{"entity":{"id":"gart","kind":"target","name":"GART (trifunctional purine synthesis enzyme)","aka":[],"tldr":"GART is one of the enzymes that builds purines from scratch; pemetrexed blocks it alongside thymidylate synthase, which is why the drug starves fast-growing lung and mesothelioma cells.","summary":"The trifunctional protein GART carries three activities of de novo purine synthesis, including glycinamide ribonucleotide formyltransferase, a folate-dependent step. Pemetrexed, once polyglutamated inside cells, inhibits thymidylate synthase most strongly but also GART and dihydrofolate reductase, giving it a multi-targeted antifolate action in non-small cell lung cancer and mesothelioma.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Trifunctional_purine_biosynthetic_protein_adenosine-3","links":[{"label":"UniProt P22102: GART","url":"https://www.uniprot.org/uniprotkb/P22102/entry"},{"label":"HGNC:4163 GART","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4163"},{"label":"ChEMBL target CHEMBL3972","url":"https://www.ebi.ac.uk/chembl/explore/target/CHEMBL3972"}],"tags":[],"related":["tyms","dhfr"],"cancers":["nsclc","mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":["pemetrexed"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"GART","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA lists GART among essential proteins and finds the RNA at low tissue specificity; the 1 medicine aimed at it (Pemetrexed) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA GART: RNA low tissue specificity; no normal tissue stained high; highest cancer staining testis cancer (10 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Mesothelioma); Open Targets associates it with 3 specific cancer types at or above 0.5 (non-small cell lung carcinoma, mesothelioma, malignant pleural mesothelioma). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas GART tissue","url":"https://www.proteinatlas.org/ENSG00000159131-GART/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000159131 associations","url":"https://platform.opentargets.org/target/ENSG00000159131/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:4163","ensembl":"ENSG00000159131","uniprot":"P22102","entrez":"2618","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Aimi et al, Nucleic Acids Res, 1990, \"De novo purine nucleotide biosynthesis: cloning of human and avian cDNAs encoding the trifunctional glycinamide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase by functional complementation in E. coli\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2147474/","biology":"A cytosolic enzyme of the purine pathway whose activity rises with proliferation; inhibition depletes purine nucleotides needed for DNA and RNA.","whereFound":["Proliferating cells generally","Lung adenocarcinoma and mesothelioma treated with pemetrexed"],"targetClass":"enzyme","prevalence":[{"cancerId":"metastatic-cancer","pct":"all","measure":"Housekeeping enzyme present in every dividing cell (purine synthesis); not a selection marker, which is why these drugs are given by cancer type rather than by test."}]},"route":"/targets/gart/","neighbours":{"target":[{"id":"dhfr","kind":"target","name":"Dihydrofolate reductase (DHFR)","route":"/targets/dhfr/"},{"id":"impdh2","kind":"target","name":"IMP dehydrogenase (IMPDH2)","route":"/targets/impdh2/"},{"id":"tyms","kind":"target","name":"Thymidylate synthase (TYMS)","route":"/targets/tyms/"}],"cancer":[{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"pemetrexed","kind":"drug","name":"Pemetrexed","route":"/drugs/pemetrexed/"}]}}