CREBBP
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Acetylates histones, giving a specific tag for transcriptional activation. Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively).
- 3 · How drugs use it
No product in this corpus aims at CREBBP yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:2348 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q92793 (protein name, function text, keywords and locations (REST API)); CIViC gene CREBBP (5 evidence items, 0 assertions, 4 variants; diseases: Lung Non-small Cell Carcinoma, Acute Lymphoblastic Leukaemia, Diffuse Large B-cell Lymphoma, Follicular Lymphoma, Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000005339 (association with cancer (MONDO_0004992) 0.83; per-cancer scores at or above 0.5: colorectal cancer 0.57, oesophageal cancer 0.54, urinary bladder cancer 0.66, ovarian cancer 0.53, melanoma 0.55, neuroendocrine neoplasm 0.60 (GraphQL API, CC0)); IntOGen CREBBP (driver in 42 cohorts (Act 12, LoF 29); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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
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: 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.
Latest papers
topQuery for this target: (TITLE:"CREBBP" OR ABSTRACT:"CREBBP" OR TITLE:"CREB binding lysine acetyltransferase" OR ABSTRACT:"CREB binding lysine acetyltransferase" OR TITLE:"CREB-binding protein" OR ABSTRACT:"CREB-binding protein" OR TITLE:"KAT3A" OR ABSTRACT:"KAT3A") 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 CREBBP, not a curated reading list.
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