CTNNA1

CTNNA1 is a protein-coding gene in humans that encodes alpha-1 catenin, a cytoplasmic component of adherens junctions. Alpha-1 catenin belongs to the alpha-catenin family and functions as a linker between cadherin-based cell–cell adhesion complexes and the actin cytoskeleton. The protein interacts with beta-catenin and the cytoplasmic tail of classical cadherins, most notably E-cadherin (CDH1), facilitating junction assembly, stabilization, and the transmission of mechanical signals that influence cell shape and tissue architecture.

In cells, CTNNA1 contributes to the organization and maintenance of epithelial adherens junctions, regulates actin dynamics, and supports proper cell polarity. Its activity is important for tissue integrity during development and for maintaining epithelial barriers in mature tissues. Disruption of CTNNA1 can weaken intercellular adhesion and alter cell motility, with potential effects on development and disease.

Clinical significance: Germline variants in CTNNA1 have been associated with hereditary diffuse gastric cancer (HDGC), often in families with or without CDH1 mutations. CTNNA1 alterations may also be found in sporadic cancers and are studied for their potential role in tumor progression and metastasis through loss of cell adhesion. The penetrance and full spectrum of disease risk associated with CTNNA1 variants are under investigation, and genetic testing for CTNNA1 is considered in HDGC risk assessment in some guidelines.

Interactions: CTNNA1 interacts with E-cadherin (CDH1), beta-catenin (CTNNB1), and other components of the cadherin–catenin–actin complex, linking cell adhesion to the actin cytoskeleton.