Protein / target

Catenin beta-1

Encoded byCTNNB1P35222Homo sapiensSwiss-Prot

UniProt: P35222 Ensembl: ENSG00000168036 HGNC: HGNC:2514 NCBI Gene: 1499

Clinical-stage

Therapeutic maturity

Clinical candidates

Small-molecule tractable

Druggability

Structure with Ligand

Research papers

Protein at a glance

Biological role

DNA-binding transcription factor binding

Strongest disease association

Carcinoma, Hepatocellular

Via encoding gene CTNNB1 · Genetic evidence · score 0.85

Therapeutic position

Clinically advancing target

Research activity

Emerging research

12 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Key downstream component of the canonical Wnt signaling pathway.

View complete UniProt function annotation

Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). 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 (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). 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 (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Also acts as a coactivator for other transcription factors, such as NR5A2 (PubMed:22187462). Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes (PubMed:29910125). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (By similarity). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (By similarity)

Subcellular location

CytoplasmNucleusCytoplasm, cytoskeletonCell junction, adherens junctionCell junctionCell membraneCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, spindle poleSynapseCytoplasm, cytoskeleton, cilium basal body

Domains and Gene Ontology detail (138)

Gene Ontology

Cadherens junction
Capical part of cell
Capicolateral plasma membrane
Cbasolateral plasma membrane
Cbeta-catenin destruction complex
Cbeta-catenin-TCF complex
Cbeta-catenin-TCF7L2 complex
Cbicellular tight junction
Ccatenin complex
Ccell cortex
Ccell junction
Ccell periphery

781 aa · 85 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingUniProt · GOCell proliferation & survivalGOGrowth-factor signallingGOCell-cycle regulationGOCell adhesionUniProt · GOTranscriptional regulationUniProt · GO

View supporting evidence

Synaptic signalling

·Synapse
·glutamatergic synapse
·postsynaptic density, intracellular component
·postsynaptic membrane

Cell proliferation & survival

·negative regulation of cell population proliferation
·positive regulation of cell population proliferation

Growth-factor signalling

·epidermal growth factor receptor signaling pathway

Cell-cycle regulation

·negative regulation of mitotic cell cycle, embryonic

Cell adhesion

·Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed…
·Cell junction, adherens junction
·Cell junction
·bicellular tight junction

Transcriptional regulation

·Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed…
·transcription regulator complex
·DNA-binding transcription factor binding
·RNA polymerase II-specific DNA-binding transcription factor binding

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CTNNB1

Gene-level evidence surfaced through the gene CTNNB1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Carcinoma, Hepatocellular

0.96Well supported

Genetic evidence dominant · Open Targets 0.78

Medulloblastoma

0.91Well supported

Genetic evidence dominant · Open Targets 0.73

Ovarian Neoplasms

0.89Well supported

Genetic evidence dominant · Open Targets 0.62

Colorectal Neoplasms

0.85Well supported

Genetic evidence dominant · Open Targets 0.62

Prostate adenocarcinoma

0.48Limited support

Somatic mutation evidence dominant · Open Targets 0.55

View evidence synthesis (5)

Carcinoma, HepatocellularWell supported

0.96

agreement 0.87–1.00

Genetic45%Somatic mutation30%Animal model9%Pathway8%Literature8%

Open Targets aggregate 0.78 · 5 independent evidence families

MedulloblastomaWell supported

0.91

agreement 0.81–1.00

Genetic44%Somatic mutation32%Animal model16%Literature7%Genetic literaturedup

Open Targets aggregate 0.73 · 4 independent evidence families · 1 not counted as duplicate

Ovarian NeoplasmsWell supported

0.89

agreement 0.79–0.99

Genetic59%Somatic mutation26%Animal model10%Literature4%Genetic literaturedup

Open Targets aggregate 0.62 · 4 independent evidence families · 1 not counted as duplicate

Colorectal NeoplasmsWell supported

0.85

agreement 0.76–0.95

Genetic67%Animal model19%Clinical8%Literature6%Genetic literaturedup

Open Targets aggregate 0.62 · 4 independent evidence families · 1 not counted as duplicate

Prostate adenocarcinomaLimited support

0.48

agreement 0.32–0.64

Somatic mutation96%Literature4%

Open Targets aggregate 0.55 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Carcinoma, Hepatocellular0.78

Medulloblastoma0.73

Colorectal Neoplasms0.62

Ovarian Neoplasms0.62

Prostate adenocarcinoma0.55

Listeriosis0.55

Drug development

1 compounds recorded · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (1)

PRI-724Phase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (11)

SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · Human Protein Atlas locPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

response to thalidomideClinPGxresponse to cyclophosphamide, dexamethasone, and thalidomideClinPGxneutropeniaClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.