Monday, March 7, 2016

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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