{"entity":{"id":"mgmt-protein","kind":"target","name":"MGMT (O6-methylguanine-DNA methyltransferase)","aka":["O-6-methylguanine-DNA methyltransferase","AGT","O6-alkylguanine DNA alkyltransferase"],"tldr":"MGMT is a DNA repair enzyme that removes the damage temozolomide causes; when the gene is switched off by methylation the tumour cannot repair itself and the drug works better.","summary":"MGMT is a suicide enzyme that transfers alkyl groups off the O6 position of guanine onto itself, reversing the lesion that temozolomide and nitrosoureas rely on. Promoter methylation silences the gene in about 40 percent of glioblastomas and predicts longer survival with temozolomide; the readout page under this target carries the test methods and the trials that use methylation to select or spare chemotherapy.","asOf":"2026-09-23","wikipedia":"https://en.wikipedia.org/wiki/O-6-methylguanine-DNA_methyltransferase","links":[{"label":"HGNC HGNC:7059","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7059"},{"label":"UniProt P16455","url":"https://www.uniprot.org/uniprotkb/P16455/entry"}],"tags":["biomarker-parent"],"related":["mgmt-promoter-methylation"],"cancers":["glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":["temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":["mgmt"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"MGMT","role":["drug-target","biomarker","dna-repair"],"evidenceTier":"approved-drug","sources":[],"specificity":"tumour-associated","distribution":"one-type","specificityNote":"Tumour-associated overexpression: HPA finds the RNA tissue enhanced in normal liver, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA MGMT: RNA tissue enhanced (liver 126 nTPM); high antibody staining in 30 normal tissues; highest cancer staining renal cancer (6 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Brain and spinal cord tumours (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas MGMT tissue","url":"https://www.proteinatlas.org/ENSG00000170430-MGMT/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas MGMT pathology","url":"https://www.proteinatlas.org/ENSG00000170430-MGMT/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000170430 associations","url":"https://platform.opentargets.org/target/ENSG00000170430/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7059","ensembl":"ENSG00000170430","uniprot":"P16455","entrez":"4255","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Tano et al, Proc. Natl. Acad. Sci. U.S.A, 1990, \"Isolation and structural characterization of a cDNA clone encoding the human DNA repair protein for O6-alkylguanine\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2405387/","biology":"Loss of MGMT leaves O6-methylguanine unrepaired, which mispairs with thymine and triggers mismatch-repair-driven cell death; tumours that lose mismatch repair as well become hypermutated and resistant.","whereFound":["Glioblastoma (promoter methylation in about 40 percent)","Lower-grade gliomas","Neuroendocrine tumours (low MGMT expression and alkylator response)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/mgmt-protein/","neighbours":{"biomarker":[{"id":"mgmt-promoter-methylation","kind":"biomarker","name":"MGMT promoter methylation","route":"/biomarkers/mgmt-promoter-methylation/"}],"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"drug":[{"id":"temozolomide","kind":"drug","name":"Temozolomide","route":"/drugs/temozolomide/"}],"term":[{"id":"mgmt","kind":"term","name":"MGMT promoter methylation","route":"/terms/mgmt/"}],"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"}]}}