# EP300

Source: https://onco.cc/targets/ep300/  
OnCo record `ep300` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

EP300 (Histone acetyltransferase p300) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Bladder & urothelial cancer, Head and neck squamous cell carcinoma and 5 more.

## Summary

Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation.

CIViC holds 2 clinical evidence items and 0 assertions across 2 variants. Open Targets scores its association with cancer at 0.87 (direct and indirect evidence; datatypes affected pathway 0.82, literature 0.99, genetic association 0.69, somatic mutation 0.95, animal model 0.59). IntOGen calls it a driver in 30 cohorts (10 activating, 20 loss-of-function), covering Angiosarcoma, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Cervical Squamous Cell Carcinoma, Cholangiocarcinoma, Colorectal Adenocarcinoma and others.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: EP300 lysine acetyltransferase; Histone acetyltransferase p300; p300; KAT3B
- Tags: cancer-genes-wave
- Symbol: EP300
- Class: transcription
- Biology: Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localises at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively). Also able to acetylate histone lysine residues that are already monomethylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation. Location: Cytoplasm; Nucleus; Chromosome (UniProt). Locus 22q13.2 (HGNC).
- Where found: Colorectal cancer: Open Targets association 0.74 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COADREAD); Bladder & urothelial cancer: Open Targets association 0.65 with urinary bladder cancer (MONDO_0001187); IntOGen driver in 7 cohorts (BLCA, UTUC); Head and neck squamous cell carcinoma: Open Targets association 0.62 with head and neck squamous cell carcinoma (MONDO_0010150); IntOGen driver in 3 cohorts (HNSC); Non-Hodgkin lymphoma: Open Targets association 0.62 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL); Lung cancer: Open Targets association 0.62 with lung cancer (MONDO_0008903); Cervical cancer: Open Targets association 0.60 with cervical cancer (MONDO_0002974); IntOGen driver in 3 cohorts (CESC)

## 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 an activating (Act) driver in 10 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 20 cohorts; CIViC holds 2 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Lymphoma, BCL6 and the germinal-centre programme: BCL6 is the master transcriptional repressor of the germinal centre: it switches off the DNA-damage response and the differentiation programme so that a B cell can tolerate deliberate mutation of its own immunoglobulin genes. A lymphoma that keeps BCL6 on keeps a cell in a state where mutation is permitted and apoptosis is suppressed. The protein is normally switched off by acetylation, which is one reason CREBBP and EP300 loss matters here. Frequency: BCL6 rearrangement in 28.7% of 442 diffuse large B-cell lymphomas, the commonest of the three translocations (Horn 2013); BCL6 fusions with NOTCH2 mutations define the BN2 subtype (Schmitz 2018). What it changes about treatment: Nothing yet. There is no approved BCL6 inhibitor or degrader, and the group's prognosis in the genetic classification is comparatively favourable, which is a reason to study de-escalation rather than a reason to change treatment now.
- Lymphoma, CREBBP, EP300 and the rest of the chromatin machinery: CREBBP and EP300 are acetyltransferases. Losing one allele lowers the dose of acetylation, which leaves BCL6 acetylated less often and therefore active more often, and leaves p53 acetylated less often and therefore working less well; the same lesion also turns down the enhancers that would let a germinal-centre cell present antigen to T cells. KMT2D, formerly MLL2, writes H3K4 monomethylation at enhancers and is the single most frequently mutated gene in follicular lymphoma. Frequency: Genomic deletion or somatic mutation removing or inactivating the acetyltransferase domain of CREBBP or, more rarely, EP300 in about 39% of diffuse large B-cell lymphoma and 41% of follicular lymphoma, usually on one allele only (Pasqualucci 2011). KMT2D mutated in 32% of diffuse large B-cell lymphoma and 89% of follicular lymphoma in the discovery series, with MEF2B in 11.4% and 13.4% (Morin 2011); the coding genome of diffuse large B-cell lymphoma carries more than 30 clonally represented alterations per case (Pasqualucci 2011, Nat Genet). What it changes about treatment: Not yet. The pairing of CREBBP loss with HDAC3 dependency is the clearest synthetic-lethal hypothesis in B-cell lymphoma and is in trials; no approval depends on a CREBBP result.

## Sources

- HGNC HGNC:3373: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3373
- UniProt Q09472: https://www.uniprot.org/uniprotkb/Q09472/entry
- NCBI Gene 2033: https://www.ncbi.nlm.nih.gov/gene/2033
- Ensembl ENSG00000100393: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000100393
- Horn et al., Blood 2013: MYC, BCL2 and BCL6 rearrangement and expression in 442 RICOVER patients: https://doi.org/10.1182/blood-2012-06-435842
- Schmitz et al., N Engl J Med 2018: genetics and pathogenesis of diffuse large B-cell lymphoma (574 biopsies; MCD, BN2, N1, EZB): https://doi.org/10.1056/NEJMoa1801445
- Pasqualucci et al., Nature 2011: inactivating mutations of the acetyltransferase genes CREBBP and EP300 in B-cell lymphoma: https://doi.org/10.1038/nature09730
- Morin et al., Nature 2011: frequent mutation of histone-modifying genes in non-Hodgkin lymphoma: https://doi.org/10.1038/nature10351
- Pasqualucci et al., Nat Genet 2011: the coding genome of diffuse large B-cell lymphoma: https://doi.org/10.1038/ng.892

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Cervical cancer](https://onco.cc/cancers/cervical/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/)
- pathways: [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Prostate cancer (KEGG map)](https://onco.cc/pathways/prostate-cancer-signalling/), [The germinal centre reaction](https://onco.cc/pathways/germinal-centre-reaction/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- key papers: [Comprehensive genomic profiles of small cell lung cancer](https://onco.cc/key-papers/paper-george-sclc-genomic-profiles-nature-2015/), [Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas](https://onco.cc/key-papers/paper-campbell-pan-lung-somatic-alterations-nat-genet-2016/)
- terms: [FLIPI, FLIPI2 and POD24 (follicular lymphoma risk)](https://onco.cc/terms/flipi/), [The germinal centre: why lymphoma starts where antibodies are made](https://onco.cc/terms/lymphoma-bio-germinal-centre/)

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JSON: https://onco.cc/api/v1/entities/ep300.json