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 indi... See more...

Aliases for TPMT Gene

Aliases for TPMT Gene

  • Thiopurine S-Methyltransferase 2 3 4 5
  • EC 2.1.1.67 4 50
  • S-Adenosyl-L-Methionine:Thiopurine S-Methyltransferase 3
  • Thiopurine Methyltransferase 4
  • TPMTD 3
  • TPMT 5

External Ids for TPMT Gene

Previous GeneCards Identifiers for TPMT Gene

  • GC06M018186
  • GC06M018236
  • GC06M018072

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 Metabolism. Gene Ontology (GO) annotations related to this gene include S-adenosylmethionine-dependent methyltransferase activity and thiopurine S-methyltransferase activity.

UniProtKB/Swiss-Prot Summary for TPMT Gene

  • Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) and 6-thioguanine (also called tioguanine or 6-TG) using S-adenosyl-L-methionine as the methyl donor (PubMed:657528, PubMed:18484748). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified.

Gene Wiki entry for TPMT Gene

PharmGKB "VIP" Summary for TPMT Gene

No data available for CIViC Summary , Tocris Summary , Rfam classification and piRNA Summary for TPMT Gene

Genomics for TPMT Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TPMT Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J018152 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 270.6 +0.5 543 4.4 ZNF207 NCOR1 IKZF1 MYC ZNF600 SSRP1 JUND POLR2A CEBPA ZNF10 TPMT KDM1B NHLRC1 RNF144B RF00017-4846 HSALNG0048387
GH06J018146 Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 19.7 +7.0 7021 2.9 JUND ATF2 YY1 CEBPB ZNF513 EP300 KLF9 RXRA STAT3 ATF1 NHLRC1 TPMT KIF13A RNF144B KDM1B RF00017-4846 piR-50437-551 HSALNG0048387
GH06J018121 Promoter/Enhancer 1.6 Ensembl ENCODE CraniofacialAtlas 9.9 +32.5 32482 1.8 BCLAF1 SSRP1 KLF9 CEBPA YY1 MXD4 REST CTCF KLF11 CHD2 NHLRC1 piR-41306-225 TPMT RF00017-4845
GH06J018150 Enhancer 0.5 FANTOM5 Ensembl 21.4 +4.7 4666 1 ZNF10 SPI1 RF00017-4846 TPMT NHLRC1 KDM1B NUP153 piR-50437-551 HSALNG0048387
GH06J018177 Enhancer 0.9 Ensembl dbSUPER 10 -23.8 -23832 6.4 IKZF1 MAFF TAL1 ZNF316 MAFK ZBTB40 SPI1 FOXM1 HDAC2 FOXA1 TPMT NHLRC1 KDM1B piR-50852-134 HSALNG0048387 DEK
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TPMT on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TPMT

Top Transcription factor binding sites by QIAGEN in the TPMT gene promoter:
  • Pbx1a
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • SEF-1 (1)
  • SRF
  • SRF (504 AA)

Genomic Locations for TPMT Gene

Latest Assembly
chr6:18,128,311-18,155,169
(GRCh38/hg38)
Size:
26,859 bases
Orientation:
Minus strand

Previous Assembly
chr6:18,128,542-18,155,400
(GRCh37/hg19 by Entrez Gene)
Size:
26,859 bases
Orientation:
Minus strand

chr6:18,128,542-18,155,305
(GRCh37/hg19 by Ensembl)
Size:
26,764 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 Lys37
  • Modification sites at PhosphoSitePlus

Other Protein References for TPMT Gene

Domains & Families for TPMT Gene

Gene Families for TPMT Gene

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

Protein Domains for TPMT Gene

InterPro:
Blocks:
  • Thiopurine S-methyltransferase

Suggested Antigen Peptide Sequences for TPMT Gene

GenScript: Design optimal peptide antigens:
  • Thiopurine S-methyltransferase (Q9BS45_HUMAN)
  • Thiopurine methyltransferase (TPMT_HUMAN)

