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Tchem
TPMT
Thiopurine S-methyltransferase

Protein Summary
Description
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. 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]
Illumination Graph
Knowledge Table
Most Knowledge About
Knowledge Value (0 to 1 scale)
disease perturbation
0.95
biological term
0.86
histone modification site profile
0.82
transcription factor perturbation
0.74
disease
0.7


Related Tools
Target Illumination GWAS Analytics (TIGA)
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TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.
GENEVA
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GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.
GlyGen
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GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.
IDG Development Level Summary
Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 406.12   (req: < 5)
Gene RIFs: 157   (req: <= 3)
Antibodies: 384   (req: <= 50)
Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 406.12   (req: >= 5)
Gene RIFs: 157   (req: > 3)
Antibodies: 384   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 5
Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2
Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0
GWAS Traits (7)
GWAS Trait
EFO ID
Study Count
SNP Count
Beta Count
Odds Ratio
Evidence (Mean Rank Score)
Provenance
response to mercaptopurine
1
1
0
7.7
85.5
thiopurine methyltransferase activity measurement
1
1
0
7.7
85.5
2
1
0
1.1
77
1
1
0
5.6
21.5
age at onset
1
1
0
5.6
21.5
GWAS Trait
EFO ID
Beta Count
Odds Ratio
Evidence (Mean Rank Score)
Provenance
response to mercaptopurine
0
7.7
85.5
thiopurine methyltransferase activity measurement
0
7.7
85.5
0
1.1
77
0
5.6
21.5
age at onset
0
5.6
21.5
Orthologs (12)
1 – 5 of 12
Species
Name
Source ID
Gene ID
OMA
EggNOG
Inparanoid
Chimp
thiopurine S-methyltransferase
VGNC:7936
471863
Macaque
thiopurine S-methyltransferase
704564
Mouse
MGI:98812
22017
Dog
thiopurine S-methyltransferase
VGNC:47745
403536
Horse
thiopurine S-methyltransferase
VGNC:24436
100034066
Species
Name
OMA
EggNOG
Inparanoid
Chimp
thiopurine S-methyltransferase
Macaque
thiopurine S-methyltransferase
Mouse
Dog
thiopurine S-methyltransferase
Horse
thiopurine S-methyltransferase
Protein Structure (2 Structures, 1 AlphaFold Model)
RepresentationColor Scheme

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P51580-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 2 of 2
PDB Structure Id
Ligand
Method
Resolution (Å)
Residues
Fraction of Total Protein
Pub Year
Title
PDB Structure Id
Fraction of Total Protein
Resolution
Pub Year
Pathways (48)
Biological oxidations (R-HSA-211859)

Click on a row in the table to change the structure displayed.

Items per page:
1 – 5 of 8
Data Source
Name
Explore in Pharos
Explore in Source
Reactome
Biological oxidations
Reactome
Defective TPMT causes Thiopurine S-methyltransferase deficiency (TPMT deficiency)
Reactome
Disease
Reactome
Diseases of metabolism
Reactome
Metabolic disorders of biological oxidation enzymes
Name
Explore in Pharos
Explore in Source
Biological oxidations
Defective TPMT causes Thiopurine S-methyltransferase deficiency (TPMT deficiency)
Disease
Diseases of metabolism
Metabolic disorders of biological oxidation enzymes
Protein-Protein Interactions (61)
1 – 10 of 61
ITPA
Tbio
Family:  Enzyme
Novelty:  0.00235169
Score:  0.977
Data Source:  STRINGDB
HPRT1
Tchem
Family:  Enzyme
Novelty:  0.00032232
Score:  0.961
Data Source:  STRINGDB
IMPDH1
Tclin
Family:  Enzyme
Novelty:  0.00758575
Score:  0.94
Data Source:  STRINGDB
GMPS
Tbio
Family:  Enzyme
Novelty:  0.00611806
Score:  0.94
Data Source:  STRINGDB
IMPDH2
Tclin
Family:  Enzyme
Novelty:  0.00815361
Score:  0.934
Data Source:  STRINGDB
XDH
Tclin
Family:  Enzyme
Novelty:  0.00054185
Score:  0.933
Data Source:  STRINGDB
GGH
Tchem
Family:  Enzyme
Novelty:  0.00258239
Score:  0.902
Data Source:  STRINGDB
SLC19A1
Tchem
Family:  Transporter
Novelty:  0.00536763
Score:  0.901
Data Source:  STRINGDB
NUDT15
Tbio
Family:  Enzyme
Novelty:  0.008497
Score:  0.8
Data Source:  STRINGDB
CD82
Tbio
Novelty:  0.00146542
Score:  0.737
Data Source:  STRINGDB
Publication Statistics
PubMed Score  406.12

PubMed score by year
PubTator Score  827.59

PubTator score by year
Amino Acid Sequence
Residue Counts
Protein Sequence
ProtVista Viewer
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