Details for: TPMT

Gene ID: 7172

Symbol: TPMT

Ensembl ID: ENSG00000137364

Description: thiopurine S-methyltransferase

Associated with

Cells (max top 100)

(Marker Score score is uniquely calculated using our advanced thresholding algorithms to reveal cell-specific gene markers)

  • Cell Name: thyroid follicular cell (CL0002258)
    Fold Change: 2.04
    Marker Score: 1595
  • Cell Name: epithelial cell of proximal tubule (CL0002306)
    Fold Change: 1.87
    Marker Score: 6633
  • Cell Name: enterocyte (CL0000584)
    Fold Change: 1.7
    Marker Score: 8148
  • Cell Name: mural cell (CL0008034)
    Fold Change: 1.47
    Marker Score: 168094
  • Cell Name: pancreatic acinar cell (CL0002064)
    Fold Change: 1.38
    Marker Score: 2909
  • Cell Name: colon epithelial cell (CL0011108)
    Fold Change: 1.3
    Marker Score: 4094
  • Cell Name: bladder urothelial cell (CL1001428)
    Fold Change: 1.24
    Marker Score: 1832
  • Cell Name: epithelial cell of urethra (CL1000296)
    Fold Change: 1.14
    Marker Score: 899
  • Cell Name: kidney proximal straight tubule epithelial cell (CL1000839)
    Fold Change: 1.07
    Marker Score: 2512
  • Cell Name: epithelial cell of esophagus (CL0002252)
    Fold Change: 1.03
    Marker Score: 8896
  • Cell Name: osteoclast (CL0000092)
    Fold Change: 1
    Marker Score: 500
  • Cell Name: cerebral cortex GABAergic interneuron (CL0010011)
    Fold Change: 1
    Marker Score: 71701
  • Cell Name: forebrain radial glial cell (CL0013000)
    Fold Change: 1
    Marker Score: 47924
  • Cell Name: NKp44-negative group 3 innate lymphoid cell, human (CL0001080)
    Fold Change: 0.99
    Marker Score: 218
  • Cell Name: absorptive cell (CL0000212)
    Fold Change: 0.98
    Marker Score: 30392
  • Cell Name: kidney loop of Henle thick ascending limb epithelial cell (CL1001106)
    Fold Change: 0.95
    Marker Score: 2555
  • Cell Name: mononuclear cell (CL0000842)
    Fold Change: 0.95
    Marker Score: 307
  • Cell Name: intestinal crypt stem cell of colon (CL0009043)
    Fold Change: 0.94
    Marker Score: 2399
  • Cell Name: tuft cell of colon (CL0009041)
    Fold Change: 0.93
    Marker Score: 479
  • Cell Name: BEST4+ intestinal epithelial cell, human (CL4030026)
    Fold Change: 0.92
    Marker Score: 434
  • Cell Name: transit amplifying cell (CL0009010)
    Fold Change: 0.92
    Marker Score: 5228
  • Cell Name: abnormal cell (CL0001061)
    Fold Change: 0.91
    Marker Score: 2726
  • Cell Name: cardiac muscle myoblast (CL0000513)
    Fold Change: 0.89
    Marker Score: 13953
  • Cell Name: enterocyte of epithelium of large intestine (CL0002071)
    Fold Change: 0.87
    Marker Score: 864
  • Cell Name: neoplastic cell (CL0001063)
    Fold Change: 0.86
    Marker Score: 5233
  • Cell Name: foveolar cell of stomach (CL0002179)
    Fold Change: 0.86
    Marker Score: 5506
  • Cell Name: Kupffer cell (CL0000091)
    Fold Change: 0.86
    Marker Score: 863
  • Cell Name: conjunctival epithelial cell (CL1000432)
    Fold Change: 0.86
    Marker Score: 903
  • Cell Name: choroid plexus epithelial cell (CL0000706)
    Fold Change: 0.85
    Marker Score: 781
  • Cell Name: epithelial cell of small intestine (CL0002254)
    Fold Change: 0.85
    Marker Score: 304
  • Cell Name: kidney collecting duct intercalated cell (CL1001432)
    Fold Change: 0.83
    Marker Score: 1378