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

Function for TPMT Gene

Molecular function for TPMT Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) and 6-thioguanine (also called tioguanine or 6-TG) using S-adenosyl-L-methionine as the methyl donor (PubMed:657528, PubMed:18484748). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether.; EC=2.1.1.67; Evidence={ECO:0000269|PubMed:18484748, ECO:0000269|PubMed:657528};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=mercaptopurine + S-adenosyl-L-methionine = 6-methylthiopurine + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:12609, ChEBI:CHEBI:15378, ChEBI:CHEBI:28279, ChEBI:CHEBI:50667, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789; EC=2.1.1.67; Evidence={ECO:0000269|PubMed:18484748, ECO:0000269|PubMed:657528};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=6-thioguanine + S-adenosyl-L-methionine = 6-methylthioguanine + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:56580, ChEBI:CHEBI:9555, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:140528; EC=2.1.1.67; Evidence={ECO:0000269|PubMed:657528};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=18.5 uM for S-adenosyl-L-methionine (at pH 6.5 and 37 degrees Celsius) {ECO:0000269|PubMed:18484748}; KM=0.68 mM for 6-mercaptopurine (at pH 6.5 and 37 degrees Celsius) {ECO:0000269|PubMed:18484748}; KM=1.7 uM for S-adenosyl-L-methionine (at pH 7.5 and 37 degrees Celsius) {ECO:0000269|PubMed:657528}; KM=0.32 mM for 6-mercaptopurine (at pH 7.5 and 37 degrees Celsius) {ECO:0000269|PubMed:657528}; KM=0.20 mM for 6-thioguanine (at pH 7.5 and 37 degrees Celsius) {ECO:0000269|PubMed:657528}; Vmax=1.23 nmol/sec/mg enzyme toward 6-mercaptopurine (at pH 6.5 and 37 degrees Celsius) {ECO:0000269|PubMed:18484748}; pH dependence: Optimum pH is 7.5. {ECO:0000269|PubMed:657528};
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by S-adenosyl-L-homocysteine (SAH).
GENATLAS Biochemistry:
thiopurine methyltransferase,cytosolic,catalyzing the S-methylation of thiopurine drugs

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:0005515 protein binding IPI 32814053
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:
  • Tpmt Tpmt<tm1Rlng>

Animal Models for research

  • Taconic Biosciences Mouse Models for TPMT

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TPMT

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
cytosol 5
nucleus 3
plasma membrane 2
extracellular 2
mitochondrion 2
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TPMT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
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:0017144 drug metabolic process IDA 657528
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 237
Mercaptopurine Approved Pharma Enzyme, substrate 237
Bendroflumethiazide Approved Pharma Enzyme, inhibitor 7
Cefazolin Approved Pharma Enzyme, substrate 175
Olsalazine Approved Pharma Target, inhibitor 2

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
s-adenosylmethionine
  • (3S)-5'-[(3-Amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine, inner salt
  • [1-(Adenin-9-yl)-1,5-dideoxy-beta-D-ribofuranos-5-yl][(3S)-3-amino-3-carboxypropyl](methyl)sulfonium
  • Acylcarnitine
  • AdoMet
  • S-(5'-Deoxyadenosin-5'-yl)-L-methionine
485-80-3
6-Methylmercaptopurine
  • Thiopurine S-methylether
  • Methylmercaptopurine
  • 6-Methylmercaptopurine
  • 6-Methylthiopurine
6-Methylthioguanosine monophosphate
  • 6-Methylthioguanosine monophosphoric acid
6-Methylthiopurine 5'-monophosphate ribonucleotide
  • 6-Methylthioinosine-5'-monophosphate
  • 6-Methylthioinosine-5'-monophosphoric acid
  • 6-Methylthiopurine 5'-monophosphoric acid ribonucleotide
  • Methylthioinosine-5'-monophospate
  • Methylthioinosine 5'-monophospate
7021-52-5
6-Thioguanylic acid
  • 6-Thioguanosine monophosphoric acid
  • 6-TG Nucleotide
  • 6-Thioguanine nucleotide
  • 6-Thioguanosine-5'-phosphate
genes like me logo Genes that share compounds with TPMT: view

Transcripts for TPMT Gene

mRNA/cDNA for TPMT Gene

3 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products 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: -
SP5:
SP6: -
SP7: - -

Relevant External Links for TPMT Gene

GeneLoc Exon Structure 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, MaxQB, and MOPED for TPMT Gene



