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Aliases for TPMT Gene

Aliases for TPMT Gene

  • Thiopurine S-Methyltransferase 2 3 5
  • EC 2.1.1.67 4 61
  • 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 Cytochrome P450 - arranged by substrate type and Metabolism. 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 Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH06F018152 1.5 FANTOM5 ENCODE 20.7 +0.6 595 4.2 HDGF PKNOX1 ARNT CREB3L1 ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 TPMT NHLRC1 RNF144B KDM1B
GH06F018146 1.4 FANTOM5 Ensembl ENCODE 19.7 +7.2 7198 2.5 PKNOX1 ATF1 JUN CEBPG YY1 IRF9 SCRT2 HNF4G FOS KLF8 NHLRC1 TPMT KIF13A RNF144B KDM1B
GH06F018121 1 ENCODE 9.8 +32.6 32619 1.5 ATF1 MLX ARID4B SIN3A DMAP1 ZNF48 YY1 SLC30A9 ZNF143 FOS NHLRC1 TPMT GC06P018054
GH06F018184 0.8 Ensembl ENCODE 10.1 -30.7 -30740 2.6 MTA2 BCL11A ZNF341 FEZF1 ZIC2 NHLRC1 TPMT KDM1B DEK
GH06F018178 0.6 Ensembl 10 -24.5 -24536 1.8 ZNF316 MAFF MAFG EMSY MAFK TPMT KDM1B DEK
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

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
ENSR00001212736 -135 2601 HDGF PKNOX1 ARNT CREB3L1 ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF766

Genomic Location for TPMT Gene

Chromosome:
6
Start:
18,128,311 bp from pter
End:
18,155,165 bp from pter
Size:
26,855 bases
Orientation:
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:
    P51580-TPMT_HUMAN
    Recommended name:
    Thiopurine S-methyltransferase
    Protein Accession:
    P51580
    Secondary Accessions:
    • O14806
    • O15423
    • O15424
    • O15425
    • O15426
    • O15515
    • O15548
    • O43213
    • Q5VUK6
    • Q9UBE6
    • Q9UBT8
    • Q9UE62

    Protein attributes for TPMT Gene

    Size:
    245 amino acids
    Molecular mass:
    28180 Da
    Quaternary structure:
    • Monomer.
    SequenceCaution:
    • 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

P51580:
  • EVQKNQVLTLE
  • EEPITEIPG
  • IWDRGALVA
  • FHQEQGH
  • FKSSSGNISLYCC
  • GPPFYVP
  • TEIPGTK
  • NPGDRKCY
  • LDTFLKG
  • VLTLEEW
  • VVGVEISE
  • LRVFFPLCGKAVEMKWFA
  • SYDPTKH
  • EMKWFADRGH

Post-translational modifications for TPMT Gene

  • Ubiquitination at Lys 37
  • Modification sites at PhosphoSitePlus

Other Protein References for TPMT Gene

Antibody Products

  • Santa Cruz Biotechnology (SCBT) Antibodies for TPMT

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

P51580

UniProtKB/Swiss-Prot:

TPMT_HUMAN :
  • Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.
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 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

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

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for TPMT

Flow Cytometry Products

No data available for Transcription Factor Targets and HOMER Transcription for TPMT Gene

Localization for TPMT Gene

Subcellular locations from UniProtKB/Swiss-Prot for TPMT Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
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 IDA 23376485
genes like me logo Genes that share ontologies with TPMT: view

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

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

(50) 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 165
Mercaptopurine Approved Pharma Enzyme, substrate 0
Bendroflumethiazide Approved Pharma Enzyme, inhibitor 5
Cefazolin Approved Pharma Enzyme, substrate 106
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
6-Methylmercaptopurine
6-Methylthioguanosine monophosphate
6-Methylthiopurine 5'-monophosphate ribonucleotide
6-Thioguanosine monophosphate
6-Thioinosine-5'-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:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids 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: -
SP5:
SP6: -
SP7: - -

