ArticleScientific reports2017
One amino acid makes a difference-Characterization of a new TPMT allele and the influence of SAM on TPMT stability.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Structural and Functional Disruption of Thiopurine S‑Methyltransferase by the A80P Variant: A Simulation and Genotyping Study.ACS omega · 2026Article
- Higher prevalence ofFrontiers in pharmacology · 2025Article
- Pharmacogenetic Effect of Thiopurine Methyl Transferase (TPMT) Gene Expression and Serum TNF on the Imuran Response in Ulcerative Colitis (UC) Iraqi Patients.Reports of biochemistry & molecular biology · 2023Article
- Population-Specific Distribution ofTherapeutics and clinical risk management · 2023Article
- A bioinformatics approach to the identification of novel deleterious mutations of human TPMT through validated screening and molecular dynamics.Scientific reports · 2022Article
- Article
- Optimizing thiopurine therapy in children with acute lymphoblastic leukemia: A promising "MINT" sequencing strategy and therapeutic "DNA-TG" monitoring.Frontiers in pharmacology · 2022Review
- Thiopurine pharmacogenomics and pregnancy in inflammatory bowel disease.Journal of gastroenterology · 2021Review
- No association between relapse hazard and thiopurine methyltransferase geno- or phenotypes in non-high risk acute lymphoblastic leukemia: a NOPHO ALL2008 sub-study.Cancer chemotherapy and pharmacology · 2021Article
- Pharmacogenetic studies of thiopurine methyltransferase genotype-phenotype concordance and effect of methotrexate on thiopurine metabolism.Basic & clinical pharmacology & toxicology · 2021Review
- Review
- Comparison ofWorld journal of gastroenterology · 2018Observational
- Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping.Journal of gastroenterology · 2018Review
- In Vitro Protein Stability of Two Naturally Occurring ThiopurineACS omega · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thiopurine induced toxicity is associated with defects in the thiopurine methyltransferase (TPMT) gene. TPMT is a polymorphic enzyme, with most of the single nucleotide polymorphisms (SNPs) causing an amino acid change, altering the enzymatic activity of the TPMT protein. In this study, we characterize a novel patient allele c.719A > C, named TPMT*41, together with the more common variant *3C c.719A > G, resulting in an amino acid shift at tyrosine 240 to serine, p.Y240S and cysteine, p.Y240C respectively. We show that the patient heterozygote for c.719A > C has intermediate enzymatic activity in red blood cells. Furthermore, in vitro studies, using recombinant protein, show that TPMT p.Y240S is less stable than both TPMTwt and TPMT p.Y240C. The addition of SAM increases the stability and, in agreement with Isothermal Titration Calorimetry (ITC) data, higher molar excess of SAM is needed in order to stabilize TPMT p.Y240C and TPMT p.Y240S compared to TPMTwt. Molecular dynamics simulations show that the loss of interactions is most severe for Y240S, which agrees with the thermal stability of the mutations. In conclusion, our study shows that SAM increases the stability of TPMT and that changing only one amino acid can have a dramatic effect on TPMT stability and activity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.