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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CTNNA3
catenin alpha 3
Chromosome 10 · 10q21.3
NCBI Gene: 29119Ensembl: ENSG00000183230.18HGNC: HGNC:2511UniProt: A8K141
79PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingbeta-catenin bindingbundle of His cell-Purkinje myocyte adhesion involved in cell communicationregulation of heart rate by cardiac conductionArrhythmogenic right ventricular dysplasiaatrial fibrillationfamilial isolated arrhythmogenic right ventricular dysplasiaAbruptio Placentae
✦AI Summary

CTNNA3 (catenin alpha 3) encodes α-T-catenin, a critical component of the cardiomyocyte intercalated disc that mediates stretch-resistant cell-cell adhesion 1. The protein functions as a bridge between cadherin-based adhesion complexes and the actin cytoskeleton, providing mechanical linkage essential for cardiac tissue integrity 2. CTNNA3 is predominantly expressed in cardiomyocytes and regulates cardiac conduction and action potential duration 3. Phosphorylation of CTNNA3 at specific residues is crucial for maintaining its localization at the intercalated disc and regulating cell-cell conductance 1. Fortilin protects CTNNA3 from phosphorylation-induced ubiquitination and proteasomal degradation, thereby suppressing apoptosis 4. Beyond cardiac function, CTNNA3 acts as a tumor suppressor in hepatocellular carcinoma by inhibiting proliferation and invasion through Akt signal suppression 5. Clinically, CTNNA3 is implicated in arrhythmogenic disorders: rare structural variants (deletions) associate with atrial fibrillation risk 3, and phosphorylation abnormalities contribute to dilated cardiomyopathy pathophysiology 1. Copy number variations in CTNNA3 are also associated with pediatric food allergy susceptibility 6. These findings establish CTNNA3 as a multifunctional protein with critical roles in cardiac homeostasis and cellular protection mechanisms.

Sources cited
1
CTNNA3 phosphorylation at intercalated disc maintains protein localization and regulates conductance in dilated cardiomyopathy
PMID: 37126683
2
CTNNA3 deletions associate with atrial fibrillation risk in genome-wide sequencing study
PMID: 40050430
3
Alpha T-catenin provides link between cadherin-based adhesion complex and cytoskeleton for cell-cell adhesion
PMID: 12596047
4
Fortilin protects CTNNA3 against phosphorylation, ubiquitination, and proteasomal degradation to prevent apoptosis
PMID: 39747445
5
CTNNA3 functions as tumor suppressor in hepatocellular carcinoma by inhibiting proliferation and invasion
PMID: 26882563
6
CTNNA3 copy number variations associate with pediatric food allergy susceptibility
PMID: 26188062
Disease Associationsⓘ21
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.62Moderate
atrial fibrillationOpen Targets
0.49Moderate
familial isolated arrhythmogenic right ventricular dysplasiaOpen Targets
0.48Moderate
Abruptio PlacentaeOpen Targets
0.44Moderate
atrial flutterOpen Targets
0.40Weak
placenta praeviaOpen Targets
0.38Weak
male reproductive organ cancerOpen Targets
0.38Weak
familial isolated arrhythmogenic ventricular dysplasia, biventricular formOpen Targets
0.37Weak
familial isolated arrhythmogenic ventricular dysplasia, left dominant formOpen Targets
0.37Weak
familial isolated arrhythmogenic ventricular dysplasia, right dominant formOpen Targets
0.37Weak
preeclampsiaOpen Targets
0.35Weak
liver diseaseOpen Targets
0.34Weak
arrhythmogenic right ventricular cardiomyopathyOpen Targets
0.34Weak
frozen shoulderOpen Targets
0.33Weak
smoking initiationOpen Targets
0.31Weak
kidney diseaseOpen Targets
0.31Weak
Prolonged QT intervalOpen Targets
0.31Weak
ovarian neoplasmOpen Targets
0.29Weak
heart failureOpen Targets
0.28Weak
brain injuryOpen Targets
0.28Weak
Arrhythmogenic right ventricular dysplasia, familial, 13UniProt
Pathogenic Variants5
NM_013266.4(CTNNA3):c.160del (p.Arg54fs)Likely pathogenic
Long QT syndrome
★☆☆☆2024→ Residue 54
NM_013266.4(CTNNA3):c.2159+2T>CLikely pathogenic
Arrhythmogenic right ventricular dysplasia 13
★☆☆☆2023
NM_013266.4(CTNNA3):c.2293TTG[1] (p.Leu766del)Pathogenic
Arrhythmogenic right ventricular dysplasia 13|Arrhythmogenic right ventricular cardiomyopathy
☆☆☆☆2017→ Residue 766
NM_013266.4(CTNNA3):c.281T>A (p.Val94Asp)Pathogenic
Arrhythmogenic right ventricular dysplasia 13
☆☆☆☆2013→ Residue 94
NM_013266.4(CTNNA3):c.2568del (p.Lys856fs)Likely pathogenic
Malignant tumor of urinary bladder
☆☆☆☆→ Residue 856
View on ClinVar ↗
Related Genes
ACTG1Protein interaction99%ACTBProtein interaction98%ACTN4Protein interaction97%ACTN1Protein interaction97%CDH1Protein interaction97%CDH2Protein interaction97%
Tissue Expression6 tissues
Heart
100%
Brain
14%
Liver
2%
Ovary
1%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CTNNA3ACTG1ACTBACTN4ACTN1CDH1CDH2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q8WW10
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.88LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.70 [0.56–0.88]
RankingsWhere CTNNA3 stands among ~20K protein-coding genes
  • #5,986of 20,598
    Most Researched79
  • #3,540of 5,498
    Most Pathogenic Variants5
  • #7,744of 17,882
    Most Constrained (LOEUF)0.88
Genes detectedCTNNA3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Proteomics and phosphoproteomics of failing human left ventricle identifies dilated cardiomyopathy-associated phosphorylation of CTNNA3.
PMID: 37126683
Proc Natl Acad Sci U S A · 2023
1.00
2
Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk.
PMID: 40050430
Nat Genet · 2025
0.90
3
Expression of ovine CTNNA3 and CAP2 genes and their association with growth traits.
PMID: 34481004
Gene · 2022
0.80
4
Assessment of the CTNNA3 gene encoding human alpha T-catenin regarding its involvement in dilated cardiomyopathy.
PMID: 12596047
Hum Genet · 2003
0.70
5
Fortilin binds CTNNA3 and protects it against phosphorylation, ubiquitination, and proteasomal degradation to guard cells against apoptosis.
PMID: 39747445
Commun Biol · 2025
0.60