Browse TPMT

Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm.
Domain PF05724 Thiopurine S-methyltransferase (TPMT)
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.

> Gene Ontology
 
Biological Process GO:0032259 methylation
Molecular Function GO:0008119 thiopurine S-methyltransferase activity
GO:0008168 methyltransferase activity
GO:0008172 S-methyltransferase activity
GO:0008757 S-adenosylmethionine-dependent methyltransferase activity
GO:0016741 transferase activity, transferring one-carbon groups
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa00983 Drug metabolism - other enzymes
Reactome R-HSA-211859: Biological oxidations
R-HSA-1430728: Metabolism
R-HSA-156581: Methylation
R-HSA-156580: Phase II conjugation
Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TPMT and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.

Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of TPMT in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of TPMT in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.6650.0273
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.9750.635
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.4380.775
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0330.93
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1330.917
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2420.877
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.2390.542
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.2490.888
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2490.9
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.010.995
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.0770.972
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.090.303
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TPMT in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TPMT. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TPMT. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TPMT.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TPMT. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TPMT expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TPMT and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTPMT
Namethiopurine S-methyltransferase
Aliases S-adenosyl-L-methionine:thiopurine S-methyltransferase; Thiopurine methyltransferase
Chromosomal Location6p22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TPMT collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting TPMT.
ID Name Drug Type Targets #Targets
DB01250OlsalazineSmall MoleculeIFNG, TPMT2