{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRHAG is a member of the Rh‐protein family that functions as a gas channel in erythrocytes and in heterologous expression systems. Studies have demonstrated that RHAG mediates transmembrane transport of ammonia and ammonium, contributing to both NH₃ influx and NH₄⁺/H⁺ exchange, and has measurable permeability for CO₂ as well. In Xenopus oocytes and red cell membrane ghosts, enhanced surface pH changes and altered gas fluxes indicate that RHAG facilitates the movement of these gaseous and ionic species, thereby playing a major role in cellular gas exchange and acid–base balance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the mechanistic level, RHAG exhibits distinct transporter characteristics that are sensitive to the transmembrane pH gradient, indicating that ammonium uptake can occur in an electrogenic or electroneutral manner depending on the prevailing ionic conditions. Its molecular structure is consistent with forming a pore‐like assembly that allows passage of NH₃ and, to some extent, NH₄⁺ across the plasma membrane. Moreover, RHAG is integral to the assembly and proper surface expression of the Rh complex in red cells—a function that is critical for maintaining efficient gas exchange and membrane integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutational analyses have underscored the physiological and clinical importance of RHAG’s transporter function. Several studies have reported that missense and nonsense mutations in the RHAG gene can lead to loss or alteration of gas channel activity, resulting in aberrant ammonium transport and even abnormal monovalent cation leakage. Such defects are mechanistically linked to the Rh_null, Rh_mod, and overhydrated hereditary stomatocytosis phenotypes, where improper assembly of the Rh complex and reduced gas permeability compromise red blood cell function. 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