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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.
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).
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.
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.
Key downstream component of the canonical Wnt signalling pathway.
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.
Tumour-specific alteration: 1 of 1 medicines aimed at it name a mutant, fusion, exon or hotspot in their mechanism (Nirogacestat), an alteration absent from normal cells. HPA CTNNB1: RNA low tissue specificity; high antibody staining in 33 normal tissues; highest cancer staining colorectal cancer (12 of 12 high). Distribution: 9 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Biliary tract cancer (all types), Hepatocellular carcinoma, Colorectal cancer, Ovarian cancer, Lung cancer (all types), Endometrial cancer, Prostate cancer and more); Open Targets associates it with 10 specific cancer types at or above 0.5 (pilomatrixoma, hepatocellular carcinoma, medulloblastoma, ovarian cancer, colorectal cancer, hepatoblastoma and more). (Rule 4 of scripts/fetch-target-specificity.ts.)
Sources: FDA label (DailyMed); Human Protein Atlas CTNNB1 tissue; Open Targets ENSG00000168036 associations
First described 1994. Earliest sequence paper UniProt cites for the protein: Huelsken et al, J. Cell Biol, 1994, "E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton". Source.
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)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Cerebral cortex, Lung, Soft tissue.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 5-7% | Activating mutation or large in-frame deletion | cBioPortal: 503 of 7,237, 7.0%, in crc_msk_2026; 84 of 1,134, 7.4%, in crc_msk_2017; 106 of 1,516, 7.0%, in crc_eo_2020; 33 of 534, 6.2%, in coadread_tcga_pan_can_atlas_2018; 36 of 619, 5.8%, in coadread_dfci_2016. Structural variants disrupt CTNNB1 in 29 of 7,237 crc_msk_2026 samples. Large in-frame CTNNB1 deletions, missed by standard variant calling, were part of what took WNT alteration to 96% of tumours (Yaeger 2018). | cBioPortal (TCGA) |
| Gallbladder cancer | 6% | Mutation (Wnt activation) | Mutation in 15 of 244 samples, 6.1%, in cBioPortal gbc_mskcc_2022 and 6 of 103, 5.8%, in gbc_msk_2018; a significantly mutated gene not previously linked to gallbladder cancer, with recurrent Wnt pathway alterations (Pandey 2020); a critical event in co-existing adenoma, high-grade BilIN and carcinoma lesions (Lin 2021). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Molecular confirmation that the visible precursor is not always the parent of the cancer beside it, which tempers hopes that finding and removing dysplasia catches every tumour, and puts Wnt signalling through CTNNB1 at the start of the raised route.
A three-continent cohort from high-incidence countries, and the origin of the idea that a shared frameshift (ELF3) could be a vaccine target in a cancer with few targets. CTNNB1 and STK11 from this list recur in the MSK data.
It is the caution attached to the sidedness rule: a tumour at the hepatic flexure and one at the caecum are both called right-sided and are not the same disease.
It turned sidedness from an epidemiological curiosity into a mechanistic statement, and it is the reason a wild-type mitogenic report on a left-sided tumour is read as ligand dependence rather than as an absence.
It gives a genetic account of both immunotherapy failures: why some mismatch repair deficient tumours resist, and why the microsatellite-stable majority has no T cells in it to begin with.
It is the reference multi-platform dataset and the reason a KRAS wild-type report is treated as a search for another driver rather than as an absence.
The evidence that molecular cyst-fluid testing can spare operations, now part of specialist practice although not a universal standard.
It put RNF43 on the pancreatic driver list and gave cyst fluid testing a way to separate the harmless serous cyst from the mucinous ones that need watching.
Query 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.
Shares Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways, A combination of molecular markers and clinical features improve the classification of pancreatic cysts, Clinical sequencing defines the genomic landscape of metastatic colorectal cancer, Integrated genomic characterization of pancreatic ductal adenocarcinoma.
Shares Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate, Hepatocellular carcinoma (KEGG map), Endometrial cancer, Renal cell carcinoma.
Shares Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate, Genetic mechanisms of immune evasion in colorectal cancer, Nirogacestat, Clinical sequencing defines the genomic landscape of metastatic colorectal cancer.
Shares Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes, A combination of molecular markers and clinical features improve the classification of pancreatic cysts, Integrated genomic characterization of pancreatic ductal adenocarcinoma, Hepatocellular carcinoma.
Shares Adrenocortical carcinoma, Renal cell carcinoma, CIViC, IntOGen.
Shares Hepatocellular carcinoma (KEGG map), CIViC, IntOGen, Ovarian cancer.
Shares Integrated genomic characterization of pancreatic ductal adenocarcinoma, Endometrial cancer, Gallbladder cancer, Hepatocellular carcinoma.
Shares Intracholecystic papillary-tubular neoplasm (ICPN), Metaplasia, dysplasia, carcinoma in situ: the flat route to gallbladder cancer, Gallbladder cancer.