{"entity":{"id":"tyms","kind":"target","name":"Thymidylate synthase (TYMS)","aka":[],"tldr":"The enzyme that makes the thymine building block of DNA. Fluorouracil, capecitabine and pemetrexed jam it, starving dividing cells of thymidine.","summary":"Thymidylate synthase methylates dUMP to dTMP, the only de novo source of thymidine for DNA synthesis. Fluorouracil, given directly or as the oral prodrug capecitabine, is converted to FdUMP, which forms a stable ternary complex with the enzyme and its folate cofactor; leucovorin (folinic acid) is added to stabilise that complex, which is why FOLFOX and FOLFIRI include it. Pemetrexed inhibits thymidylate synthase alongside other folate enzymes. High tumour TYMS expression is associated with fluoropyrimidine resistance, and DPD deficiency causes severe fluoropyrimidine toxicity.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Thymidylate_synthase","links":[{"label":"UniProt P04818: TYMS","url":"https://www.uniprot.org/uniprotkb/P04818/entry"}],"tags":[],"related":[],"cancers":["colorectal","gastric","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["fluorouracil","capecitabine","pemetrexed"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"TYMS","role":[],"sources":[],"specificity":"lineage-antigen","distribution":"few-types","specificityNote":"Lineage antigen shared with normal bone marrow cells and lymphoid tissue cells: HPA finds the gene tissue enhanced in bone marrow, lymphoid tissue, and the 7 medicines aimed at it (Fluorouracil (5-FU), Capecitabine, Pemetrexed and more) act on the wild-type protein, so the normal lineage is hit too. HPA TYMS: RNA tissue enhanced (bone marrow 84 nTPM, lymphoid tissue 106 nTPM); blood lineage group enriched (NK-cells 7 nTPM, T-cells 14 nTPM); high antibody staining in 4 normal tissues; highest cancer staining head and neck cancer (1 of 4 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Gastric & gastro-oesophageal junction cancer, Pancreatic ductal adenocarcinoma); approvals of single-target medicines aimed at it also list Breast cancer (all types), Hepatocellular carcinoma, Mesothelioma, not counted; Open Targets associates it with 14 specific cancer types at or above 0.5 (dyskeratosis congenita, digenic, non-small cell lung carcinoma, breast cancer, colorectal cancer, dyskeratosis congenita, breast carcinoma and more). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas TYMS tissue","url":"https://www.proteinatlas.org/ENSG00000176890-TYMS/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas TYMS pathology","url":"https://www.proteinatlas.org/ENSG00000176890-TYMS/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000176890 associations","url":"https://platform.opentargets.org/target/ENSG00000176890/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:12441","ensembl":"ENSG00000176890","uniprot":"P04818","entrez":"7298","firstDescribed":1985,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Takeishi et al, Nucleic Acids Res, 1985, \"Nucleotide sequence of a functional cDNA for human thymidylate synthase\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2987839/","biology":"Folate-dependent enzyme converting dUMP to dTMP; inhibited by FdUMP in a ternary complex with 5,10-methylenetetrahydrofolate.","whereFound":["Gastrointestinal cancers treated with fluoropyrimidines","Non-squamous lung cancer and mesothelioma treated with pemetrexed"],"targetClass":"enzyme","prevalence":[{"cancerId":"metastatic-cancer","pct":"all","measure":"Housekeeping enzyme present in every dividing cell (thymidine synthesis); not a selection marker, which is why these drugs are given by cancer type rather than by test."}]},"route":"/targets/tyms/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"doxifluridine","kind":"drug","name":"Doxifluridine","route":"/drugs/doxifluridine/"},{"id":"floxuridine","kind":"drug","name":"Floxuridine","route":"/drugs/floxuridine/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"leucovorin","kind":"drug","name":"Leucovorin (folinic acid)","route":"/drugs/leucovorin/"},{"id":"pemetrexed","kind":"drug","name":"Pemetrexed","route":"/drugs/pemetrexed/"},{"id":"raltitrexed","kind":"drug","name":"Raltitrexed","route":"/drugs/raltitrexed/"}],"target":[{"id":"gart","kind":"target","name":"GART (trifunctional purine synthesis enzyme)","route":"/targets/gart/"}]}}