Rh family C glycoprotein (RHCG)

Rh family C glycoprotein (RHCG) is a membrane-bound transporter belonging to the Rhesus (Rh) family, which conducts ammonia (NH₃) and possibly carbon dioxide (CO₂) across epithelial cell membranes, playing a critical role in renal pH regulation, ammonia excretion, and acid-base balance[2][4][7][9][11]. Structurally, RHCG forms a trimeric complex with 12 transmembrane helices, providing an ammonia-specific conduction channel informative for human renal physiology[2][7][11]. It is widely expressed in tissues where ammonia metabolism is essential, especially the kidney and various squamous epithelia[1][4][9]. Beyond physiological functions, RHCG also exhibits tumor suppressor activity, notably in squamous cell carcinomas, where its downregulation is associated with poor prognosis and increased tumorigenicity due to promoter hypermethylation[1]. In addition, RHCG acts as a pathogenic factor in diseases like psoriasis, where pharmacological agents may affect its expression and disease outcomes[3][8]. Disease associations also include hereditary stomatocytosis and hemolytic diseases related to Rh antigen involvement, but RHCG itself does not serve as a classic blood group antigen[4][9]. Extensive structural and functional studies underscore its emerging roles in cancer prognosis and systemic acid-base physiology.

Other names

Ammonium transporter Rh type CC15orf6CDRC2PDRC2RHGKSLC42A3Rh glycoprotein kidneyRhesus blood group family type C glycoproteinTumor-related protein DRC2

Downregulation of RHCG expression and associated downstream signaling in psoriasis (secukinumab); Modulation of expression and related pathways (e.g., methotrexate, glucocorticoids)