# CREBBP

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

## TL;DR

CREBBP (CREB-binding protein) is a protein that switches other genes on and off. The public catalogues list it as a drug target, 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 Non-Hodgkin lymphoma, Bladder & urothelial cancer, Leukaemia and 5 more.

## Summary

Acetylates histones, giving a specific tag for transcriptional activation. Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1.

CIViC holds 5 clinical evidence items and 0 assertions across 4 variants, naming MTOR Inhibitor, C646, HDAC Inhibitor OBP-801 and Therapeutic Glucocorticoid. Open Targets scores its association with cancer at 0.83 (direct and indirect evidence; datatypes clinical 0.16, affected pathway 0.84, literature 0.99, genetic association 0.20, somatic mutation 0.97, animal model 0.58). IntOGen calls it a driver in 42 cohorts (12 activating, 29 loss-of-function), covering Acute Lymphoblastic Leukaemia, Basal Cell Carcinoma, Bladder/Urinary Tract, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Renal Clear Cell Carcinoma and others.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: CREB binding lysine acetyltransferase ; CREB-binding protein; KAT3A
- Tags: cancer-genes-wave
- Symbol: CREBBP
- Class: transcription
- Biology: Acetylates histones, giving a specific tag for transcriptional activation. Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers. Location: Cytoplasm; Nucleus (UniProt). Locus 16p13.3 (HGNC).
- Where found: Non-Hodgkin lymphoma: Open Targets association 0.74 with non-Hodgkin lymphoma (MONDO_0018908); CIViC evidence names this disease; Bladder & urothelial cancer: Open Targets association 0.66 with urinary bladder cancer (MONDO_0001187); IntOGen driver in 7 cohorts (BLADDER, BLCA, UTUC); Leukaemia: Open Targets association 0.65 with leukaemia (MONDO_0005059); Neuroendocrine tumours: Open Targets association 0.60 with neuroendocrine neoplasm (MONDO_0019496); IntOGen driver in 1 cohort (NETNOS); Oesophageal cancer: Open Targets association 0.54 with oesophageal cancer (MONDO_0007576); IntOGen driver in 2 cohorts (ESCA); Breast cancer: Open Targets association 0.51 with breast cancer (MONDO_0007254); IntOGen driver in 2 cohorts (BRCA)

## 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: Open Targets known-drug datatype score 0.16; IntOGen calls it an activating (Act) driver in 12 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 29 cohorts; CIViC holds 5 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:2348: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2348
- UniProt Q92793: https://www.uniprot.org/uniprotkb/Q92793/entry
- NCBI Gene 1387: https://www.ncbi.nlm.nih.gov/gene/1387
- Ensembl ENSG00000005339: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000005339
- 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/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [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/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [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/), [The germinal centre reaction](https://onco.cc/pathways/germinal-centre-reaction/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- terms: [Cell of origin (GCB vs ABC)](https://onco.cc/terms/cell-of-origin/), [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/)
- 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/)

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