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Aliases for TPMT Gene

Aliases for TPMT Gene

  • Thiopurine S-Methyltransferase 2 3 5
  • EC 4 56
  • 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 Thiopurines, Poor Metabolism Of, 1 and Thiopurine S Methyltranferase Deficiency. Among its related pathways are Cytochrome P450 - arranged by substrate type and Drug metabolism - cytochrome P450. Gene Ontology (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

Additional gene information for TPMT Gene

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

Genomics for TPMT Gene

GeneHancer (GH) Regulatory Elements for TPMT Gene

Promoters and enhancers for TPMT Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06I018152 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 570.7 +0.6 595 4.2 HDGF FOXA2 PKNOX1 SMAD1 ARNT ZFP64 ARID4B SIN3A DMAP1 ZNF2 TPMT KDM1B NHLRC1 RNF144B
GH06I018146 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 19.7 +7.2 7197 2.5 PKNOX1 ATF1 YY1 SCRT2 FOS ATF7 CREM SP5 CEBPB ZEB2 NHLRC1 TPMT KIF13A RNF144B KDM1B
GH06I018121 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 9.8 +32.6 32618 1.5 CLOCK FOXA2 MLX ARID4B SIN3A DMAP1 ZNF48 YY1 TCF12 SLC30A9 NHLRC1 TPMT GC06P018054
GH06I018164 Enhancer 0.6 dbSUPER 17 -11.4 -11412 4.5 BCOR ZNF146 ZNF280D MAFG ZMYM3 ZNF316 ADNP ZNF24 EMSY MAFK NHLRC1 TPMT KDM1B DEK
GH06I018184 Enhancer 0.9 Ensembl ENCODE dbSUPER 10.1 -30.7 -30739 2.6 SP1 ZNF341 SIN3A HNF4A FEZF1 ZIC2 NHLRC1 TPMT KDM1B DEK
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around TPMT on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TPMT gene promoter:

Genomic Locations for TPMT Gene

Genomic Locations for TPMT Gene
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.
    • 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

Selected DME Specific Peptides for TPMT Gene


Post-translational modifications for TPMT Gene

  • Ubiquitination at isoforms=37
  • Modification sites at PhosphoSitePlus

Other Protein References for TPMT Gene

Domains & Families for TPMT Gene

Gene Families for TPMT Gene

Human Protein Atlas (HPA):
  • Enzymes
  • FDA approved drug targets
  • Predicted intracellular proteins

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

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

Phenotypes From GWAS Catalog 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 TAS --
GO:0008168 methyltransferase activity IEA --
GO:0008757 S-adenosylmethionine-dependent methyltransferase activity IEA --
GO:0016740 transferase activity IEA --
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

  • Taconic Biosciences Mouse Models for TPMT

Clone Products

  • Addgene plasmids for TPMT

No data available for Human Phenotype Ontology , 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

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TPMT gene
Compartment Confidence
extracellular 5
cytosol 5
nucleus 2

Gene Ontology (GO) - Cellular Components for TPMT Gene

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

No data available for Subcellular locations from the Human Protein Atlas (HPA) 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

2 BioSystems pathways 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:0006139 nucleobase-containing compound metabolic process TAS 8316220
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

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Azathioprine Approved Pharma Enzyme, substrate 190
Mercaptopurine Approved Pharma Enzyme, substrate 0
Bendroflumethiazide Approved Pharma Enzyme, inhibitor 5
Cefazolin Approved Pharma Enzyme, substrate 126
Olsalazine Approved Pharma Target, inhibitor 1

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • (3S)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine
  • 2-S-Adenosyl-L-methionine
  • 5'-Deoxyadenosine-5'-L-methionine disulfate ditosylate
  • 5'-Deoxyadenosine-5'-L-methionine disulphate ditosylate
  • Active methionine
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

Unigene Clusters for TPMT Gene

Thiopurine S-methyltransferase:
Representative Sequences:

Clone Products

  • Addgene plasmids for TPMT

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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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, MaxQB, and MOPED for TPMT Gene

Protein tissue co-expression partners for TPMT Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of TPMT Gene:


SOURCE GeneReport for Unigene cluster for TPMT Gene:


Evidence on tissue expression from TISSUES for TPMT Gene

  • Liver(4.5)
  • Kidney(4.4)
  • Bone marrow(4.3)
  • Nervous system(2.7)
  • Blood(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TPMT Gene

Germ Layers:
  • mesoderm
  • cardiovascular
  • digestive
  • immune
  • lymphatic
  • thymus
  • liver
  • spleen
  • blood
  • bone marrow
  • coagulation system
  • red blood cell
  • white blood cell
genes like me logo Genes that share expression patterns with TPMT: view

