{"entity":{"id":"dnmt3a","kind":"target","name":"DNA methyltransferase 3A (DNMT3A)","aka":[],"tldr":"DNMT3A writes new methyl marks on DNA; it is one of the most commonly mutated genes in acute myeloid leukaemia and is trapped by the hypomethylating drugs azacitidine and decitabine.","summary":"DNA methyltransferase 3A establishes new (de novo) cytosine methylation. Loss-of-function mutations, most often at R882, are among the commonest events in acute myeloid leukaemia and in age-related clonal haematopoiesis. Azacitidine and decitabine are incorporated into DNA and covalently trap DNA methyltransferases, including DNMT3A, leading to their degradation and to demethylation.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/DNMT3A","links":[{"label":"UniProt Q9Y6K1: DNMT3A","url":"https://www.uniprot.org/uniprotkb/Q9Y6K1/entry"},{"label":"HGNC:2978 DNMT3A","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2978"},{"label":"ChEMBL target CHEMBL1992","url":"https://www.ebi.ac.uk/chembl/explore/target/CHEMBL1992"},{"label":"Sakata-Yanagimoto et al., Nat Genet 2014: somatic RHOA G17V in angioimmunoblastic T-cell lymphoma","url":"https://doi.org/10.1038/ng.2872"},{"label":"Palomero et al., Nat Genet 2014: recurrent mutations in epigenetic regulators, RHOA and FYN in peripheral T-cell lymphoma","url":"https://doi.org/10.1038/ng.2873"}],"tags":[],"related":["dnmt1"],"cancers":["aml","mds","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["azacitidine","decitabine"],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","clonal-haematopoiesis"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma, RHOA G17V and the epigenetic mutations of T-follicular-helper lymphoma: A single substitution, G17V, in the small GTPase RHOA produces a protein that does not bind GTP and that blocks the wild-type protein as well. It is specific to the tumour cell, whereas the TET2 mutations that accompany it are found in non-tumour haematopoietic cells too, which places the TET2 lesion earlier, in the stem cell, and makes this lymphoma a disease that grows out of clonal haematopoiesis. Frequency: RHOA G17V in 68% of angioimmunoblastic T-cell lymphoma samples, with every G17V case also carrying a TET2 mutation (Sakata-Yanagimoto 2014); independently, in 22 of 35 angioimmunoblastic cases, 67%, and 8 of 44 peripheral T-cell lymphoma not otherwise specified, 18%, alongside recurrent TET2, DNMT3A and IDH2 mutations and less frequent FYN, ATM, B2M and CD58 lesions (Palomero 2014). What it changes about treatment: Not through an approved test. The hypomethylating agents are used in this disease on the strength of the TET2 and DNMT3A biology rather than on a mutation result, and azacitidine-containing regimens have shown activity in T-follicular-helper histology specifically."],"symbol":"DNMT3A","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA 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 DNMT3A: RNA low tissue specificity; high antibody staining in 37 normal tissues; highest cancer staining head and neck cancer (4 of 4 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Leukaemia, Myeloid neoplasms); Open Targets associates it with 7 specific cancer types at or above 0.5 (acute myeloid leukemia, myelodysplastic syndrome, myeloid leukemia, chronic myelomonocytic leukemia, ebv-positive nodal t- and nk-cell lymphoma, myelodysplastic syndrome with excess blasts and more). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas DNMT3A tissue","url":"https://www.proteinatlas.org/ENSG00000119772-DNMT3A/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000119772 associations","url":"https://platform.opentargets.org/target/ENSG00000119772/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:2978","ensembl":"ENSG00000119772","uniprot":"Q9Y6K1","entrez":"1788","firstDescribed":1999,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Xie et al, Gene, 1999, \"Cloning, expression and chromosome locations of the human DNMT3 gene family\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/10433969/","biology":"A de novo methyltransferase working with DNMT3L during development and in haematopoietic stem cells; the R882H mutant acts dominantly to reduce methylation.","whereFound":["Haematopoietic stem cells","Mutated in a large share of AML and in clonal haematopoiesis"],"targetClass":"enzyme","prevalence":[{"cancerId":"aml","pct":22.1,"measure":"DNMT3A mutation, exon sequencing of 281 de novo AML cases (62 mutated)","source":"https://doi.org/10.1056/NEJMoa1005143","note":"33.7% in intermediate-risk cytogenetics and absent in favourable-risk disease; R882 the commonest site"}]},"route":"/targets/dnmt3a/","neighbours":{"target":[{"id":"dnmt1","kind":"target","name":"DNMT1 (DNA methyltransferase 1)","route":"/targets/dnmt1/"},{"id":"tet2","kind":"target","name":"TET2","route":"/targets/tet2/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"mds","kind":"cancer","name":"Myelodysplastic syndromes / neoplasms (MDS)","route":"/cancers/mds/"},{"id":"angioimmunoblastic-t-cell-lymphoma","kind":"cancer","name":"Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)","route":"/cancers/angioimmunoblastic-t-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"}],"drug":[{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"},{"id":"decitabine","kind":"drug","name":"Decitabine","route":"/drugs/decitabine/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"}],"biomarker":[{"id":"rhoa-g17v","kind":"biomarker","name":"RHOA G17V","route":"/biomarkers/rhoa-g17v/"}]}}