  • Cell Name: alveolar macrophage (CL0000583)
    Fold Change: 0.82
    Marker Score: 20878
  • Cell Name: cell in vitro (CL0001034)
    Fold Change: 0.81
    Marker Score: 28176
  • Cell Name: proerythroblast (CL0000547)
    Fold Change: 0.81
    Marker Score: 551
  • Cell Name: stem cell (CL0000034)
    Fold Change: 0.8
    Marker Score: 1898
  • Cell Name: kidney collecting duct principal cell (CL1001431)
    Fold Change: 0.8
    Marker Score: 2007
  • Cell Name: kidney loop of Henle epithelial cell (CL1000909)
    Fold Change: 0.79
    Marker Score: 494
  • Cell Name: intestinal epithelial cell (CL0002563)
    Fold Change: 0.78
    Marker Score: 1265
  • Cell Name: acinar cell of salivary gland (CL0002623)
    Fold Change: 0.78
    Marker Score: 1775
  • Cell Name: Hofbauer cell (CL3000001)
    Fold Change: 0.78
    Marker Score: 429
  • Cell Name: early T lineage precursor (CL0002425)
    Fold Change: 0.77
    Marker Score: 591
  • Cell Name: kidney capillary endothelial cell (CL1000892)
    Fold Change: 0.77
    Marker Score: 242
  • Cell Name: small intestine goblet cell (CL1000495)
    Fold Change: 0.77
    Marker Score: 307
  • Cell Name: L5 extratelencephalic projecting glutamatergic cortical neuron (CL4023041)
    Fold Change: 0.76
    Marker Score: 1180
  • Cell Name: kidney cell (CL1000497)
    Fold Change: 0.76
    Marker Score: 506
  • Cell Name: precursor cell (CL0011115)
    Fold Change: 0.75
    Marker Score: 183
  • Cell Name: conventional dendritic cell (CL0000990)
    Fold Change: 0.75
    Marker Score: 515
  • Cell Name: CD14-positive, CD16-positive monocyte (CL0002397)
    Fold Change: 0.74
    Marker Score: 1451
  • Cell Name: type A enteroendocrine cell (CL0002067)
    Fold Change: 0.74
    Marker Score: 299
  • Cell Name: corneal epithelial cell (CL0000575)
    Fold Change: 0.74
    Marker Score: 813
  • Cell Name: dopaminergic neuron (CL0000700)
    Fold Change: 0.73
    Marker Score: 7546
  • Cell Name: intestine goblet cell (CL0019031)
    Fold Change: 0.73
    Marker Score: 698
  • Cell Name: paneth cell of colon (CL0009009)
    Fold Change: 0.73
    Marker Score: 209
  • Cell Name: Cajal-Retzius cell (CL0000695)
    Fold Change: 0.72
    Marker Score: 371
  • Cell Name: nephron tubule epithelial cell (CL1000494)
    Fold Change: 0.72
    Marker Score: 168
  • Cell Name: CD14-positive, CD16-negative classical monocyte (CL0002057)
    Fold Change: 0.71
    Marker Score: 39830
  • Cell Name: gut absorptive cell (CL0000677)
    Fold Change: 0.71
    Marker Score: 455
  • Cell Name: lung macrophage (CL1001603)
    Fold Change: 0.71
    Marker Score: 813
  • Cell Name: dendritic cell, human (CL0001056)
    Fold Change: 0.7
    Marker Score: 715
  • Cell Name: erythroid progenitor cell (CL0000038)
    Fold Change: 0.7
    Marker Score: 726
  • Cell Name: enterocyte of epithelium of small intestine (CL1000334)
    Fold Change: 0.7
    Marker Score: 2918
  • Cell Name: enterocyte of colon (CL1000347)
    Fold Change: 0.69
    Marker Score: 1069
  • Cell Name: stratified epithelial cell (CL0000079)
    Fold Change: 0.67
    Marker Score: 5270
  • Cell Name: CD14-positive monocyte (CL0001054)
    Fold Change: 0.67
    Marker Score: 1679
  • Cell Name: brush cell (CL0002204)
    Fold Change: 0.67
    Marker Score: 613
  • Cell Name: kidney loop of Henle thin ascending limb epithelial cell (CL1001107)
