This report describes pseudohypoaldosteronism, type IIC (PHA2C), which is a subtype of pseudohypoaldosteronism, type II; PHA2C exhibits autosomal dominant inheritance. The human gene implicated in this disease is WNK1, which is a serine-threonine protein kinase involved in regulation of of renal electrolyte transport. WNK1 is also implicated in a form of neuropathy (MIM:201300). There is a single orthologous gene in Drosophila, Dmel\Wnk, which is also orthologous to WNK2, WNK3, and WNK4. WNK4 is implicated in another form of pseudohypoaldosteronism (PHA2B, FBhh0000635). 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).
A UAS construct of the human Hsap\WNK1 gene has been introduced into flies, but has not been characterized in the context of a human disease model.
[updated Sep.2017 by FlyBase; FBrf0222196]
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 IIC; PHA2C](https://omim.org/entry/614492)
[PROTEIN KINASE, LYSINE-DEFICIENT 1; WNK1](https://omim.org/entry/605232)
See general description, above.
Pseudohypoaldosteronism type IIC (PHA2C) is caused by heterozygous mutation in the WNK1 gene. [from MIM:614492; 2017.09.28]
The WNK1 (WNK lysine deficient protein kinase 1) gene encodes a member of the WNK subfamily of serine-threonine protein kinases. It acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters, respectively, via interactions with WNK4. The WNK1 protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. [Gene Cards, WNK1; 2017.09.28]
Alternative splicing of WNK1 produces a kidney-specific short form that lacks a kinase domain, KS-WNK1, and a more ubiquitous long form, L-WNK1 (Wade et al., 2006; pubmed:16709664). 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.
