variants of the thiopurine S-methyltransferase gene, TPMT*16 and TPMT*19. Biochemical pharmacology. 2005. Hamdan-Khalil Rima, et al. PubMed
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Lymphoid gene expression as a predictor of risk of secondary brain tumors. Genes, chromosomes & cancer. 2005. Edick Mathew J, et al. PubMed
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Thiopurine S-methyltransferase polymorphisms and the relationship between the mutant alleles and the adverse effects in systemic lupus erythematosus patients taking azathioprine. Clinical and experimental rheumatology. 2005. Jun J B, et al. PubMed
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Guidelines for prescribing azathioprine in dermatology. The British journal of dermatology. 2004. Anstey A V, et al. PubMed
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Thiopurine S-methyltransferase genotype predicts azathioprine-induced myelotoxicity in kidney transplant recipients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2004. Formea Christine M, et al. PubMed
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Monitoring of long-term thiopurine therapy among adults with inflammatory bowel disease. Scandinavian journal of gastroenterology. 2004. Hindorf U, et al. PubMed
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Frequency distribution of thiopurine S-methyltransferase alleles in a polish population. Therapeutic drug monitoring. 2004. Kurzawski Mateusz, et al. PubMed
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The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation. Transplant international : official journal of the European Society for Organ Transplantation. 2004. Fabre Margarete A, et al. PubMed
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Rapid, long-range molecular haplotyping of thiopurine S-methyltransferase (TPMT) *3A, *3B, and *3C. Clinical chemistry. 2004. von Ahsen Nicolas, et al. PubMed
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Tracing the origin of the most common thiopurine methyltransferase (TPMT) variants: preliminary data from the patterns of haplotypic association with two CA repeats. Annals of human genetics. 2004. Alves S, et al. PubMed
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Thiopurine S-methyltransferase genetic polymorphism in the Thai population. British journal of clinical pharmacology. 2004. Srimartpirom Somrudee, et al. PubMed
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RT-PCR permits simultaneous genotyping of thiopurine S-methyltransferase allelic variants by multiplex induced heteroduplex analysis. Human mutation. 2004. Wood Nigel, et al. PubMed
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Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics. 2004. Schaeffeler Elke, et al. PubMed
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Methylated metabolites of 6-mercaptopurine are associated with hepatotoxicity. Clinical pharmacology and therapeutics. 2004. Nygaard Ulrikka, et al. PubMed
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Phenotype and genotype for thiopurine methyltransferase activity in the French Caucasian population: impact of age. European journal of clinical pharmacology. 2004. Ganiere-Monteil Catherine, et al. PubMed
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Analysis of variation in mouse TPMT genotype, expression and activity. Pharmacogenetics. 2004. Watters James W, et al. PubMed
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Identification of two novel sequence variants affecting thiopurine methyltransferase enzyme activity. Pharmacogenetics. 2004. Lindqvist Malin, et al. PubMed
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Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy. Therapeutic drug monitoring. 2004. Evans William E. PubMed
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Thiopurine S-methyltransferase polymorphisms: efficient screening method for patients considering taking thiopurine drugs. European journal of clinical pharmacology. 2004. Wusk Barbara, et al. PubMed
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Pyrosequencing of TPMT alleles in a general Swedish population and in patients with inflammatory bowel disease. Clinical chemistry. 2004. Haglund Sofie, et al. PubMed
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Pharmacogenomics and IBD: TPMT and thiopurines. Inflammatory bowel diseases. 2004. Sandborn William J. PubMed
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Mistaken identity: misclassification of TPMT phenotype following blood transfusion. European journal of gastroenterology & hepatology. 2003. Cheung Seau-Tak, et al. PubMed
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In vitro characterization of four novel non-functional variants of the thiopurine S-methyltransferase. Biochemical and biophysical research communications. 2003. Hamdan-Khalil Rima, et al. PubMed
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Drug methylation in cancer therapy: lessons from the TPMT polymorphism. Oncogene. 2003. Krynetski Eugene, et al. PubMed
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Phenotypic and genotypic analysis of thiopurine s-methyltransferase polymorphism in the bulgarian population. Therapeutic drug monitoring. 2003. Indjova Dessislava, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: chaperone protein association and allozyme degradation. Pharmacogenetics. 2003. Wang Liewei, et al. PubMed
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Genetic polymorphism of thiopurine S-methyltransferase in Argentina. Annals of clinical biochemistry. 2003. Laróvere L E, et al. PubMed
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Dose reduction of coadministered 6-mercaptopurine decreases myelotoxicity following high-dose methotrexate in childhood leukemia. Leukemia. 2003. Nygaard U, et al. PubMed
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Genotype and allele frequencies of TPMT, NAT2, GST, SULT1A1 and MDR-1 in the Egyptian population. British journal of clinical pharmacology. 2003. Hamdy Samar I, et al. PubMed