Protein tissue co-expression partners for TPMT Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TPMT

SOURCE GeneReport for Unigene cluster for TPMT Gene:

Hs.444319

Evidence on tissue expression from TISSUES for TPMT Gene

  • Liver(4.6)
  • Kidney(4.5)
  • Blood(4.5)
  • Bone marrow(4.4)
  • Nervous system(3.4)
  • Heart(2.3)
  • Intestine(2.3)
  • Thyroid gland(2.3)
  • Skin(2.3)
  • Spleen(2.1)

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

Germ Layers:
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • lymphatic
Regions:
Thorax:
  • thymus
Abdomen:
  • liver
  • spleen
General:
  • 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
Chimpanzee
(Pan troglodytes)
Mammalia TPMT 29 30
  • 99.46 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TPMT 29 30
  • 84.49 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TPMT 29 30
  • 84.08 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Tpmt 29 16 30
  • 82.43 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tpmt 29
  • 77.68 (n)
Oppossum
(Monodelphis domestica)
Mammalia TPMT 30
  • 62 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TPMT 30
  • 57 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TPMT 29 30
  • 65.19 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TPMT 30
  • 48 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia tpmt 29
  • 61.71 (n)
Str.12790 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.24040 29
Zebrafish
(Danio rerio)
Actinopterygii zgc:109981 29
  • 55.41 (n)
TPMT (2 of 2) 30
  • 51 (a)
OneToMany
TPMT (1 of 2) 30
  • 49 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 35 (a)
OneToMany
-- 30
  • 35 (a)
OneToMany
-- 30
  • 34 (a)
OneToMany
Species where no ortholog for TPMT was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for TPMT: view image
Alliance of Genome Resources:
Additional Orthologs for TPMT

Paralogs for TPMT Gene

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

  • TPMT_HUMAN
  • Q9BS45_HUMAN

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, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TPMT Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
rs1142345 Likely Benign, Other: Thiopurine methyltransferase deficiency; not provided 18,130,687(-) T/Cp.Tyr240Cys
NM_000367.4(TPMT):c.719A>G (p.Tyr240Cys)
MISSENSE
rs1256618794 Drug Response: Thiopurine response 18,143,728(-) C/A
NM_000367.4(TPMT):c.234G>T (p.Trp78Cys)
MISSENSE
rs1800460 Likely Benign, Other: Thiopurine methyltransferase deficiency; not provided 18,138,997(-) C/Tp.Ala154Thr
NM_000367.4(TPMT):c.460G>A (p.Ala154Thr)
MISSENSE
rs1800462 Drug Response: Thiopurine methyltransferase deficiency 18,143,724(-) C/Gp.Ala80Pro
NM_000367.2(TPMT):c.238G>C (p.Ala80Pro)
MISSENSE
rs1800584 Drug Response: Thiopurine methyltransferase deficiency 18,130,781(-) C/T
NM_000367.4(TPMT):c.626-1G>A
SPLICE_ACCEPTOR

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TPMT Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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)
TPMT
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TPMT
Leiden Open Variation Database (LOVD)
TPMT

SNP Genotyping and Copy Number Assays for research

Disorders for TPMT Gene

MalaCards: The human disease database

(24) MalaCards diseases for TPMT Gene - From: OMI, CVR, GTR, COP, and GCD

Disorder Aliases PubMed IDs
thiopurines, poor metabolism of, 1
  • thpm1
thiopurine s methyltranferase deficiency
  • 6-mercaptopurine sensitivity
autoimmune hepatitis
  • autoimmune chronic active hepatitis
pancytopenia
neutropenia
  • leukopenia
- 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

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
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 40 72
  2. Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population. (PMID: 10751626) Hiratsuka M … Mizugaki M (Mutation research 2000) 3 4 22 40 72
  3. 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 40
  4. The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. (PMID: 10208641) Collie-Duguid ES … McLeod HL (Pharmacogenetics 1999) 3 4 22 72
  5. Thiopurine methyltransferase alleles in British and Ghanaian populations. (PMID: 9931345) Ameyaw MM … McLeod HL (Human molecular genetics 1999) 3 4 22 72

Products for TPMT Gene

Sources for TPMT Gene