DOT1L
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.
Overview
Histone methyltransferase that methylates 'Lys-79' of histone H3. Histones in nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
IntOGen calls it a driver in 2 cohorts (0 activating, 2 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Neuroblastoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Histone methyltransferase that methylates 'Lys-79' of histone H3. Histones in nucleosomes are preferred as substrate compared to free histones.
- 3 · How drugs use it
No product in this corpus aims at DOT1L yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:24948 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q8TEK3 (protein name, function text, keywords and locations (REST API)); IntOGen DOT1L (driver in 2 cohorts (Act 0, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- Diffuse large B-cell lymphoma: IntOGen driver in 1 cohort (DLBCLNOS)
- Neuroblastoma: IntOGen driver in 1 cohort (NBL)
Notes
top- 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.
Latest papers
topQuery for this target: (TITLE:"DOT1L" OR ABSTRACT:"DOT1L" OR TITLE:"DOT1 like histone lysine methyltransferase" OR ABSTRACT:"DOT1 like histone lysine methyltransferase" OR TITLE:"Histone-lysine N-methyltransferase, H3 lysine-79 specific" OR ABSTRACT:"Histone-lysine N-methyltransferase, H3 lysine-79 specific" OR TITLE:"KIAA1814" OR ABSTRACT:"KIAA1814" OR TITLE:"DOT1" OR ABSTRACT:"DOT1" OR TITLE:"KMT4" OR ABSTRACT:"KMT4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about DOT1L, not a curated reading list.
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