Protocadherin gamma subfamily A, 9 (PCDHGA9)

Protocadherin gamma subfamily A, 9 (PCDHGA9) is a member of the clustered protocadherin gamma family, belonging to the cadherin superfamily of cell adhesion receptors. It consists of an extracellular region with six cadherin domains, a transmembrane domain, and a cytoplasmic region shared with other gamma protocadherins. PCDHGA9 is implicated in the establishment and maintenance of specific cell-cell connections, especially in the brain and vascular endothelium. In endothelial cells, PCDHGA9 acts as a suppressor of the anti-inflammatory transcription factors Klf2/4 via Notch pathway interaction and cleavage-dependent nuclear signaling, promoting pro-inflammatory activation and atherosclerosis under disturbed flow conditions. Inhibition of PCDHGA9, such as with function-blocking antibodies, relieves suppression of Klf2/4, decreases vascular inflammation, and reduces atherosclerotic lesion formation in animal models, identifying PCDHGA9 as a potential therapeutic target in inflammatory vascular disease. The gene is also associated with certain neurodevelopmental disorders.

Other names

Protocadherin gamma-A9PCDHGA9PCDH-gamma-A9PCDH-GAMMA-A9protocadherin gamma-A9

Inhibition of PCDHGA9, particularly via blocking antibody, relieves suppression of anti-inflammatory Klf2/4, increasing endothelial resilience and protecting against atherosclerosis. Antibody-mediated blocking of cell-adhesion disrupts PCDHGA9-mediated pro-inflammatory signaling.