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Thiopurine methyltransferase phenotypes and genotypes in Brazilians. Pharmacogenetics. 2003. Reis Marcelo, et al. PubMed
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[Genetic polymorphism of the thiopurine S-methyltransferase of healthy Han Chinese]. Ai zheng = Aizheng = Chinese journal of cancer. 2003. Zhang Jian-Ping, et al. PubMed
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Genetic determinants of the thiopurine methyltransferase intermediate activity phenotype in British Asians and Caucasians. Pharmacogenetics. 2003. Marinaki Anthony M, et al. PubMed
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Inheritance and drug response. The New England journal of medicine. 2003. Weinshilboum Richard. PubMed
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Thiopurine methyltransferase genotype distribution in patients with Crohn's disease. Alimentary pharmacology & therapeutics. 2003. Reuther L O, et al. PubMed
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Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine. Gut. 2003. Kaskas B A, et al. PubMed
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Is thiopurine methyltransferase genetic polymorphism a major factor for withdrawal of azathioprine in rheumatoid arthritis patients?. Rheumatology (Oxford, England). 2003. Corominas H, et al. PubMed
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Allelic variants of the thiopurine methyltransferase (TPMT) gene in the Colombian population. Methods and findings in experimental and clinical pharmacology. 2003. Isaza C, et al. PubMed
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Practical pharmacogenetics: the cost effectiveness of screening for thiopurine s-methyltransferase polymorphisms in patients with rheumatological conditions treated with azathioprine. The Journal of rheumatology. 2002. Marra Carlo A, et al. PubMed
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Thiopurine methyltransferase polymorphisms in a Brazilian population. The pharmacogenomics journal. 2003. Boson W L, et al. PubMed
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Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2002. Ansari A, et al. PubMed
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Cefazolin administration and 2-methyl-1,3,4-thiadiazole-5-thiol in human tissue: possible relationship to hypoprothrombinemia. Drug metabolism and disposition: the biological fate of chemicals. 2002. Wood Thomas C, et al. PubMed
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Determination of thiopurine methyltransferase genotype or phenotype optimizes initial dosing of azathioprine for the treatment of Crohn's disease. Journal of clinical gastroenterology. 2002. Regueiro Miguel, et al. PubMed
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Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism. Pharmacogenetics. 2002. Schwab Matthias, et al. PubMed
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Molecular analysis of thiopurine S-methyltransferase alleles in South-east Asian populations. Pharmacogenetics. 2002. Chang Jan-Gowth, et al. PubMed
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Interaction between azathioprine and aminosalicylates: an in vivo study in patients with Crohn's disease. Alimentary pharmacology & therapeutics. 2002. Dewit O, et al. PubMed
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The thiopurine S-methyltransferase gene locus -- implications for clinical pharmacogenomics. Pharmacogenomics. 2002. McLeod Howard L, et al. PubMed
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Thiopurine methyltransferase polymorphisms in a multiracial asian population and children with acute lymphoblastic leukemia. Journal of pediatric hematology/oncology. 2002. Kham S K Y, et al. PubMed
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Human thiopurine methyltransferase activity varies with red blood cell age. British journal of clinical pharmacology. 2001. Lennard L, et al. PubMed
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Pitfalls in the determination of mutant alleles of the thiopurine methyltransferase gene. Leukemia. 2001. Brouwer C, et al. PubMed
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Differing contribution of thiopurine methyltransferase to mercaptopurine versus thioguanine effects in human leukemic cells. Cancer research. 2001. Dervieux T, et al. PubMed
Influence of the variable number of tandem repeats located in the promoter region of the thiopurine methyltransferase gene on enzymatic activity. Clinical pharmacology and therapeutics. 2001. Alves S, et al. PubMed
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Shortcoming in the diagnosis of TPMT deficiency in a patient with Crohn's disease using phenotyping only. Gastroenterology. 2001. Schwab M, et al. PubMed
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Frequencies of thiopurine S-methyltransferase mutant alleles (TPMT*2, *3A, *3B and *3C) in 151 healthy Japanese subjects and the inheritance of TPMT*3C in the family of a propositus. British journal of clinical pharmacology. 2001. Kubota T, et al. PubMed
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Rational dosing of azathioprine and 6-mercaptopurine. Gut. 2001. Sandborn W J. PubMed
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Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase. Drug metabolism and disposition: the biological fate of chemicals. 2001. Weinshilboum R. PubMed
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Genotype-phenotype correlation for thiopurine S-methyltransferase in healthy Italian subjects. European journal of clinical pharmacology. 2001. Rossi A M, et al. PubMed
Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001. Evans W E, et al. PubMed
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Allelotype frequency of the thiopurine methyltransferase (TPMT) gene in Japanese. Pharmacogenetics. 2001. Kumagai K, et al. PubMed
