CTNNB1
Chr 3ADcatenin beta 1
Also known as: CTNNB, EVR7, MRD19, NEDSDV, armadillo
This protein functions in cell adhesion by constituting adherens junctions necessary for epithelial cell layer formation, anchoring the actin cytoskeleton, and transmitting contact inhibition signals to regulate cell division. Autosomal dominant loss-of-function mutations cause a neurodevelopmental disorder with spastic diplegia and visual defects, as well as exudative vitreoretinopathy. The protein is extremely intolerant to loss-of-function variants, with somatic mutations also associated with various cancers including medulloblastoma.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CTNNB1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
ASPirin Intervention for the REDuction of Colorectal Cancer Risk
ACTIVE NOT RECRUITINGFeasibility of Targeted Bronchial Washing for Molecular Testing by Next Generation Sequencing in Early-stage Lung Cancer
ACTIVE NOT RECRUITINGOnline Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGProspective Pilot Study Identifying Clinically Relevant Biological Targets for Medical Therapy
ENROLLING BY INVITATIONTesting the Addition of an Anti-cancer Drug, Sapanisertib, to the Usual Chemotherapy Treatment (Cabozantinib) in Metastatic Liver Cell Cancer With a Change in Genes for the Protein β-Catenin, The SAPHIRE Trial
RECRUITINGCTNNB1 Neurodevelopmental Syndrome - Natural History Study
RECRUITINGPreliminary Experimental Study on Key Technologies for Early Screening of Gastric Cancer
RECRUITINGBuilding Resilience at Schools: Emotional and Biological Assessment and Treatment of Traumatic Stress
RECRUITINGStudy of a Tankyrase Inhibitor RK-582 for Patients With Unresectable Metastatic Colorectal Cancer
RECRUITINGSafety and Efficacy of Tegavivint in Patients With Metastatic Colorectal Carcinoma
RECRUITINGA Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery
ACTIVE NOT RECRUITINGA Study to Evaluate ALN-BCAT in Patients With Hepatocellular Carcinoma
RECRUITINGExternal Resources
Links to major genomics databases and tools