# DOT1L

Source: https://onco.cc/targets/dot1l/  
OnCo record `dot1l` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

IntOGen calls it a driver in 2 cohorts (0 activating, 2 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Neuroblastoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: DOT1 like histone lysine methyltransferase; Histone-lysine N-methyltransferase, H3 lysine-79 specific; KIAA1814; DOT1; KMT4
- Tags: cancer-genes-wave
- Symbol: DOT1L
- Class: tumor-suppressor
- 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).
- Where found: Diffuse large B-cell lymphoma: IntOGen driver in 1 cohort (DLBCLNOS); Neuroblastoma: IntOGen driver in 1 cohort (NBL)

## 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.

## Sources

- HGNC HGNC:24948: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24948
- UniProt Q8TEK3: https://www.uniprot.org/uniprotkb/Q8TEK3/entry
- NCBI Gene 84444: https://www.ncbi.nlm.nih.gov/gene/84444
- Ensembl ENSG00000104885: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000104885

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Neuroblastoma (paediatric)](https://onco.cc/cancers/neuroblastoma/)
- pathways: [Menin / KMT2A (HOXA9-MEIS1 axis)](https://onco.cc/pathways/menin-kmt2a/)

---
JSON: https://onco.cc/api/v1/entities/dot1l.json