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FLASH GENE
Symbol TPMT contributors: mct/npt - updated : 21-12-2021
HGNC name thiopurine S-methyltransferase
HGNC id 12014
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 3184 - 245 - 1996 8561894
8 - 3231 - 230 - 1996 8561894
10 - 3655 - 245 - 1996 8561894
EXPRESSION
Type widely
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
 salivary gland   highly
Endocrinethyroid   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer monomer
HOMOLOGY
Homologene
FAMILY
  • methyltransferase superfamily
  • TPMT family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a by product
  • catalyses the inactivation of mercaptopurine (MP) which is widely used in the treatment of acute lymphoblastic leukaemia (ALL) of childhood (Schmiegelow 2009)
  • metabolizes thiopurine medications, including azathioprine and 6-mercaptopurine
  • is required for detoxification, through S-methylation, of 6-thioguanine nucleotides (TGNs), a byproduct of thiopurine metabolism
  • both TPMT and ABCC4 influence mercaptopurine disposition and toxicity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
    cell & other
    REGULATION
    inhibited by s-adenosyl-l-homocysteine (SAH)
    ASSOCIATED DISORDERS
    corresponding disease(s) MCPS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    low activity in mutant have an increased risk of developing thiopurine-induced myelosuppression, compared with individuals with normal activity
    Susceptibility
  • to cisplatin-induced hearing loss in children
  • to reduced enzyme activity
  • to variation of tolerance to thiopurine drugs
  • Variant & Polymorphism SNP
  • several variants with either normal or deficient TPMT activity
  • variant rs12201199, associated to cisplatin-induced hearing loss in children ((Ross 2009)
  • 25 SNP have been reported in the TPMT gene, 23 of these are associated with reduced enzyme activity (Tamm 2008)
  • TPMT polymorphisms are major determinants of tolerance to thiopurine drugs used in leukemias and nonmalignant immunologic disorders
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS