Protocadherin gamma-C4 (PCDHGC4)

Protocadherin gamma-C4 (PCDHGC4) is a calcium-dependent neural cell adhesion molecule belonging to the cadherin superfamily, encoded by the PCDHGC4 gene in the gamma cluster on chromosome 5[1][2][4]. The protocadherin gamma cluster consists of 22 genes subdivided into three subfamilies (A, B, C), and PCDHGC4 is one of three genes in the more distantly related subfamily C[1][2]. Structurally, it is a type I transmembrane protein with six extracellular cadherin (EC) domains and a variable cytoplasmic region, followed by a constant cytoplasmic C-terminal region encoded by shared exons within the cluster[1][4]. PCDHGC4 is essential for establishment and maintenance of specific neuronal connections, and plays a unique, non-redundant role in postnatal neuronal survival, particularly for cortical inhibitory interneurons (cINs) during developmental programmed cell death[2][3]. Genetic disruption of PCDHGC4 in model organisms leads to severe neurodevelopmental phenotypes and early postnatal lethality, illustrating its indispensability[2][3][4]. In humans, loss-of-function mutations are highly constrained and associated with neurodevelopmental disease, suggesting an essential conserved function without redundancy among gamma cluster members[2][3][4][1]. No specific drugs, biomarkers, or safety concerns are associated for therapeutic targeting as of current research[1][2][3][4].

Other names

PCDHGC4Protocadherin gamma subfamily C, 4Protocadherin gamma-C4PCDH-gamma-C4PCDH-GAMMA-C4NEDGS