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Aliases for TPMT Gene

Aliases for TPMT Gene

  • Thiopurine S-Methyltransferase 2 3
  • EC 4 63
  • Thiopurine Methyltransferase 4

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 azathioprine or 6-mercatopurine toxicity or dose selection. Among its related pathways are Metabolism and Glucuronidation. GO annotations related to this gene include 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

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for TPMT Gene

18,128,311 bp from pter
18,155,143 bp from pter
26,833 bases
Minus strand

Genomic View for TPMT Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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 Lys37
  • Modification sites at PhosphoSitePlus

Other Protein References for TPMT Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

Domains 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

Gene Ontology (GO) - Molecular Function for TPMT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008119 thiopurine S-methyltransferase activity IEA --
GO:0008757 S-adenosylmethionine-dependent methyltransferase activity --
genes like me logo Genes that share ontologies with TPMT: view
genes like me logo Genes that share phenotypes with TPMT: view

Animal Models for TPMT Gene

MGI Knock Outs for TPMT:

Animal Model Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TPMT

In Situ Assay Products

Flow Cytometry Products

No data available for miRNA , 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 4
nucleus 2
extracellular 1

Gene Ontology (GO) - Cellular Components for TPMT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0070062 extracellular exosome IDA 23376485
genes like me logo Genes that share ontologies with TPMT: view

Pathways 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

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

Interacting Proteins for TPMT Gene

Gene Ontology (GO) - Biological Process for TPMT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006139 nucleobase-containing compound metabolic process TAS 8316220
GO:0006805 xenobiotic metabolic process TAS --
GO:0032259 methylation TAS --
GO:0044281 small molecule metabolic process TAS --
genes like me logo Genes that share ontologies with TPMT: view

Drugs for TPMT Gene

(6) Drugbank Compounds for TPMT Gene

Compound Status Synonyms Cas Number PubChem ID Type Actions PubMed IDs
  • 6-((1-Methyl-4-nitro-1H-imidazol-5-yl)thio)-1H-purine
446-86-6 2265 Enzyme substrate approved
  • +--3-Benzyl-3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
73-48-3 2315 Enzyme inhibitor approved
  • (6R,7R)-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-8-oxo-7-[(1H-tetrazol-1-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
25953-19-9 Enzyme substrate approved
  • 1,7-Dihydro-6H-purine-6-thione
50-44-2 667490 Enzyme substrate approved
  • Dipentum
15722-48-2 6003770 Target inhibitor approved

(50) Novoseek inferred chemical compound relationships for TPMT Gene

Compound -log(P) Hits PubMed IDs
thiopurine 99.6 341
6 mercaptopurine 97.4 224
6-thioguanine nucleotide 93.7 27
6 thioguanine 92.6 84
6-methylthioguanine 91.8 11

(7) PharmGKB related drug/compound annotations for TPMT Gene

Drug/compound Annotation
azathioprine DosingGuideline,DrugLabel,Clinical Annotation
cisplatin DosingGuideline,DrugLabel,Clinical Annotation
cyclophosphamide DosingGuideline,DrugLabel,Clinical Annotation
mercaptopurine DosingGuideline,DrugLabel,Clinical Annotation
olanzapine DosingGuideline,DrugLabel,Clinical Annotation
purine analogues DosingGuideline,DrugLabel,Clinical Annotation
thioguanine DosingGuideline,DrugLabel,Clinical Annotation
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:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TPMT

Flow Cytometry Products

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 for TPMT Gene

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

Integrated Proteomics: protein expression 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 expressions with TPMT: view

Expression partners for TPMT Gene

* - Elite partner

Primer Products

In Situ Assay 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

Sequence variations from dbSNP and Humsavar for TPMT Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs7886 -- 18,128,428(+) ATAAA(A/T)GATCA utr-variant-3-prime
rs968338 -- 18,150,072(-) GGAGG(G/T)AAATC intron-variant
rs1142345 Pathogenic, Thiopurine S-methyltransferase deficiency (TPMT deficiency) 18,130,687(-) GTTAT(A/G)TCTAC reference, missense
rs1142346 -- 18,130,246(-) gtgca(A/G)tggtg utr-variant-3-prime
rs1142347 -- 18,130,239(-) ggtgc(A/G)atctc utr-variant-3-prime

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

Relevant External Links for TPMT Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

Disorders for TPMT Gene

(1) OMIM Diseases for TPMT Gene (187680)


  • 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.

(47) Novoseek inferred disease relationships for TPMT Gene

Disease -log(P) Hits PubMed IDs
inflammatory bowel diseases 80.8 84
leukopenia 70 37
lymphoblastic leukemia acute 69.2 25
lymphoblastic leukemia acute childhood 65.7 7
colitis ulcerative 61.6 12

Relevant External Links for TPMT

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
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
  2. Molecular analysis of thiopurine S-methyltransferase alleles in Taiwan aborigines and Taiwanese. (PMID: 16476125) Lu H.-F. … Chang J.-G. (J. Clin. Pharm. Ther. 2006) 3 4 23 48
  3. Frequency of the thiopurine S-methyltransferase alleles in the ancient genetic population isolate of Sardinia. (PMID: 16789994) Rossino R. … Congia M. (J. Clin. Pharm. Ther. 2006) 3 4 23 48
  4. Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population. (PMID: 10751626) Hiratsuka M. … Mizugaki M. (Mutat. Res. 2000) 3 4 23 48
  5. 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. (PMID: 9177237) Tai H.-L. … Evans W.E. (Proc. Natl. Acad. Sci. U.S.A. 1997) 3 4 23

Products for TPMT Gene

Sources for TPMT Gene

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