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Aliases for TPMT Gene

Aliases for TPMT Gene

  • Thiopurine S-Methyltransferase 2 3
  • EC 2.1.1.67 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 cisplatin toxicity and azathioprine or 6-mercatopurine toxicity or dose selection. Among its related pathways are Metabolism and Porphyrin and chlorophyll 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

No data available for Tocris Summary , PharmGKB "VIP" 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

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

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:
    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.
    Miscellaneous:
    • 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
    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

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

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 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 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
Jensen Localization Image for TPMT Gene COMPARTMENTS Subcellular localization image for TPMT gene
Compartment Confidence
extracellular 5
cytosol 4
peroxisome 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 & 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

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

No data available for SIGNOR curated interactions for TPMT Gene

Drugs & Compounds for TPMT Gene

(39) Drugs for TPMT Gene - From: NovoSeek, PharmGKB, ClinicalTrials, HMDB, and DrugBank

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Azathioprine Approved Pharma Enzyme, substrate 145
Mercaptopurine Approved Pharma Enzyme, substrate 0
Bendroflumethiazide Approved Pharma Enzyme, inhibitor 5
Cefazolin Approved Pharma Enzyme, substrate 97
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-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

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: -
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 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

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
cow
(Bos Taurus)
Mammalia TPMT 35
  • 84.08 (n)
  • 77.14 (a)
TPMT 36
  • 74 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TPMT 35
  • 84.49 (n)
  • 81.22 (a)
TPMT 36
  • 78 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tpmt 35
  • 82.43 (n)
  • 79.08 (a)
Tpmt 16
Tpmt 36
  • 75 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TPMT 35
  • 99.46 (n)
  • 99.18 (a)
TPMT 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tpmt 35
  • 77.68 (n)
  • 72.8 (a)
oppossum
(Monodelphis domestica)
Mammalia TPMT 36
  • 62 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TPMT 36
  • 57 (a)
OneToOne
chicken
(Gallus gallus)
Aves TPMT 35
  • 65.19 (n)
  • 58.85 (a)
TPMT 36
  • 51 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TPMT 36
  • 48 (a)
OneToOne
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
zebrafish
(Danio rerio)
Actinopterygii zgc:109981 35
  • 55.41 (n)
  • 53.07 (a)
TPMT (1 of 2) 36
  • 49 (a)
OneToMany
TPMT (2 of 2) 36
  • 51 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 34 (a)
OneToMany
-- 36
  • 35 (a)
OneToMany
-- 36
  • 35 (a)
OneToMany
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

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

P51580-TPMT_HUMAN
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, upstream-variant-2KB
rs1142345 Pathogenic, Pathogenic, 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

Variation tolerance for TPMT Gene

Residual Variation Intolerance Score: 79.21% 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

HapMap Linkage Disequilibrium report
TPMT
Human Gene Mutation Database (HGMD)
TPMT

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

Disorder Aliases PubMed IDs
cisplatin toxicity
azathioprine or 6-mercatopurine toxicity or dose selection
tpmt-related altered drug metabolism
  • 6-mercaptopurine sensitivity
6-mercaptopurine sensitivity
  • thiopurine methyltransferase deficiency
hypoprothrombinemia
  • dysprothrombinemia
- elite association
Search TPMT in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TPMT_HUMAN
  • 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)
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 Genatlas for TPMT Gene

Publications for TPMT Gene

  1. Clinical pharmacology and pharmacogenetics of thiopurines. (PMID: 18506437) Sahasranaman S. … Roy S. (Eur. J. Clin. Pharmacol. 2008) 23 25 26 67
  2. 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 67
  3. Clinical implications of thiopurine methyltransferase--optimization of drug dosage and potential drug interactions. (PMID: 9780130) Lennard L. (Ther Drug Monit 1998) 23 25 26 67
  4. 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 67
  5. Human thiopurine methyltransferase: molecular cloning and expression of T84 colon carcinoma cell cDNA. (PMID: 8316220) Honchel R. … Weinshilboum R.M. (Mol. Pharmacol. 1993) 2 23 67

Products for TPMT Gene

Sources for TPMT Gene

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