{"entity":{"id":"dot1l","kind":"target","name":"DOT1L","aka":["DOT1 like histone lysine methyltransferase","Histone-lysine N-methyltransferase, H3 lysine-79 specific","KIAA1814","DOT1","KMT4"],"tldr":"DOT1L (Histone-lysine N-methyltransferase, H3 lysine-79 specific) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Diffuse large B-cell lymphoma and Neuroblastoma.","summary":"Histone methyltransferase that methylates 'Lys-79' of histone H3. Histones in nucleosomes are preferred as substrate compared to free histones. Binds to DNA.\n\nIntOGen calls it a driver in 2 cohorts (0 activating, 2 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Neuroblastoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:24948","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24948"},{"label":"UniProt Q8TEK3","url":"https://www.uniprot.org/uniprotkb/Q8TEK3/entry"},{"label":"NCBI Gene 84444","url":"https://www.ncbi.nlm.nih.gov/gene/84444"},{"label":"Ensembl ENSG00000104885","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000104885"}],"tags":["cancer-genes-wave"],"related":["intogen"],"cancers":["dlbcl","neuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["menin-kmt2a"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts. Evidence tier \"cohort-driver\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"DOT1L","role":["tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:24948","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24948","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q8TEK3","url":"https://www.uniprot.org/uniprotkb/Q8TEK3/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"IntOGen DOT1L","url":"https://www.intogen.org/search?gene=DOT1L","note":"driver in 2 cohorts (Act 0, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificitySources":[],"hgnc":"HGNC:24948","ensembl":"ENSG00000104885","uniprot":"Q8TEK3","entrez":"84444","firstDescribed":2001,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Nagase et al, DNA Res, 2001, \"Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/11347906/","biology":"Histone methyltransferase that methylates 'Lys-79' of histone H3. Histones in nucleosomes are preferred as substrate compared to free histones. Binds to DNA. Together with MLLT3/AF9, is involved in SCNN1A transcriptional repression following H3K79 hypermethylation at the promoter. Location: Nucleus; Cytoplasm (UniProt). Locus 19p13.3 (HGNC).","whereFound":["Diffuse large B-cell lymphoma: IntOGen driver in 1 cohort (DLBCLNOS)","Neuroblastoma: IntOGen driver in 1 cohort (NBL)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/dot1l/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"neuroblastoma","kind":"cancer","name":"Neuroblastoma (paediatric)","route":"/cancers/neuroblastoma/"}],"pathway":[{"id":"menin-kmt2a","kind":"pathway","name":"Menin / KMT2A (HOXA9-MEIS1 axis)","route":"/pathways/menin-kmt2a/"}]}}