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FB2026_02
,
released June 18, 2026
This report describes pseudohypoaldosteronism, type II, WNK-related, which includes models of pseudohypoaldosteronism using the Drosophila Wnk gene. Dmel\Wnk is orthologous to 4 human genes, two of which are implicated in autosomal dominant forms of pseudohypoaldosteronism (see 'pseudohypoaldosteronism, type IIC', MIM:614492, FBhh0000634; and 'pseudohypoaldosteronism, type IIB', MIM:614491, FBhh0000635). The WNK genes are serine-threonine protein kinases involved in regulation of transport of sodium and chloride ions. Loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Wnk.
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.
Homozygous loss-of-function mutations of Dmel\Wnk are lethal. Targeted decrease of Wnk, effected by RNAi or a dominant-negative mutation, in the principal cells of the Malpighian tubules decreases trans-epithelial potassium ion flux in the tubules. Genetic and physical interactions have been reported for Dmel\Wnk; see below and in the Wnk gene report.
[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]
Many to one (4 human to 1 Drosophila); the human genes are WNK1 WNK2, WNK3, and WNK4.
Many to one (4 human to 1 Drosophila); the human genes are WNK1 WNK2, WNK3, and WNK4.
Moderate-scoring ortholog of four genes in human (1 Drosophila to 4 human): WNK1 WNK2, WNK3, and WNK4. Dmel\Wnk shares 26-28% identity and 37-42% similarity with the human genes.