WNK4

At least eight mutations in the WNK4 gene have been found to cause pseudohypoaldosteronism type 2 (PHA2), a condition characterized by high blood pressure (hypertension) and high levels of potassium in the blood (hyperkalemia). The mutations involved in this condition change single protein building blocks (amino acids) in the WNK4 protein. The alterations to the WNK4 protein impair its breakdown, resulting in higher than normal levels of WNK4 protein and elevated WNK4 activity. The increase in WNK4 activity leads to increased sodium reabsorption and reduced potassium secretion, resulting in hypertension and hyperkalemia.

Studies have associated normal variations in the WNK4 gene with an increased risk of high blood pressure (hypertension) in people without pseudohypoaldosteronism type 2. A combination of genetic variations and environmental factors likely influence the development of this complex condition.