{"entity":{"id":"dnmt1","kind":"target","name":"DNMT1 (DNA methyltransferase 1)","aka":[],"tldr":"The enzyme that copies methylation marks onto newly made DNA, keeping genes silenced. Azacitidine and decitabine trap and destroy it, waking silenced tumour suppressor genes in blood cancers.","summary":"DNMT1 maintains DNA methylation by copying the pattern from the parent strand to the new strand after replication. Azacitidine and decitabine are cytidine analogues incorporated into DNA that covalently trap DNMT1, which is then degraded, so methylation is lost over successive cell divisions and silenced genes are re-expressed; at higher doses they are also directly cytotoxic. They are standard treatment for higher-risk myelodysplastic syndromes and, with venetoclax, for older or unfit patients with acute myeloid leukaemia. Oral decitabine with cedazuridine matches intravenous exposure.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/DNMT1","links":[{"label":"UniProt P26358: DNMT1","url":"https://www.uniprot.org/uniprotkb/P26358/entry"}],"tags":[],"related":[],"cancers":["mds","aml","cmml"],"sections":[],"technologies":[],"targets":[],"drugs":["azacitidine","decitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"DNMT1","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA lists DNMT1 among essential proteins and finds the RNA at low tissue specificity; the 2 medicines aimed at it (Azacitidine, Decitabine) 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 DNMT1: RNA low tissue specificity; high antibody staining in 5 normal tissues; highest cancer staining lymphoma (1 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Myeloid neoplasms, Leukaemia); Open Targets associates it with 4 specific cancer types at or above 0.5 (acute myeloid leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, myelodysplastic syndrome with excess blasts). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas DNMT1 tissue","url":"https://www.proteinatlas.org/ENSG00000130816-DNMT1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000130816 associations","url":"https://platform.opentargets.org/target/ENSG00000130816/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:2976","ensembl":"ENSG00000130816","uniprot":"P26358","entrez":"1786","firstDescribed":1992,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Yen R.-W.C. et al, Nucleic Acids Res, 1992, \"Isolation and characterization of the cDNA encoding human DNA methyltransferase\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1594447/","biology":"Maintenance DNA methyltransferase acting at hemimethylated CpG sites after replication; covalently trapped by incorporated azacytosine.","whereFound":["Myelodysplastic syndromes","Acute myeloid leukaemia","Chronic myelomonocytic leukaemia"],"targetClass":"enzyme","prevalence":[{"cancerId":"metastatic-cancer","pct":"all","measure":"Housekeeping enzyme present in every dividing cell (methylation maintenance during replication); not a selection marker, which is why these drugs are given by cancer type rather than by test."}]},"route":"/targets/dnmt1/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"cmml","kind":"cancer","name":"Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms","route":"/cancers/cmml/"},{"id":"mds","kind":"cancer","name":"Myelodysplastic syndromes / neoplasms (MDS)","route":"/cancers/mds/"}],"drug":[{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"},{"id":"decitabine","kind":"drug","name":"Decitabine","route":"/drugs/decitabine/"}],"target":[{"id":"dnmt3a","kind":"target","name":"DNA methyltransferase 3A (DNMT3A)","route":"/targets/dnmt3a/"}]}}