Have questions? Visit https://www.reddit.com/r/SNPedia

rs1800460

From SNPedia

Orientationminus
Stabilizedminus
Geno Mag Summary
(A;A) 3.5 incapable of detoxifying byproducts of certain drugs
(A;G) 3 (TPMT*3B) impaired drug metabolism
(G;G) 0 normal
ReferenceGRCh38 38.1/142
Chromosome6
Position18138997
GeneTPMT
is asnp
is mentioned by
dbSNPrs1800460
ebirs1800460
HLIrs1800460
Exacrs1800460
Varsomers1800460
Maprs1800460
PheGenIrs1800460
hapmaprs1800460
1000 genomesrs1800460
hgdprs1800460
ensemblrs1800460
gopubmedrs1800460
geneviewrs1800460
scholarrs1800460
googlers1800460
pharmgkbrs1800460
gwascentralrs1800460
openSNPrs1800460
23andMers1800460
23andMe allrs1800460
SNP Nexus

SNPshotrs1800460
SNPdbers1800460
MSV3drs1800460
GWAS Ctlgrs1800460
GMAF0.01699
Max Magnitude3.5
CPMC Logo.png

This SNP has been recognized by the Coriell Personalized Medicine Collaborative ICOB.
Additional information is available here

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 (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.

[Wikipedia] thiopurine drugs metabolized by TPMT include azathioprine, mercaptopurine, and thioguanine


OMIM187680
Desc
Variant0002
Relatedalso
OMIM187680
Desc
Variant0004
Relatedalso


ClinVar
Risk rs1800460(A;A)
Alt rs1800460(A;A)
Reference rs1800460(G;G)
Significance Drug-response
Disease Thiopurine methyltransferase deficiency
Variation info
Gene TPMT
CLNDBN Thiopurine methyltransferase deficiency
Reversed 1
HGVS NC_000006.11:g.18139228C>T
CLNSRC OMIM Allelic Variant
CLNACC RCV000013559.24, RCV000013561.18,



[PMID 17366837OA-icon.png] Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada.


[PMID 18547414OA-icon.png] Genotyping panel for assessing response to cancer chemotherapy.


[PMID 18662289OA-icon.png] Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.


[PMID 18685564OA-icon.png] Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia.


[PMID 22385887] High prevalence of polymorphism and low activity of thiopurine methyltransferase in patients with inflammatory bowel disease.


GET Evidence
TPMT-A154T
aa_change Ala154Thr
aa_change_short A154T
impact pharmacogenetic
qualified_impact Low clinical importance, Likely pharmacogenetic
overall_frequency 0.0280774
summary 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 23133420OA-icon.png] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.