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FLASH GENE
Symbol TPMT contributors: mct/npt - updated : 05-03-2010
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
EC.number 2.1.1.67
DNA
TYPE functioning gene
STRUCTURE 26.83 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
LOC346113 6p22.3 similar to ARP2/3 complex 21 kDa subunit (p21-ARC) (Actin-related protein 2/3 complex subunit 3) LOC391871 6 similar to malate dehydrogenase 1; malate dehydrogenase, soluble; Malate dehydrogenase-like enzyme MYLIP 6p23-p22.3 myosin regulatory light chain interacting protein MRPL42P2 6p22.3 myosin regulatory light chain interacting protein GMPR 6p23 guanosine monophosphate reductase SCA1 6p23 spinocerebellar ataxia 1 (olivopontocerebellar ataxia 1, autosomal dominant, ataxin 1) RNPC6 6p22.3 RNA-binding region (RNP1, RRM) containing 6 CAP2 6p22.3 CAP, adenylate cyclase-associated protein, 2 (yeast) FAM8A1 6p23 family with sequence similarity 8, member A1 NUP153 6p25.3-p22.1 nucleoporin 153kDa KIF13A 6p23 kinesin family member 13A NHLRC1 6p22.3 NHL repeat containing 1 TPMT 6p22.3 thiopurine S-methyltransferase AOF1 6p22.3 amine oxidase, flavin containing 1 DEK 6p23 DEK oncogene (DNA binding) LOC391872 6 similar to ATP-dependent RNA helicase DDX18 (DEAD-box protein 18) (Myc-regulated DEAD-box protein) (MrDb) LOC391873 6 similar to inosine monophosphate dehydrogenase 1 isoform b; sWSS2608 IBRDC2 6p22.3 IBR domain containing 2 LOC346129 6p22.3 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) ID4 6p23-p22.3 inhibitor of DNA binding 4, dominant negative helix-loop-helix protein LOC391874 6 similar to 60S ribosomal protein L29 (Cell surface heparin binding protein HIP) OACT1 6p22.3 O-acyltransferase (membrane bound) domain containing 1
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 3258 - 245 - Szumlanski (1996)
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
  • catalyzing the s-methylation of thiopurine drugs such as 6-mercaptopurine
  • 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)
    • 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
    Susceptibility
  • to cisplatin-induced hearing loss in children
  • to reduced enzyme activity
    • 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)
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS