{{Rsnum
|rsid=1142345
|Gene=TPMT
|Chromosome=6
|position=18130687
|Orientation=plus
|GMAF=0.04591
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=TPMT
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 94.7 | 5.3 | 0.0
| HCB | 98.5 | 1.5 | 0.0
| JPT | 94.7 | 5.3 | 0.0
| YRI | 91.8 | 8.2 | 0.0
| ASW | 84.2 | 15.8 | 0.0
| CHB | 98.5 | 1.5 | 0.0
| CHD | 94.5 | 5.5 | 0.0
| GIH | 95.0 | 5.0 | 0.0
| LWK | 78.9 | 19.3 | 1.8
| MEX | 86.2 | 10.3 | 3.4
| MKK | 95.5 | 4.5 | 0.0
| TSI | 97.1 | 2.9 | 0.0
| HapMapRevision=28
}}{{CPMC SNP
|link=https://cpmc.coriell.org/Sections/Results/TPMT.aspx?pgId=221
}}[[rs1142345]] is a SNP in the [[TPMT]] gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning [[TPMT]] alleles for the toxicity to be pronounced.

The risk allele for this SNP is [[rs1142345]](G), and when it is the only variant in the TPMT gene, it encodes the TPMT*3C allele. While still rare, it is more common in African-Americans (2.4% of all alleles) than in Caucasians. Note that if the same allele also carries the [[rs1800460]](A) SNP, the allele is actually a TPMT*3A allele [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=187680&a=187680_AllelicVariant0002 (OMIM)].

The medicine [[6-Mercaptopurine]] is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment. 

[http://blog.23andme.com/2009/11/10/snpwatch-genetic-variations-may-impact-risk-of-hearing-loss-in-children-receiving-common-chemotherapy-drug/ 23andMe blog] hearing loss linked to a chemotherapy drug named [[Cisplatin]].

[[http://en.wikipedia.org/wiki/Thiopurine_methyltransferase| wikipedia]] thiopurine drugs metabolized by TPMT include [[azathioprine]], [[mercaptopurine]], and [[thioguanine]]

{{PharmGKB
|RSID=rs1142345
|Name_s=TPMT*3C
|Gene_s=NHLRC1, TPMT
|Feature=Intron, Exon/NonSyn
|Evidence=PubMed ID:15228163
|Annotation=Carriers of this variant have low, no, or intermediate (in the case of heterozygotes) TPMT activity, putting them at risk for hematologic toxicity if treated with thiopurines.
|Drugs=azathioprine; mercaptopurine
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA162263516
}}

{{PharmGKB
|RSID=rs1142345
|Name_s=TPMT*3C
|Gene_s=NHLRC1, TPMT
|Feature=Intron, Exon/NonSyn
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/tpmt/variant.jsp
|Annotation=Decreased activity and increased degradation in vitro
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145152
}}

{{omim
|id=187680
|rsnum=1142345
|variant=0002
}}

{{omim
|id=187680
|rsnum=1142345
|variant=0005
}}

{{ClinVar
|rsid=1142345
|Reversed=1
|FwdREF=A
|FwdALT=G
|REF=T
|ALT=C
|RSPOS=18130918
|CHROM=6
|GMAF=0.0462
|dbSNPBuildID=86
|SSR=0
|SAO=1
|VP=0x050378000000150517110100
|GENEINFO=TPMT:7172
|GENE_NAME=TPMT
|GENE_ID=7172
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000006.11:g.18130918T>C
|CLNSRC=GTR; OMIM Allelic Variant
|CLNORIGIN=1
|CLNSRCID=GTR000500004; 187680.0002; 187680.0005
|CLNSIG=5
|CLNCUI=C0342801; C0342801
|CLNDBN=Thiopurine methyltransferase deficiency
|Disease=Thiopurine methyltransferase deficiency
|CLNACC=RCV000013559.22; RCV000013562.22
|Tags=RV;PM;TPA;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.9541; 0.04591
|CLNDSDB=MedGen:OMIM:SNOMED_CT
|CLNDSDBID=C0342801:610460:238012003
|COMMON=1
}}

{{PMID Auto
|PMID=18547414
|Title=Genotyping panel for assessing response to cancer chemotherapy.
|OA=1
}}

{{PMID Auto
|PMID=18662289
|Title=Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.
|OA=1
}}

{{PMID Auto
|PMID=18685564
|Title=Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia.
|OA=1
}}

{{GET Evidence
|gene=TPMT
|aa_change=Tyr240Cys
|aa_change_short=Y240C
|impact=pharmacogenetic
|qualified_impact=Low clinical importance,  pharmacogenetic
|inheritance=other
|quality_scores=Array
|dbsnp_id=rs1142345
|overall_frequency_n=496
|overall_frequency_d=10740
|overall_frequency=0.0461825
|n_genomes=7
|n_genomes_annotated=0
|n_haplomes=8
|n_articles=4
|n_articles_annotated=4
|qualityscore_in_silico=3
|qualitycomment_in_silico=Y
|qualityscore_case_control=5
|qualitycomment_case_control=Y
|qualityscore_familial=0
|qualityscore_severity=3
|qualitycomment_severity=Y
|qualityscore_treatability=5
|qualitycomment_treatability=Y
|in_omim=Y
|in_pharmgkb=Y
|pph2_score=1.0
|nblosum100=6
|autoscore=4
|webscore=N
|variant_evidence=0
|clinical_importance=2
|summary_short=Alone, this variant is known as TPMT*3C -- but often, especially in Caucasians, it is found together with another nonsynonymous variant (A154T) to produce the TPMT*3A variant. Both variants are associated with loss of thiopurine methyltransferase (TPMT) activity, although *3C is milder than *3A. Inability to metabolize thiopurine drugs can lead to severe adverse reactions. Heterozygotes may be advised to take a reduced dosage due to reduced metabolism of the drug.
}}

{{PMID Auto
|PMID=23133420
|Title=Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.
|OA=1
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}