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Aliases for TPMT Gene

Aliases for TPMT Gene

  • Thiopurine S-Methyltransferase 2 3 5
  • EC 4 63
  • S-Adenosyl-L-Methionine:Thiopurine S-Methyltransferase 3
  • Thiopurine Methyltransferase 4
  • TPMTD 3

External Ids for TPMT Gene

Previous GeneCards Identifiers for TPMT Gene

  • GC06M018186
  • GC06M018236

Summaries for TPMT Gene

Entrez Gene Summary for TPMT Gene

  • This gene encodes the enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents. Genetic polymorphisms that affect this enzymatic activity are correlated with variations in sensitivity and toxicity to such drugs within individuals, causing thiopurine S-methyltransferase deficiency. Related pseudogenes have been identified on chromosomes 3, 18 and X. [provided by RefSeq, Aug 2014]

GeneCards Summary for TPMT Gene

TPMT (Thiopurine S-Methyltransferase) is a Protein Coding gene. Diseases associated with TPMT include 6-Mercaptopurine Sensitivity and Tpmt-Related Altered Drug Metabolism. Among its related pathways are Phase II conjugation and One carbon pool by folate. GO annotations related to this gene include S-adenosylmethionine-dependent methyltransferase activity and thiopurine S-methyltransferase activity.

UniProtKB/Swiss-Prot for TPMT Gene

  • Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.

Gene Wiki entry for TPMT Gene

PharmGKB "VIP" Summary for TPMT Gene

No data available for Tocris Summary , fRNAdb sequence ontologies and piRNA Summary for TPMT Gene

Genomics for TPMT Gene

Regulatory Elements for TPMT Gene

Enhancers for TPMT Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around TPMT on UCSC Golden Path with GeneCards custom track

Promoters for TPMT Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around TPMT on UCSC Golden Path with GeneCards custom track

Genomic Location for TPMT Gene

18,128,311 bp from pter
18,155,165 bp from pter
26,855 bases
Minus strand

Genomic View for TPMT Gene

Genes around TPMT on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TPMT Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TPMT Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TPMT Gene

Proteins for TPMT Gene

  • Protein details for TPMT Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Thiopurine S-methyltransferase
    Protein Accession:
    Secondary Accessions:
    • O14806
    • O15423
    • O15424
    • O15425
    • O15426
    • O15515
    • O15548
    • O43213
    • Q5VUK6
    • Q9UBE6
    • Q9UBT8
    • Q9UE62

    Protein attributes for TPMT Gene

    245 amino acids
    Molecular mass:
    28180 Da
    Quaternary structure:
    • Monomer.
    • TPMT deficiency inherited by TPMT*2 and TPMT*3A alleles, are the most prevalent mutant TPMT in humans. TPMT deficiency is associated with lower cellular levels of TPMT protein, and the proteins encoded by TPMT*2 and TPMT*3A mutant alleles are degraded more rapidly by an ATP-dependent proteasome-mediated pathway.
    • Sequence=AAB71631.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAB71632.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TPMT Gene

neXtProt entry for TPMT Gene

Proteomics data for TPMT Gene at MOPED

Post-translational modifications for TPMT Gene

  • Ubiquitination at Lys 37
  • Modification sites at PhosphoSitePlus

Other Protein References for TPMT Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for TPMT Gene

Protein Domains for TPMT Gene

Suggested Antigen Peptide Sequences for TPMT Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.
  • Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.
genes like me logo Genes that share domains with TPMT: view

No data available for Gene Families for TPMT Gene

Function for TPMT Gene

Molecular function for TPMT Gene

GENATLAS Biochemistry:
thiopurine methyltransferase,cytosolic,catalyzing the S-methylation of thiopurine drugs
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=5.6 mM for S-adenosyl-L-methionine {ECO:0000269 PubMed:18484748}; KM=0.35 mM for 6-mercaptopurine {ECO:0000269 PubMed:18484748}; Vmax=0.6 nmol/sec/mg enzyme toward 6-mercaptopurine (at 37 degrees Celsius) {ECO:0000269 PubMed:18484748};
UniProtKB/Swiss-Prot CatalyticActivity:
S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by S-adenosyl-L-homocysteine (SAH).
UniProtKB/Swiss-Prot Function:
Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.

Enzyme Numbers (IUBMB) for TPMT Gene

genes like me logo Genes that share phenotypes with TPMT: view

Human Phenotype Ontology for TPMT Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TPMT Gene

MGI Knock Outs for TPMT:

Animal Model Products

  • Taconic Biosciences Mouse Models for TPMT

No data available for Gene Ontology (GO) - Molecular Function , Transcription Factor Targets and HOMER Transcription for TPMT Gene

Localization for TPMT Gene

Subcellular locations from UniProtKB/Swiss-Prot for TPMT Gene


Subcellular locations from

Jensen Localization Image for TPMT Gene COMPARTMENTS Subcellular localization image for TPMT gene
Compartment Confidence
cytosol 5
extracellular 5
nucleus 2
peroxisome 1

No data available for Gene Ontology (GO) - Cellular Components for TPMT Gene

Pathways & Interactions for TPMT Gene

genes like me logo Genes that share pathways with TPMT: view

Pathways by source for TPMT Gene

1 BioSystems pathway for TPMT Gene
1 KEGG pathway for TPMT Gene

Interacting Proteins for TPMT Gene

Gene Ontology (GO) - Biological Process for TPMT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0032259 methylation TAS --
genes like me logo Genes that share ontologies with TPMT: view

No data available for SIGNOR curated interactions for TPMT Gene

Drugs & Compounds for TPMT Gene

(49) Drugs for TPMT Gene - From: DrugBank, PharmGKB, ClinicalTrials, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Azathioprine Approved Pharma Enzyme, substrate 155
Mercaptopurine Approved Pharma Enzyme, substrate 0
Bendroflumethiazide Approved Pharma Enzyme, inhibitor 5
Cefazolin Approved Pharma Enzyme, substrate 104
Olsalazine Approved Pharma Target, inhibitor 1

(26) Additional Compounds for TPMT Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
6-Methylthioguanosine monophosphate
6-Methylthiopurine 5'-monophosphate ribonucleotide
6-Thioguanosine monophosphate
genes like me logo Genes that share compounds with TPMT: view

Transcripts for TPMT Gene

mRNA/cDNA for TPMT Gene

Unigene Clusters for TPMT Gene

Thiopurine S-methyltransferase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TPMT Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b · 10c
SP1: - -
SP2: -
SP3: - - -
SP4: -
SP6: -
SP7: - -

Relevant External Links for TPMT Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for TPMT Gene

mRNA expression in normal human tissues for TPMT Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TPMT Gene

This gene is overexpressed in Heart (11.3) and Liver (8.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for TPMT Gene

SOURCE GeneReport for Unigene cluster for TPMT Gene Hs.444319

genes like me logo Genes that share expression patterns with TPMT: view

Protein tissue co-expression partners for TPMT Gene

- Elite partner

Primer Products

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for TPMT Gene

Orthologs for TPMT Gene

This gene was present in the common ancestor of chordates.

Orthologs for TPMT Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia TPMT 35
  • 84.08 (n)
  • 77.14 (a)
  • 74 (a)
(Canis familiaris)
Mammalia TPMT 35
  • 84.49 (n)
  • 81.22 (a)
  • 78 (a)
(Mus musculus)
Mammalia Tpmt 35
  • 82.43 (n)
  • 79.08 (a)
Tpmt 16
Tpmt 36
  • 75 (a)
(Pan troglodytes)
Mammalia TPMT 35
  • 99.46 (n)
  • 99.18 (a)
  • 99 (a)
(Rattus norvegicus)
Mammalia Tpmt 35
  • 77.68 (n)
  • 72.8 (a)
(Monodelphis domestica)
Mammalia TPMT 36
  • 62 (a)
(Ornithorhynchus anatinus)
Mammalia TPMT 36
  • 57 (a)
(Gallus gallus)
Aves TPMT 35
  • 65.19 (n)
  • 58.85 (a)
  • 51 (a)
(Anolis carolinensis)
Reptilia TPMT 36
  • 48 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.12790 35
tpmt 35
  • 61.71 (n)
  • 49.55 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.24040 35
(Danio rerio)
Actinopterygii zgc:109981 35
  • 55.41 (n)
  • 53.07 (a)
TPMT (1 of 2) 36
  • 49 (a)
TPMT (2 of 2) 36
  • 51 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 34 (a)
-- 36
  • 35 (a)
-- 36
  • 35 (a)
Species with no ortholog for TPMT:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TPMT Gene

Gene Tree for TPMT (if available)
Gene Tree for TPMT (if available)

Paralogs for TPMT Gene

(1) SIMAP similar genes for TPMT Gene using alignment to 2 proteins: Pseudogenes for TPMT Gene

genes like me logo Genes that share paralogs with TPMT: view

No data available for Paralogs for TPMT Gene

Variants for TPMT Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for TPMT Gene

