CTNNB1
CTNNB1 (Catenin beta-1) 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 an approved or late-stage drug is recorded against it. Tied to Hepatocellular carcinoma, Colorectal cancer, Ovarian cancer and 5 more.
Overview
Key downstream component of the canonical Wnt signalling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes.
CIViC holds 43 clinical evidence items and 1 assertion across 16 variants, naming Meloxicam, Imatinib, Anti-CTLA-4 Monoclonal Antibody and Anti-PD-L1 Monoclonal Antibody and others. Open Targets scores its association with cancer at 0.89 (direct and indirect evidence; datatypes clinical 0.16, genetic literature 0.72, affected pathway 0.85, literature 0.99, genetic association 0.82, somatic mutation 0.97, animal model 0.68). IntOGen calls it a driver in 47 cohorts (46 activating, 1 loss-of-function), covering Adrenocortical Carcinoma, Colon Adenocarcinoma, Colorectal Adenocarcinoma, Oesophageal Adenocarcinoma, Hepatocellular Carcinoma, Hepatoblastoma and others. In OnCo, 1 product record names it (Nirogacestat).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · CTNNB1 (Catenin beta-1) 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 an approved or late-stage drug is recorded against it. Tied to Hepatocellular carcinoma, Colorectal cancer, Ovarian cancer and 5 more.
- 1 · What it is
CTNNB1 (Catenin beta-1) 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 an approved or late-stage drug is recorded against it. Tied to Hepatocellular carcinoma, Colorectal cancer, Ovarian cancer and 5 more.
- 2 · What goes wrong in cancer
Key downstream component of the canonical Wnt signalling pathway.
- 3 · How drugs use it
No product in this corpus aims at CTNNB1 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:2514 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P35222 (protein name, function text, keywords and locations (REST API)); CIViC gene CTNNB1 (43 evidence items, 1 assertions, 16 variants; diseases: Desmoid Tumour, Hepatoblastoma, Childhood Medulloblastoma, Pancreatic Solid Pseudopapillary Carcinoma, Adamantinous Craniopharyngioma and 5 more (GraphQL API, CC0)); Open Targets ENSG00000168036 (association with cancer (MONDO_0004992) 0.89; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.68, colorectal cancer 0.72, hepatocellular carcinoma 0.80, prostate cancer 0.59, urinary bladder cancer 0.58, renal cell carcinoma 0.61 (GraphQL API, CC0)); IntOGen CTNNB1 (driver in 47 cohorts (Act 46, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Key downstream component of the canonical Wnt signalling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Also acts as a coactivator for other transcription factors, such as NR5A2. Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes. Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex. Location: Cytoplasm; Nucleus; Cytoplasm, cytoskeleton; Cell junction, adherens junction (UniProt). Locus 3p22.1 (HGNC).
- Hepatocellular carcinoma: Open Targets association 0.80 with hepatocellular carcinoma (MONDO_0007256); IntOGen driver in 9 cohorts (HCC)
- Colorectal cancer: Open Targets association 0.72 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease
- Ovarian cancer: Open Targets association 0.70 with ovarian cancer (MONDO_0008170); IntOGen driver in 1 cohort (OVT)
- Lung cancer: Open Targets association 0.69 with lung cancer (MONDO_0008903)
- Endometrial cancer: Open Targets association 0.67 with endometrial cancer (MONDO_0011962); IntOGen driver in 4 cohorts (UCEC)
- Prostate cancer: Open Targets association 0.59 with prostate cancer (MONDO_0008315); IntOGen driver in 7 cohorts (PRAD, PROSTATE)
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 46 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 43 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Childhood Medulloblastoma; Pancreatic Solid Pseudopapillary Carcinoma; Adamantinous Craniopharyngioma; Medulloblastoma WNT Activated; Salivary Gland Basal Cell Adenoma.
Latest papers
topQuery for this target: (TITLE:"CTNNB1" OR ABSTRACT:"CTNNB1" OR TITLE:"catenin beta 1" OR ABSTRACT:"catenin beta 1" OR TITLE:"Catenin beta-1" OR ABSTRACT:"Catenin beta-1" OR TITLE:"beta-catenin" OR ABSTRACT:"beta-catenin" OR TITLE:"armadillo" OR ABSTRACT:"armadillo" OR TITLE:"CTNNB" OR ABSTRACT:"CTNNB") 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 CTNNB1, not a curated reading list.
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