{{Rsnum
|rsid=1800460
|Gene=TPMT
|Chromosome=6
|position=18138997
|Orientation=plus
|GMAF=0.01699
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=TPMT
}}{{CPMC SNP
|link=https://cpmc.coriell.org/Sections/Results/TPMT.aspx?pgId=221
}}[[rs1800460]] 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 [[rs1800460]](A), and when it is the only variation in the TPMT gene, it encodes the TPMT*3B allele. While still rare, it is more common in Caucasians (4.5% of all alleles) than in African-Americans (0.8%). Note that if the same allele also carries the [[rs1142345]](G) 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://en.wikipedia.org/wiki/Thiopurine_methyltransferase Wikipedia]] thiopurine drugs metabolized by TPMT include [[azathioprine]], [[mercaptopurine]], and [[thioguanine]]

{{PharmGKB
|RSID=rs1800460
|Name_s=TPMT*3B
|Gene_s=TPMT
|Feature=Exon/NonSyn
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/tpmt/variant.jsp
|Annotation=Decreased activity in vitro, associated with drug-related toxicities
|Drugs=
|Drug Classes=PURINE ANALOGUES
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145151
}}

{{omim
|id=187680
|rsnum=1800460
|variant=0002
}}

{{omim
|id=187680
|rsnum=1800460
|variant=0004
}}

{{ClinVar
|rsid=1800460
|Reversed=1
|FwdREF=G
|FwdALT=A
|REF=C
|ALT=T
|RSPOS=18139228
|CHROM=6
|GMAF=0.0174
|dbSNPBuildID=127
|SSR=0
|SAO=1
|VP=0x050378000000150516110100
|GENEINFO=TPMT:7172
|GENE_NAME=TPMT
|GENE_ID=7172
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000006.11:g.18139228C>T
|CLNSRC=GTR; OMIM Allelic Variant
|CLNORIGIN=1
|CLNSRCID=GTR000500004; 187680.0002; 187680.0004
|CLNSIG=5
|CLNCUI=C0342801; CN077959\x2cCN077995\x2cCN078017
|CLNDBN=Thiopurine methyltransferase deficiency
|Disease=Thiopurine methyltransferase deficiency
|CLNACC=RCV000013559.22; RCV000013561.16
|Tags=RV;PM;TPA;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPROD;OTHERKG;LSD;OM
|CAF=0.983; 0.01699
|CLNDSDB=MedGen:OMIM:SNOMED_CT
|CLNDSDBID=C0342801:610460:238012003
|COMMON=1
}}

{{PMID Auto
|PMID=17366837
|Title=Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada.
|OA=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
}}

{{PMID Auto
|PMID=22385887
|Title=High prevalence of polymorphism and low activity of thiopurine methyltransferase in patients with inflammatory bowel disease.
}}

{{GET Evidence
|gene=TPMT
|aa_change=Ala154Thr
|aa_change_short=A154T
|impact=pharmacogenetic
|qualified_impact=Low clinical importance, Likely pharmacogenetic
|inheritance=recessive
|quality_scores=Array
|dbsnp_id=rs1800460
|overall_frequency_n=302
|overall_frequency_d=10756
|overall_frequency=0.0280774
|n_genomes=3
|n_genomes_annotated=0
|n_haplomes=4
|n_articles=4
|n_articles_annotated=4
|qualityscore_in_silico=1
|qualitycomment_in_silico=Y
|qualityscore_case_control=5
|qualitycomment_case_control=Y
|qualityscore_severity=4
|qualitycomment_severity=Y
|qualityscore_treatability=5
|qualitycomment_treatability=Y
|in_omim=Y
|pph2_score=0.667
|nblosum100=1
|autoscore=3
|webscore=N
|variant_evidence=0
|clinical_importance=1
|summary_short=Usually this variant is found in combination Y240C, forming the TPMT*3A variant. When alone, this variant produces the *3B variant. Both variants are associated with loss of thiopurine methyltransferase (TPMT) activity. 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 | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}