    Fold Change: 0.67
    Marker Score: 681
  • Cell Name: mucous neck cell (CL0000651)
    Fold Change: 0.67
    Marker Score: 1520
  • Cell Name: kidney epithelial cell (CL0002518)
    Fold Change: 0.67
    Marker Score: 708
  • Cell Name: L2/3-6 intratelencephalic projecting glutamatergic neuron (CL4023040)
    Fold Change: 0.67
    Marker Score: 41071
  • Cell Name: kidney distal convoluted tubule epithelial cell (CL1000849)
    Fold Change: 0.67
    Marker Score: 707
  • Cell Name: non-classical monocyte (CL0000875)
    Fold Change: 0.66
    Marker Score: 1605
  • Cell Name: neutrophil progenitor cell (CL0000834)
    Fold Change: 0.66
    Marker Score: 170
  • Cell Name: decidual cell (CL2000002)
    Fold Change: 0.66
    Marker Score: 2839
  • Cell Name: midzonal region hepatocyte (CL0019028)
    Fold Change: 0.66
    Marker Score: 2838
  • Cell Name: pancreatic ductal cell (CL0002079)
    Fold Change: 0.65
    Marker Score: 679
  • Cell Name: keratinocyte (CL0000312)
    Fold Change: 0.65
    Marker Score: 544
  • Cell Name: respiratory goblet cell (CL0002370)
    Fold Change: 0.65
    Marker Score: 188
  • Cell Name: pneumocyte (CL0000322)
    Fold Change: 0.65
    Marker Score: 1044
  • Cell Name: decidual natural killer cell, human (CL0002343)
    Fold Change: 0.64
    Marker Score: 1773
  • Cell Name: kidney connecting tubule epithelial cell (CL1000768)
    Fold Change: 0.64
    Marker Score: 903
  • Cell Name: granulocyte monocyte progenitor cell (CL0000557)
    Fold Change: 0.63
    Marker Score: 398
  • Cell Name: basal cell of prostate epithelium (CL0002341)
    Fold Change: 0.63
    Marker Score: 1530
  • Cell Name: B-1b B cell (CL0000821)
    Fold Change: 0.63
    Marker Score: 144
  • Cell Name: epithelial cell (CL0000066)
    Fold Change: 0.62
    Marker Score: 986
  • Cell Name: type II pneumocyte (CL0002063)
    Fold Change: 0.62
    Marker Score: 4031
  • Cell Name: kidney collecting duct cell (CL1001225)
    Fold Change: 0.62
    Marker Score: 121
  • Cell Name: peptic cell (CL0000155)
    Fold Change: 0.61
    Marker Score: 257
  • Cell Name: centrilobular region hepatocyte (CL0019029)
    Fold Change: 0.61
    Marker Score: 3936
  • Cell Name: lymphoid lineage restricted progenitor cell (CL0000838)
    Fold Change: 0.61
    Marker Score: 367
  • Cell Name: hepatocyte (CL0000182)
    Fold Change: 0.61
    Marker Score: 415
  • Cell Name: eye photoreceptor cell (CL0000287)
    Fold Change: 0.61
    Marker Score: 181
  • Cell Name: blood cell (CL0000081)
    Fold Change: 0.61
    Marker Score: 7051
  • Cell Name: paneth cell of epithelium of small intestine (CL1000343)
    Fold Change: 0.6
    Marker Score: 150
  • Cell Name: basal cell (CL0000646)
    Fold Change: 0.6
    Marker Score: 780
  • Cell Name: germ cell (CL0000586)
    Fold Change: 0.6
    Marker Score: 1055
  • Cell Name: CD1c-positive myeloid dendritic cell (CL0002399)
    Fold Change: 0.6
    Marker Score: 1564
  • Cell Name: pvalb GABAergic cortical interneuron (CL4023018)
    Fold Change: 0.6
    Marker Score: 22258
  • Cell Name: placental villous trophoblast (CL2000060)
    Fold Change: 0.6
    Marker Score: 2367
  • Cell Name: primitive red blood cell (CL0002355)
    Fold Change: 0.6
    Marker Score: 450
  • Cell Name: precursor B cell (CL0000817)
    Fold Change: 0.6
    Marker Score: 395

