Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

TPMT

contributors: mct/npt - updated : 21-12-2021

HGNC name	thiopurine S-methyltransferase
HGNC id	12014

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000367 9 - 3184 NP_000358 - 245 - 1996 8561894 NM_001346818 8 - 3231 NP_001333747 - 230 - 1996 8561894 NM_001346817 10 - 3655 NP_001333746 - 245 - 1996 8561894

EXPRESSION

Type

widely

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly   salivary gland       highly Endocrine thyroid       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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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