Neurological, and nephrological disorders

Neuropathy; Hereditary sensory neuropathy (CIP, HSAN, HSN); Pseudohypoaldosteronism (PHA) ; Hereditary sensory and autonomic neuropathy Type 1i (HSAN2, HSAN2A); Pseudohypoaldosteronism Type 1i (DA3); Autonomic neuropathy; Pseudohypoaldosteronism Type 1ic; Gitelman syndrome (GS); Hereditary sensory and autonomic neuropathy Type 1ia; Pseudohypoaldosteronism Type 1ib (PHA2)

Hereditary Sensory Neuropathy (CIP, HSAN, HSN) is a rare condition that is characterized by congenital insensitivity to pain, and is a disorder which can affect bone, spinal cord, and brain. Pseudohypoaldosteronism (PHA) is a rare nephrological disorder characterized by the lack of response to aldosterone, leading to a lack of feedback inhibition and therefore higher aldosterone levels. PHA can affect the lung, colon, and skin. Hereditary Sensory and Autonomic Neuropathy Type Ii (HSAN2, HSAN2A) is a rare condition that affects sensory neurons, and rarely affects autonomic nervous system nerves leading to abnormal heart rate, digestion, and breathing. HSAN2 can affect heart and bone. Pseudohypoaldosteronism Type Ii (DA3) is a rare condition characterized by camptodactylyl, clubfoot, and periodicially characterized by cleft palate. DA3 is idiopathic, but is believed to be an x-linked association. Pseudohypoaldosteronism Type Iic is a rare condition related to Pseudohypoaldosteronism Type Iib. Gitelman Syndrome (GS) is a rare condition leading to the imbalance of potassium, calcium, and magnesium. Hereditary Sensory and Autonomic Neuropathy Type Iia is a rare condition. Pseudohypoaldosteronism Type Iib (PHA2) is related to Pseudohypoaldosteronism.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Barrett's esophagus epithelial metaplasia (%CFC= -45, p<0.039); Bladder carcinomas (%CFC= +56, p<0.015); Brain glioblastomas (%CFC= +84, p<0.054); Cervical cancer (%CFC= +81, p<0.006); Colorectal adenocarcinomas (early onset) (%CFC= +58, p<0.038); and Gastric cancer (%CFC= -65, p<0.026). The COSMIC website notes an up-regulated expression score for WNK1 in diverse human cancers of 527, which is 1.1-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 62 for this protein kinase in human cancers was 1-fold of the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.06 % in 25303 diverse cancer specimens. This rate is only -22 % lower than the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.3 % in 1119 large intestine cancers tested; 0.21 % in 589 stomach cancers tested; 0.2 % in 805 skin cancers tested; 0.15 % in 602 endometrium cancers tested; 0.11 % in 500 urinary tract cancers tested; 0.1 % in 1753 lung cancers tested; 0.05 % in 904 ovary cancers tested; 0.05 % in 1560 breast cancers tested; 0.05 % in 1270 liver cancers tested; 0.04 % in 1226 kidney cancers tested; 0.02 % in 1942 haematopoietic and lymphoid cancers tested.

None > 7 in 20,587 cancer specimens

Twenty-two deletions (19 at K583fs*11), 4 insertions and no complex mutations are noted on the COSMIC website.