WNK Pathway Involvement in Disease: A Brief Overview

The importance of the WNK pathway in physiology is best understood via its involvement in a wide variety of diseases. The majority of studies have focused on the role of WNKs in hypertension, in particular the roles of these enzymes in the kidney. However, studies of WNKs in other, non-renal tissues are few, and there is a need  to characterize the functions and mechanisms of action of these enzymes outside the kidney.

Disease	Mutated/Altered Proteins	References
PHA II/Familial Hyperkalaemic Hypertension (FHHt)/Gordon’s syndrome	WNK1 WNK4 Cullin 3 KLHL3	(4, 21, 47)
Gitelman’s syndrome	SLC12A3 (NCC) CLCNKB (ClC-Kb)	(12, 15, 22, 37)
Bartter’s syndrome	SLC12A1 (NKCC2) KCJN1 (ROMK) CLCNKB (ClC-Kb) BSND (barttin) CASR (CasR)	(2, 5, 18, 19, 29, 36, 44)
Liddle’s syndrome	SCNN1 (ENaC)	(35)
Andermann’s syndrome	SLC12A6 (KCC3)	(14)
EAST (Epilepsy, ataxia, sensorineural deafness, and tubulopathy)/SeSAME (seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance) syndrome	KCJN10 (Kir4.1)	(3, 34)
Essential Hypertension	WNK1 WNK4 Stk39 (SPAK) SGK1 Nedd4-2	(7, 9-11, 16, 17, 27, 28, 41-43, 45, 46)
Hereditary Sensory and Autonomic Neuropathy Type II	WNK1	(20, 32, 33)
Autism	WNK3	(31)
Schizophrenia	WNK3 OXSR1 (OSR1)	(1)
Osteoporosis	WNK1	(48)
Cancer	WNK1 WNK2 WNK3 WNK4 SLC12A6 (KCC3) Stk39 (SPAK)	(6, 8, 13, 23-26, 30, 38-40)

References:

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