Protocadherin-12 (PCDH12)

Protocadherin-12 (PCDH12) is a cell adhesion molecule belonging to the protocadherin gene family, a subfamily of the cadherin superfamily[1][3]. It is characterized by an extracellular domain with 6 cadherin repeats, a transmembrane domain, and a distinctive cytoplasmic tail that does not bind catenins like classical cadherins[1][3]. It is expressed primarily at interendothelial junctions and is involved in promoting calcium-dependent cellular aggregation and adhesion, with weak interaction to the cytoskeleton[3]. PCDH12 plays a crucial role in early brain development, particularly in maintaining neural progenitor pools, regulating neurogenesis, and ensuring proper neuronal migration through regulation of actin cytoskeleton dynamics and interaction with the WAVE regulatory complex (WRC)[2]. Loss-of-function variants in PCDH12 are associated with severe neurodevelopmental disorders characterized by premature neuronal differentiation, disrupted laminar organization, corpus callosum agenesis, and epilepsy[2]. The protein can be cleaved by ADAM10, releasing its ectodomain, which is detectable in body fluids[2]. There are currently no approved drugs targeting PCDH12, and its cell-adhesion and developmental functions raise potential safety concerns for therapeutic interventions interfering with its activity.

Other names

Protocadherin-12PCDH12VE-cad-2VE-cadherin-2Vascular cadherin-2Vascular endothelial cadherin-2DMJDS1VECAD2

Not established for any approved drugs - Inhibitors of ADAM10 (e.g., GI254023X), which block the proteolytic cleavage of PCDH12, can modulate its function in preclinical models[2]