Individual variation in the toxicity and therapeutic efficacy of thiopurine drugs is associated with a common genetic polymorphism that controls levels of TPMT activity. Genetic polymorphism in the TPMT gene is such that about 90% of Caucasians have high TPMT activity, 10% have intermediate activity and 1 in 300 individuals has low activity. TPMT activity varies among ethnic groups.
TPMT*3A is the most common allele in the Caucasians and American Caucasians; it is the only mutant allele found in the South West Asians; it is not found in the Chinese. TPMT*3C is common in African-Americans and is the only allele in Chinese, Japanese and Taiwanese individuals. This allele is found at a low frequency in the Caucasians. This suggests that TPMT*3C is the oldest mutation, with TPMT*3B being acquired later to form the TPMT*3A allele in the Caucasian and South West Asian populations. TPMT*2 appears to be a more recent allele, which has only been detected in Caucasians to date. These ethnic differences may be important in the clinical use of thiopurine drugs.

Sequence variations from dbSNP and Humsavar for TPMT Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
rs72552740 - 18,147,910(+) TCTTT(A/G)ATAGC reference, missense
rs1800462 Thiopurine S-methyltransferase deficiency (TPMT deficiency) 18,143,724(-) GGTTT(C/G)CAGAC reference, missense
rs1800460 Thiopurine S-methyltransferase deficiency (TPMT deficiency) 18,138,997(-) GAGGA(A/G)CATTA reference, missense
rs75543815 - 18,133,845(+) GGAGA(A/T)ACTGA reference, missense
rs72552736 Thiopurine S-methyltransferase deficiency (TPMT deficiency) 18,130,725(+) CTTTT(A/C/T)TGTCG reference, missense

Structural Variations from Database of Genomic Variants (DGV) for TPMT Gene

Variant ID Type Subtype PubMed ID
nsv883460 CNV Gain 21882294
esv2731634 CNV Deletion 23290073

Variation tolerance for TPMT Gene

Residual Variation Intolerance Score: 79.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.95; 68.03% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TPMT Gene

Human Gene Mutation Database (HGMD)

Disorders for TPMT Gene

MalaCards: The human disease database

(16) MalaCards diseases for TPMT Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TPMT in MalaCards View complete list of genes associated with diseases


  • Thiopurine S-methyltransferase deficiency (TPMT deficiency) [MIM:610460]: Enzyme involved in the normal metabolic inactivation of thiopurine drugs. These drugs are generally used as immunosuppressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it is shown that inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus. {ECO:0000269 PubMed:10208641, ECO:0000269 PubMed:10751626, ECO:0000269 PubMed:15819814, ECO:0000269 PubMed:16220112, ECO:0000269 PubMed:16476125, ECO:0000269 PubMed:16789994, ECO:0000269 PubMed:7862671, ECO:0000269 PubMed:8561894, ECO:0000269 PubMed:8644731, ECO:0000269 PubMed:9246020, ECO:0000269 PubMed:9336428, ECO:0000269 PubMed:9711875, ECO:0000269 PubMed:9931345, ECO:0000269 PubMed:9931346}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for TPMT

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with TPMT: view

No data available for Genatlas for TPMT Gene

Publications for TPMT Gene

  1. Human thiopurine methyltransferase: molecular cloning and expression of T84 colon carcinoma cell cDNA. (PMID: 8316220) Honchel R. … Weinshilboum R.M. (Mol. Pharmacol. 1993) 2 3 4 23 67
  2. Clinical pharmacology and pharmacogenetics of thiopurines. (PMID: 18506437) Sahasranaman S. … Roy S. (Eur. J. Clin. Pharmacol. 2008) 23 25 26
  3. Determination of thiopurine methyltransferase activity in isolated human erythrocytes does not reflect putative in vivo enzyme inhibition by sulfasalazine. (PMID: 14752016) Shipkova M. … Wieland E. (Clin. Chem. 2004) 23 25 26
  4. Clinical implications of thiopurine methyltransferase--optimization of drug dosage and potential drug interactions. (PMID: 9780130) Lennard L. (Ther Drug Monit 1998) 23 25 26
  5. Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide. (PMID: 8866635) Lysaa R.A. … Aarbakke J. (Eur. J. Clin. Pharmacol. 1996) 23 25 26

Products for TPMT Gene

Sources for TPMT Gene