This report describes pseudohypoaldosteronism, type IIC (PHA2B), which is a subtype of pseudohypoaldosteronism, type II; PHA2B exhibits autosomal dominant inheritance. The human gene implicated in this disease is WNK4, which is a serine-threonine protein kinase involved in regulation of of renal electrolyte transport. There is a single orthologous gene in Drosophila, Dmel\Wnk, which is also orthologous to WNK1, WNK2, and WNK3. WNK1 is implicated in another form of pseudohypoaldosteronism (PHA2C, FBhh0000634). Information about a fly model for these two related diseases can be found in the human disease model report 'pseudohypoaldosteronism, type II, WNK-related' (FBhh0000636).
People with Pseudohypoaldosteronism type 2 (PHA2) have high blood pressure (hypertension) and high levels of potassium in their blood (hyperkalemia) despite having normal kidney function. The age of onset of PHA2 is variable and difficult to pinpoint; some affected individuals are diagnosed in infancy or childhood, and others are diagnosed in adulthood. Hyperkalemia usually occurs first, and hypertension develops later in life. Affected individuals also have high levels of chloride (hyperchloremia) and acid (metabolic acidosis) in their blood (together, referred to as hyperchloremic metabolic acidosis). [Genetics Home Reference, pseudohypoaldosteronism type 2; 2017.09.28]
Pseudohypoaldosteronism type II (PHA2) is characterized by hyperkalemia despite normal renal glomerular filtration, hypertension, and correction of physiologic abnormalities by thiazide diuretics. [from MIM:145260; 2017.09.28]
[PSEUDOHYPOALDOSTERONISM, TYPE IIB; PHA2B](https://omim.org/entry/614491)
[PROTEIN KINASE, LYSINE-DEFICIENT 4; WNK4](https://omim.org/entry/601844)
See general description, above.
Pseudohypoaldosteronism type IIB (PHA2B) is caused by heterozygous mutation in the WNK4 gene. [from MIM:614491; 2017.09.28]
The WNK4 (WNK lysine deficient protein kinase 4) gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. [Gene Cards, WNK4; 2017.09.28]
WNK4 is an integrative regulator of renal electrolyte transport whose main target is the thiazide-sensitive Na-Cl cotransporter SLC12A3 (Wu and Peng, 2013; pubmed:23665031). [from MIM:601844; 2017.09.28]
WNK1, WNK4, and the kidney-specific WNK1 isoform interact to regulate SLC12A3 activity, suggesting that WNKs form a signaling complex (Yang et al., 2007; pubmed:17975670). [from MIM:605232; 2017.09.28]
Many to one (4 human to 1 Drosophila); the human genes are WNK1 WNK2, WNK3, and WNK4.