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
(Pan troglodytes)
Mammalia TPMT 33 34
  • 99.46 (n)
(Canis familiaris)
Mammalia TPMT 33 34
  • 84.49 (n)
(Bos Taurus)
Mammalia TPMT 33 34
  • 84.08 (n)
(Mus musculus)
Mammalia Tpmt 33 16 34
  • 82.43 (n)
(Rattus norvegicus)
Mammalia Tpmt 33
  • 77.68 (n)
(Monodelphis domestica)
Mammalia TPMT 34
  • 62 (a)
(Ornithorhynchus anatinus)
Mammalia TPMT 34
  • 57 (a)
(Gallus gallus)
Aves TPMT 33 34
  • 65.19 (n)
(Anolis carolinensis)
Reptilia TPMT 34
  • 48 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia tpmt 33
  • 61.71 (n)
Str.12790 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.24040 33
(Danio rerio)
Actinopterygii zgc:109981 33
  • 55.41 (n)
TPMT (2 of 2) 34
  • 51 (a)
TPMT (1 of 2) 34
  • 49 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 35 (a)
-- 34
  • 35 (a)
-- 34
  • 34 (a)
Species where no ortholog for TPMT was found in the sources mined by GeneCards:
  • 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

Polymorphic variations define TPMT activity levels that are variable among ethnic groups. 90% of Caucasians have high TPMT activity, 10% have intermediate activity, and 1 in 300 individuals has low activity (PubMed:10208641). These differences influence the clinical use and therapeutic efficacy of thiopurine drugs, generally used as immunosuppressants or cytotoxic drugs in conditions including leukemia, autoimmune disease and organ transplantation. Intermediate or low TPMT activity is associated with thiopurine intolerance and patients are at risk of toxicity after receiving standard doses of thiopurine drugs [MIM:610460] (PubMed:10751626, PubMed:15819814, PubMed:16220112, PubMed:16476125, PubMed:16789994, PubMed:7862671, PubMed:8561894, PubMed:8644731, PubMed:9246020, PubMed:9336428, PubMed:9711875, PubMed:9931345, PubMed:9931346). The most prevalent TPMT alleles associated with TPMT deficiency are TPMT*2 and TPMT*3A. The proteins encoded by TPMT*2 and TPMT*3A mutant are degraded more rapidly by an ATP-dependent proteasome-mediated pathway (PubMed:9177237, PubMed:8644731).
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.

Sequence variations from dbSNP and Humsavar for TPMT Gene

SNP ID Clin Chr 06 pos Variation AA Info Type
rs1026134461 uncertain-significance, Thiopurine methyltransferase deficiency 18,129,078(-) A/G 3_prime_UTR_variant
rs1142345 drug-response, other, Thiopurine methyltransferase deficiency, not provided 18,130,687(-) T/C/G coding_sequence_variant, missense_variant
rs1142374 uncertain-significance, Thiopurine methyltransferase deficiency 18,128,848(-) T/C 3_prime_UTR_variant
rs1142378 likely-benign, Thiopurine methyltransferase deficiency 18,128,768(-) T/G 3_prime_UTR_variant
rs116170115 uncertain-significance, Thiopurine methyltransferase deficiency 18,129,146(-) G/A 3_prime_UTR_variant

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

Variant ID Type Subtype PubMed ID
esv2731634 CNV deletion 23290073
nsv1034755 CNV loss 25217958
nsv601049 CNV gain 21841781
nsv601050 CNV gain 21841781

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)

Additional Variant Information for TPMT Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

Disorders for TPMT Gene

MalaCards: The human disease database

(13) MalaCards diseases for TPMT Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

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

Additional Disease Information for TPMT

Genetic Association Database
Human Genome Epidemiology 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 UniProtKB/Swiss-Prot and Genatlas for TPMT Gene

Publications for TPMT Gene

  1. Molecular analysis of thiopurine S-methyltransferase alleles in Taiwan aborigines and Taiwanese. (PMID: 16476125) Lu HF … Chang JG (Journal of clinical pharmacy and therapeutics 2006) 3 4 22 44 58
  2. Frequency of the thiopurine S-methyltransferase alleles in the ancient genetic population isolate of Sardinia. (PMID: 16789994) Rossino R … Congia M (Journal of clinical pharmacy and therapeutics 2006) 3 4 22 44 58
  3. Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population. (PMID: 10751626) Hiratsuka M … Mizugaki M (Mutation research 2000) 3 4 22 44 58
  4. Human thiopurine methyltransferase: molecular cloning and expression of T84 colon carcinoma cell cDNA. (PMID: 8316220) Honchel R … Weinshilboum RM (Molecular pharmacology 1993) 2 3 4 22 58
  5. Thiopurine S-methyltransferase genotype and the use of thiopurines in paediatric inflammatory bowel disease Greek patients. (PMID: 20175817) Gazouli M … Roma-Giannikou E (Journal of clinical pharmacy and therapeutics 2010) 3 22 44 58

Products for TPMT Gene

  • Addgene plasmids for TPMT

Sources for TPMT Gene

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