CTNNB1

Chr 3AD

catenin beta 1

Also known as: CTNNB, EVR7, MRD19, NEDSDV, armadillo

NCBI Gene: 1499 ENSG00000168036 UniProt: P35222 OMIM: 116806

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Colorectal cancer, somaticMIM #114500

Exudative vitreoretinopathy 7MIM #617572

Hepatocellular carcinoma, somaticMIM #114550

Medulloblastoma, somaticMIM #155255

Neurodevelopmental disorder with spastic diplegia and visual defectsMIM #615075

Ovarian cancer, somaticMIM #167000

Pilomatricoma, somaticMIM #132600

UniProtPilomatrixoma

UniProtMesothelioma, malignant

UniProtVitreoretinopathy, exudative 7

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · CTNNB1-related neurodevelopmental disorder and/or vitreoretinopathy · AD · ClinGen 2024
Definitive · severe intellectual disability-progressive spastic diplegia syndrome · AD · G2P
Definitive · exudative vitreoretinopathy · AD · G2P
Strong · exudative vitreoretinopathy 7 · AD · Labcorp Genetics (formerly Invitae)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

884

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.13

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — CTNNB1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.13LOEUF

pLI 1.000

Z-score 5.46

OE 0.03 (0.01–0.13)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.85Z-score

OE missense 0.47 (0.42–0.53)

199 obs / 421.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.13)

0≤0.351.4

Missense OE?0.47 (0.42–0.53)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 1 / 36.7Missense obs/exp: 199 / 421.1Syn Z: 0.14

Background carrier burden — how many people carry a rare variant somewhere in CTNNB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

595 rare PASS variants

Rare truncating (LoF)

1 in 8,700

28 rare PASS variants

Rare synonymous (reference)

1 in 98

346 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CTNNB1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 15,000
South Asian	~43k	1 in 150	1 in 3,900
Remaining (unassigned)	~30k	1 in 250	≈ 1 in 30,000
European (Finnish)	~27k	1 in 640	≈ 1 in 13,000
Admixed American	~22k	1 in 210	1 in 1,700
African / African American	~21k	1 in 200	none seen
East Asian	~20k	1 in 250	1 in 3,300
Ashkenazi Jewish	~13k	1 in 1,000	none seen
Middle Eastern	~2,884	1 in 360	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — CTNNB1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

CTNNB1 Neurodevelopmental Syndrome

CTNNB1 Neurodevelopmental Syndrome - Natural History Study

RECRUITING

NCT07167732University Medical Centre LjubljanaStarted 2024-06-14

A General Medical and Neurological AssessmentWorld Health Organisation (WHO) Motor MilestonesBurke-Fahn-Marsden Dystonia Rating Scale

Lung Cancer

Feasibility of Targeted Bronchial Washing for Molecular Testing by Next Generation Sequencing in Early-stage Lung Cancer

ACTIVE NOT RECRUITING

NCT06301295Phase NAPusan National University HospitalStarted 2024-05-29

Ultarthin bronchoscopy with intratumoral washing

16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING

NCT01238250Simons SearchlightStarted 2010-10

Colorectal Cancer

ASPirin Intervention for the REDuction of Colorectal Cancer Risk

ACTIVE NOT RECRUITING

NCT02394769Phase NAMassachusetts General HospitalStarted 2015-07-06

AspirinPlacebo for Aspirin

CTNNB1L-DOPA

Study of L-dopa Treatment in Patients With a Neurodevelopmental Disorder (CTNNB1 Gene)

RECRUITING

NCT07614126Phase NAUniversity Hospital, MontpellierStarted 2026-04-08

L-Dopa

Unresectable Colorectal Neoplasm Metastasis

Study of a Tankyrase Inhibitor RK-582 for Patients With Unresectable Metastatic Colorectal Cancer

RECRUITING

NCT06853496Phase PHASE1Eiji ShinozakiStarted 2025-03-13

RK-582

Advanced Hepatocellular CarcinomaMetastatic Hepatocellular Carcinoma

A Study to Evaluate ALN-BCAT in Patients With Hepatocellular Carcinoma

RECRUITING

NCT06600321Phase PHASE1Alnylam PharmaceuticalsStarted 2024-12-30

ALN-BCATPembrolizumab

Advanced Hepatocellular CarcinomaMetastatic Hepatocellular CarcinomaStage III Hepatocellular Carcinoma AJCC v8

Testing 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

RECRUITING

NCT06811116Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2025-11-17

Biospecimen CollectionCabozantinib S-malateImaging Procedure

CTNNB1 Neurodevelopmental Syndrome

Gene Replacement Therapy for Treatment of Paediatric Patients With CTNNB1 Neurodevelopmental Syndrome

RECRUITING

NCT07270549Phase PHASE1, PHASE2CTNNB1 FoundationStarted 2025-11-01

Urbagen gene addition therapySirolimusMethylprednisolone (Corticosteroid)

Metastatic Colorectal Carcinoma (mCRC)Colorectal Cancer (CRC)Adenomatous Polyposis Coli (APC) Gene Mutation

Safety and Efficacy of Tegavivint in Patients With Metastatic Colorectal Carcinoma

RECRUITING

NCT07463599Phase PHASE1, PHASE2HonorHealth Research InstituteStarted 2026-02-17