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Genetic polymorphisms of thiopurine S-methyltransferase and 6-mercaptopurine toxicity in Japanese children with acute lymphoblastic leukaemia. Pharmacogenetics. 2001. Ando M, et al. PubMed
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Therapeutic drug monitoring of cytotoxic drugs. British journal of clinical pharmacology. 2001. Lennard L. PubMed
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Genotyping of eight thiopurine methyltransferase mutations: three-color multiplexing, "two-color/shared" anchor, and fluorescence-quenching hybridization probe assays based on thermodynamic nearest-neighbor probe design. Clinical chemistry. 2000. Schütz E, et al. PubMed
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Thioguanine substitution alters DNA cleavage mediated by topoisomerase II. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000. Krynetskaia N F, et al. PubMed
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Frequency of thiopurine S-methyltransferase genetic variation in Thai children with acute leukemia. Medical and pediatric oncology. 2000. Hongeng S, et al. PubMed
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Allelic variants of the thiopurine S-methyltransferase deficiency in patients with ulcerative colitis and in healthy controls. The American journal of gastroenterology. 2000. Corominas H, et al. PubMed
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Thiopurine methyltransferase polymorphic tandem repeat: genotype-phenotype correlation analysis. Clinical pharmacology and therapeutics. 2000. Yan L, et al. PubMed
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Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000. Colombel J F, et al. PubMed
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Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology. 2000. Dubinsky M C, et al. PubMed
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Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000. McLeod H L, et al. PubMed
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Thiopurine S-methyltransferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients. Transplantation. 2000. Sebbag L, et al. PubMed
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Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population. Mutation research. 2000. Hiratsuka M, et al. PubMed
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Characterization of three new VNTR alleles in the promoter region of the TPMT gene. Human mutation. 2000. Alves S, et al. PubMed
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Severe 6-thioguanine-induced marrow aplasia in a child with acute lymphoblastic leukemia and inherited thiopurine methyltransferase deficiency. Journal of pediatric hematology/oncology. 2000. McBride K L, et al. PubMed
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Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. Journal of the National Cancer Institute. 1999. Relling M V, et al. PubMed
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Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals. Pharmacogenetics. 1999. McLeod H L, et al. PubMed
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Enhanced proteasomal degradation of mutant human thiopurine S-methyltransferase (TPMT) in mammalian cells: mechanism for TPMT protein deficiency inherited by TPMT*2, TPMT*3A, TPMT*3B or TPMT*3C. Pharmacogenetics. 1999. Tai H L, et al. PubMed
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Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells: relation to thiopurine metabolism. Cancer. 1999. Bo J, et al. PubMed
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High incidence of secondary brain tumours after radiotherapy and antimetabolites. Lancet. 1999. Relling M V, et al. PubMed
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Analysis of thiopurine methyltransferase variant alleles in childhood acute lymphoblastic leukaemia. British journal of haematology. 1999. McLeod H L, et al. PubMed
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Prognostic importance of 6-mercaptopurine dose intensity in acute lymphoblastic leukemia. Blood. 1999. Relling M V, et al. PubMed
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Characterization of a variable number tandem repeat region in the thiopurine S-methyltransferase gene promoter. Pharmacogenetics. 1999. Spire-Vayron de la Moureyre C, et al. PubMed
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Thiopurine methyltransferase pharmacogenetics: alternative molecular diagnosis and preliminary data from Northern Portugal. Pharmacogenetics. 1999. Alves S, et al. PubMed
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Therapeutic drug monitoring of antimetabolic cytotoxic drugs. British journal of clinical pharmacology. 1999. Lennard L. PubMed
Polymorphism of the thiopurine S-methyltransferase gene in African-Americans. Human molecular genetics. 1999. Hon Y Y, et al. PubMed
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Thiopurine methyltransferase alleles in British and Ghanaian populations. Human molecular genetics. 1999. Ameyaw M M, et al. PubMed
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The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. Pharmacogenetics. 1999. Collie-Duguid E S, et al. PubMed
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Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. Annals of internal medicine. 1998. Black A J, et al. PubMed
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Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population. British journal of pharmacology. 1998. Spire-Vayron de la Moureyre C, et al. PubMed
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Clinical implications of thiopurine methyltransferase--optimization of drug dosage and potential drug interactions. Therapeutic drug monitoring. 1998. Lennard L. PubMed
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Pharmacogenetics of cancer therapy: getting personal. American journal of human genetics. 1998. Krynetski E Y, et al. PubMed
