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FLASH GENE
Symbol TPMT contributors: mct/npt - updated : 21-12-2021
HGNC name thiopurine S-methyltransferase
HGNC id 12014
Corresponding disease
MCPS six-mercaptopurine sensitivity
Location 6p22.3      Physical location : 18.128.545 - 18.155.374
Synonym name S-adenosyl-L-methionine:thiopurine S-methyltransferase
Synonym symbol(s) TPMTD
EC.number 2.1.1.67
DNA
TYPE functioning gene
STRUCTURE 26.86 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • a variable number of GC-rich tandem repeats (VNTRs), namely A, B and C, ranging from three to nine repeats in length in an A(n)B(m)C architecture
  • SP1 and SP3 transcription factors bind to the VNTR repeats
  • MAPPING cloned Y linked N status provisional
    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