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Other Information

**Key Characteristics:** TPMT is a cytosolic enzyme belonging to the methionine adenosyltransferase (MAT) family. It is a dimeric protein composed of two subunits, each containing a catalytic domain. The enzyme is highly specific, with a substrate specificity for thiopurine drugs, such as azathioprine and mercaptopurine. TPMT is predominantly expressed in various tissues, including the thyroid, liver, kidneys, and intestinal epithelial cells. **Pathways and Functions:** TPMT is involved in the methylation of thiopurine drugs, converting them into inactive metabolites. This process involves the transfer of a methyl group from S-adenosylmethionine (SAMe) to the thiopurine molecule. The resulting metabolites are then excreted in the urine, thereby reducing the bioavailability of the parent compound. TPMT's primary function is to regulate the metabolism of thiopurine drugs, which is essential for maintaining their therapeutic efficacy while minimizing toxicity. **Clinical Significance:** TPMT plays a critical role in the treatment of various autoimmune and inflammatory diseases, including rheumatoid arthritis, Crohn's disease, and ulcerative colitis. However, the enzyme's activity can vary significantly among individuals, resulting in a range of therapeutic responses. Some patients may exhibit reduced TPMT activity, leading to increased thiopurine levels and toxicity, while others may have normal or elevated activity, resulting in reduced efficacy. Genetic variations in the TPMT gene have been identified as a significant factor in determining an individual's enzyme activity. These variations can result in reduced TPMT activity, leading to increased thiopurine levels and toxicity. Consequently, TPMT genotyping has become an essential tool in the clinical management of patients receiving thiopurine therapy. In addition to its role in thiopurine metabolism, TPMT has also been implicated in the regulation of other biological processes, including DNA methylation and histone modification. Dysregulation of TPMT activity has been linked to various diseases, including cancer, neurological disorders, and metabolic disorders. **Diseases and Disorders Associated with TPMT:** Reduced TPMT activity has been associated with various diseases, including: 1. **Thiopurine toxicity:** Increased thiopurine levels can lead to severe toxicity, including bone marrow suppression, liver damage, and gastrointestinal complications. 2. **Autoimmune diseases:** TPMT genotyping has been shown to predict the response to thiopurine therapy in patients with rheumatoid arthritis, Crohn's disease, and ulcerative colitis. 3. **Cancer:** TPMT has been implicated in the regulation of DNA methylation and histone modification, and dysregulation of the enzyme has been linked to various cancers, including colorectal and breast cancer. 4. **Neurological disorders:** Reduced TPMT activity has been associated with neurological disorders, including Parkinson's disease and multiple sclerosis. In conclusion, TPMT plays a crucial role in the metabolism of thiopurine drugs and modulates the efficacy and toxicity of these medications. Understanding the key characteristics, pathways, and functions of TPMT is essential for optimizing thiopurine therapy and minimizing adverse effects. Furthermore, TPMT genotyping has the potential to revolutionize the clinical management of patients with autoimmune and inflammatory diseases, allowing for personalized treatment approaches based on an individual's enzyme activity.

Genular Protein ID: 894094893

Symbol: TPMT_HUMAN

Name: N/A

UniProtKB Accession Codes:

P51580 O14806 O15423 O15424 O15425 O15426 O15515 O15548 O43213 Q5VUK6 Q9UBE6 Q9UBT8 Q9UE62

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 15 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 6 DrugCentral 1 EC 3 EMBL 33 EPD 1 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 Genevisible 1 GenomeRNAi 1 GlyGen 1 HAMAP 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 2 MalaCards 1 MassIVE 1 MaxQB 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 2 PIR 1 PIRSF 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 3 RefSeq 3 Rhea 2 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8316220

Title: Human thiopurine methyltransferase: molecular cloning and expression of T84 colon carcinoma cell cDNA.

PubMed ID: 8316220

PubMed ID: 7628307

Title: Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1.

PubMed ID: 7628307

PubMed ID: 8561894

Title: Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism.

PubMed ID: 8561894

DOI: 10.1089/dna.1996.15.17

PubMed ID: 9453052

Title: Promoter and intronic sequences of the human thiopurine S-methyltransferase (TPMT) gene isolated from a human PAC1 genomic library.

PubMed ID: 9453052

DOI: 10.1023/a:1012111325397

PubMed ID: 9246020

Title: Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms.

PubMed ID: 9246020

DOI: 10.1016/s0009-9236(97)90152-1

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9711875

Title: Detection of known and new mutations in the thiopurine S-methyltransferase gene by single-strand conformation polymorphism analysis.

PubMed ID: 9711875

DOI: 10.1002/(sici)1098-1004(1998)12:3<177::aid-humu5>3.0.co;2-e

PubMed ID: 657528

Title: Human erythrocyte thiopurine methyltransferase: radiochemical microassay and biochemical properties.

PubMed ID: 657528

DOI: 10.1016/0009-8981(78)90311-x

PubMed ID: 18484748

Title: Structural basis of substrate recognition in thiopurine S-methyltransferase.

PubMed ID: 18484748

DOI: 10.1021/bi800102x

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 18318008

Title: Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography.

PubMed ID: 18318008

DOI: 10.1002/pmic.200700884

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 19608861

Title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

PubMed ID: 19608861

DOI: 10.1126/science.1175371

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 17243178

Title: Structural basis of allele variation of human thiopurine-S-methyltransferase.

PubMed ID: 17243178

DOI: 10.1002/prot.21272

PubMed ID: 7862671

Title: A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase.

PubMed ID: 7862671

DOI: 10.1073/pnas.92.4.949

PubMed ID: 8644731

Title: Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians.

PubMed ID: 8644731

PubMed ID: 9336428

Title: Azathioprine-induced severe pancytopenia due to a homozygous two-point mutation of the thiopurine methyltransferase gene in a patient with juvenile HLA-B27-associated spondylarthritis.

PubMed ID: 9336428

DOI: 10.1002/art.1780401026

PubMed ID: 9177237

Title: 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.

PubMed ID: 9177237

DOI: 10.1073/pnas.94.12.6444

PubMed ID: 9931345

Title: Thiopurine methyltransferase alleles in British and Ghanaian populations.

PubMed ID: 9931345

DOI: 10.1093/hmg/8.2.367

PubMed ID: 9931346

Title: Polymorphism of the thiopurine S-methyltransferase gene in African-Americans.

PubMed ID: 9931346

DOI: 10.1093/hmg/8.2.371

PubMed ID: 10208641

Title: The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations.

PubMed ID: 10208641

DOI: 10.1097/00008571-199902000-00006

PubMed ID: 10751626

Title: Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population.

PubMed ID: 10751626

DOI: 10.1016/s0027-5107(00)00004-x

PubMed ID: 16220112

Title: Thiopurine S-methyltransferase pharmacogenetics: variant allele functional and comparative genomics.

PubMed ID: 16220112

DOI: 10.1097/01.fpc.0000174788.69991.6b

PubMed ID: 15819814

Title: Severe azathioprine-induced myelotoxicity in a kidney transplant patient with thiopurine S-methyltransferase-deficient genotype (TPMT*3A/*3C).

PubMed ID: 15819814

DOI: 10.1111/j.1432-2277.2005.00095.x

PubMed ID: 16476125

Title: Molecular analysis of thiopurine S-methyltransferase alleles in Taiwan aborigines and Taiwanese.

PubMed ID: 16476125

DOI: 10.1111/j.1365-2710.2006.00707.x

PubMed ID: 16789994

Title: Frequency of the thiopurine S-methyltransferase alleles in the ancient genetic population isolate of Sardinia.

PubMed ID: 16789994

DOI: 10.1111/j.1365-2710.2006.00736.x

Sequence Information:

  • Length: 245
  • Mass: 28180
  • Checksum: 190E781155B97BB9
  • Sequence:
    • MDGTRTSLDI EEYSDTEVQK NQVLTLEEWQ DKWVNGKTAF HQEQGHQLLK KHLDTFLKGK 
SGLRVFFPLC GKAVEMKWFA DRGHSVVGVE ISELGIQEFF TEQNLSYSEE PITEIPGTKV 
FKSSSGNISL YCCSIFDLPR TNIGKFDMIW DRGALVAINP GDRKCYADTM FSLLGKKFQY 
LLCVLSYDPT KHPGPPFYVP HAEIERLFGK ICNIRCLEKV DAFEERHKSW GIDCLFEKLY 
LLTEK

Database document:

This is a preview of the gene's schema. Only a few entries are kept for 'singleCellExpressions,' 'mRNAExpressions,' and other large data arrays for visualization purposes. For the full schema, download it here.