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Etoposide and antimetabolite pharmacology in patients who develop secondary acute myeloid leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998. Relling M V, et al. PubMed
Human thiopurine methyltransferase pharmacogenetics. Kindred with a terminal exon splice junction mutation that results in loss of activity. The Journal of clinical investigation. 1998. Otterness D M, et al. PubMed
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Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency. Acta paediatrica (Oslo, Norway : 1992). 1998. Andersen J B, et al. PubMed
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Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. Clinical pharmacology and therapeutics. 1997. Otterness D, et al. PubMed
Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity. Proceedings of the National Academy of Sciences of the United States of America. 1997. Tai H L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Annals of internal medicine. 1997. Yates C R, 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
Individualizing therapy with 6-mercaptopurine and 6-thioguanine related to the thiopurine methyltransferase genetic polymorphism. Therapeutic drug monitoring. 1996. Lennard L, et al. PubMed
Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians. American journal of human genetics. 1996. Tai H L, et al. PubMed
Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism. DNA and cell biology. 1996. Szumlanski C, 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
Methylation of mercaptopurine, thioguanine, and their nucleotide metabolites by heterologously expressed human thiopurine S-methyltransferase. Molecular pharmacology. 1995. Krynetski E Y, 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
Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine. British journal of clinical pharmacology. 1995. Szumlanski C L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1. Drug metabolism and disposition: the biological fate of chemicals. 1995. Lee D, et al. PubMed
A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proceedings of the National Academy of Sciences of the United States of America. 1995. Krynetski E Y, 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
Purine substrates for human thiopurine methyltransferase. Biochemical pharmacology. 1994. Deininger 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
Decrease in S-adenosylmethionine synthesis by 6-mercaptopurine and methylmercaptopurine ribonucleoside in Molt F4 human malignant lymphoblasts. The Biochemical journal. 1994. Stet E H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia. Archives of disease in childhood. 1993. Lennard L, 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
Reversal of 6-mercaptopurine and 6-methylmercaptopurine ribonucleoside cytotoxicity by amidoimidazole carboxamide ribonucleoside in Molt F4 human malignant T-lymphoblasts. Biochemical pharmacology. 1993. Stet E H, 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
Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet. 1993. McLeod H L, 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
6-Mercaptopurine: cytotoxicity and biochemical pharmacology in human malignant T-lymphoblasts. Biochemical pharmacology. 1993. Bökkerink J P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Human liver thiopurine methyltransferase pharmacogenetics: biochemical properties, liver-erythrocyte correlation and presence of isozymes. Pharmacogenetics. 1992. Szumlanski C L, et al. PubMed
Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemia. The Journal of pediatrics. 1991. Evans W E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet. 1990. Lennard L, 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
Thiopurine methyltransferase isozymes in human renal tissue. Drug metabolism and disposition: the biological fate of chemicals. 1990. Van Loon J A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clinical pharmacology and therapeutics. 1989. Lennard L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Thiopurine pharmacogenetics in leukemia: correlation of erythrocyte thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations. Clinical pharmacology and therapeutics. 1987. Lennard L, 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 effects of 6-mercaptopurine nucleotide derivatives on the growth and survival of 6-mercaptopurine-sensitive and -resistant cell culture lines. British journal of cancer. 1985. Johnston H P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Human kidney thiopurine methyltransferase. Purification and biochemical properties. Biochemical pharmacology. 1983. Woodson L C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Thiopurine methyltransferase biochemical genetics: human lymphocyte activity. Biochemical genetics. 1982. Van Loon J A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. American journal of human genetics. 1980. Weinshilboum R M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
6-Methylthioguanylic acid, a metabolite of 6-thioguanine. Biochemical pharmacology. 1971. Allan P W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Metabolism of thiopyrimidines and thiopurines. S-Methylation with S-adenosylmethionine transmethylase and catabolism in mammalian tissues. The Journal of biological chemistry. 1963. REMY C N. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ftp://ftpguest:4guest@ftp.pharmgkb.org/download/PKB_N00000021.pdf. [URL:ftp://ftpguest:4guest@ftp.pharmgkb.org/download/PKB_N00000021.pdf]

LinkOuts

Entrez Gene:
7172
OMIM:
187680
610460
UCSC Genome Browser:
NM_000367
RefSeq RNA:
NM_000367
RefSeq Protein:
NP_000358
RefSeq DNA:
AC_000049
AC_000138
NC_000006
NG_012137
NT_007592
NW_001838973
NW_922984
UniProtKB:
TPMT_HUMAN (P51580)
Q9BS45_HUMAN (Q9BS45)
Ensembl:
ENSG00000137364
GenAtlas:
TPMT
GeneCard:
TPMT
MutDB:
TPMT
ALFRED:
LO206732U
HuGE:
TPMT
Comparative Toxicogenomics Database:
7172
ModBase:
O43213
HumanCyc Gene:
HS06327
HGNC:
12014

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