Relevant External Links for TPMT Gene

GeneLoc Exon Structure for
TPMT
ECgene alternative splicing isoforms for
TPMT

Expression for TPMT Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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:

TPMT

SOURCE GeneReport for Unigene cluster for TPMT Gene:

Hs.444319
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
chimpanzee
(Pan troglodytes)
Mammalia TPMT 34 35
  • 99.46 (n)
dog
(Canis familiaris)
Mammalia TPMT 34 35
  • 84.49 (n)
cow
(Bos Taurus)
Mammalia TPMT 34 35
  • 84.08 (n)
mouse
(Mus musculus)
Mammalia Tpmt 34 16 35
  • 82.43 (n)
rat
(Rattus norvegicus)
Mammalia Tpmt 34
  • 77.68 (n)
oppossum
(Monodelphis domestica)
Mammalia TPMT 35
  • 62 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TPMT 35
  • 57 (a)
OneToOne
chicken
(Gallus gallus)
Aves TPMT 34 35
  • 65.19 (n)
lizard
(Anolis carolinensis)
Reptilia TPMT 35
  • 48 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tpmt 34
  • 61.71 (n)
Str.12790 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.24040 34
zebrafish
(Danio rerio)
Actinopterygii zgc:109981 34
  • 55.41 (n)
TPMT (2 of 2) 35
  • 51 (a)
OneToMany
TPMT (1 of 2) 35
  • 49 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 35 (a)
OneToMany
-- 35
  • 35 (a)
OneToMany
-- 35
  • 34 (a)
OneToMany
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

ENSEMBL:
Gene Tree for TPMT (if available)
TreeFam:
Gene Tree for TPMT (if available)

Paralogs for TPMT Gene

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

Pseudogenes.org 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

TPMT_HUMAN-P51580
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_HUMAN-P51580
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 Sequence Context AA Info Type
rs1142345 drug-response 18,130,687(-) GTTAT(A/G)TCTAC reference, missense
rs1800460 drug-response 18,138,997(-) GAGGA(A/G)CATTA reference, missense
rs1800462 drug-response 18,143,724(-) GGTTT(C/G)CAGAC reference, missense
rs1800584 drug-response 18,130,781(-) TTTCA(A/G)GTAAA splice-acceptor-variant
rs56019966 drug-response 18,139,041(+) TCCTA(C/T)CAGAA intron-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)

Relevant External Links for TPMT Gene

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

Disorders for TPMT Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
6-mercaptopurine sensitivity
  • thiopurine s-methyltransferase deficiency
tpmt-related altered drug metabolism
  • 6-mercaptopurine sensitivity
pancytopenia
  • pancytopenia nos
azathioprine or 6-mercatopurine toxicity or dose selection
hearing loss, cisplatin-induced
  • hearing loss, cisplatin-induced, susceptibility to
- elite association - COSMIC cancer census association via MalaCards
Search TPMT in MalaCards View complete list of genes associated with diseases

Relevant External Links for TPMT

Genetic Association Database (GAD)
TPMT
Human Genome Epidemiology (HuGE) Navigator
TPMT
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TPMT
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 H.-F. … Chang J.-G. (J. Clin. Pharm. Ther. 2006) 3 4 22 46 64
  2. 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 22 46 64
  3. Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population. (PMID: 10751626) Hiratsuka M. … Mizugaki M. (Mutat. Res. 2000) 3 4 22 46 64
  4. 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 22 64
  5. MTHFR and TYMS genotypes influence TPMT activity and its differential modulation in males and females. (PMID: 19748501) Karas-Kuzelicki N. … Mlinaric-Rascan I. (Clin. Biochem. 2010) 3 22 46 64

Products for TPMT Gene

  • Cloud-Clone Corp. Antibodies for TPMT
  • Cloud-Clone Corp. Proteins for TPMT
  • Cloud-Clone Corp Assay Kits for TPMT

Sources for TPMT Gene

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