KCNJ1

KCNJ1 is a human gene that encodes the Kir1.1 inward-rectifier potassium channel subunit, also known as ROMK1. Kir1.1 channels form homotetrameric potassium-selective channels that preferentially pass current into the cell at resting membrane potentials. In the kidney, ROMK channels are expressed on the apical membranes of tubular epithelia in the thick ascending limb of the loop of Henle and in the collecting duct, where they participate in potassium recycling necessary for renal salt handling and potassium secretion in the distal nephron.

Function and regulation: Kir1.1 channels contribute to establishing and maintaining electrochemical gradients essential for renal potassium balance. Their activity is modulated by intracellular nucleotides and lipids, including ATP, magnesium, and PIP2, and can be influenced by signaling pathways and kinases. The gene produces multiple isoforms via alternative splicing, contributing to channel diversity.

Clinical significance: Mutations in KCNJ1 cause Bartter syndrome type II, a salt-wasting tubulopathy characterized by hypokalemia, metabolic alkalosis, polyuria, and normal to reduced growth. Neonatal or infancy-onset presentations are common, sometimes with antenatal polyhydramnios. The pathology reflects impaired potassium recycling in the thick ascending limb and reduced potassium availability for secretion in the distal nephron, leading to renal potassium loss.

Treatment and management: Management focuses on correcting fluid and electrolyte imbalances. Potassium-sparing diuretics (for example, amiloride or triamterene) may be used to reduce renal potassium loss by inhibiting ROMK-mediated secretion. KCNJ1 is part of the broader family of Kir inward-rectifier channels, sharing structural features that include a pore-forming transmembrane core and cytoplasmic domains involved in regulation and assembly.