Family with sequence similarity 20 member C (FAM20C) (FAM20C)

Family with sequence similarity 20 member C (FAM20C) is a Golgi-associated serine/threonine protein kinase that phosphorylates secreted proteins containing Ser-x-Glu/pSer motifs as well as other related motifs[1][3][5]. FAM20C is the physiological casein kinase of the secretory pathway, controlling the phosphorylation of hundreds of substrates involved in biomineralization, calcium homeostasis, wound healing, lipid metabolism, and neuropeptide function[1][2][4][7]. Pathogenic variants in FAM20C cause Raine syndrome, a severe, often lethal, osteosclerotic skeletal disorder characterized by abnormal bone formation and systemic complications[2][5]. FAM20C is also implicated in cancer progression—particularly glioma and breast cancer—where it promotes tumor invasion and metastasis[4][6]. Experimental inhibitors of FAM20C are in development as potential anti-cancer therapeutics. Due to its broad tissue expression and substrate scope, FAM20C is central to multiple physiological systems but also presents risks for broad off-target effects when used as a therapeutic target[1][4][6][7].

Other names

Golgi casein kinaseGolgi-enriched fraction casein kinase (GEF-CK)Dentin matrix protein 4 (DMP4)Extracellular serine/threonine protein kinase FAM20CDMP-4G-CKRNSfamily with sequence similarity 20, member C

Inhibition of FAM20C kinase activity (reduces phosphorylation of secreted proteins, can block tumor invasion and growth in preclinical models); Modulation of calcium and phosphate homeostasis by altering phosphorylation status of biomineralization proteins