Cardiovascular, and nephrological disorders

Hypertension (HTN); Diabetic nephropathy

Hypertension (HTN) is a rare cardiovascular disorder that manifests as high blood pressure causing a higher risk of stroke, heart failure, heart attack, and kidney failure. SGK kinase phosphotransferase activity can be fully abolished with a K127M mutation, or it can be partly inhibited with one of the T256A, T256D, T256E, or S422A mutations. A 10-fold increase in phosphotransferase activity has been noted with a S422-D mutation. NEDD4 and NEDD4L complex formation with SGK can be inhibited with a Y298A mutation.
 

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: Bladder carcinomas (%CFC= -55, p<0.002); Brain glioblastomas (%CFC= -82, p<0.002); Brain oligodendrogliomas (%CFC= -68, p<0.011); Cervical epithelial cancer (%CFC= +45, p<0.022); Cervical cancer (%CFC= +178, p<0.0001); Classical Hodgkin lymphomas (%CFC= +286, p<(0.0003); Colon mucosal cell adenomas (%CFC= -70, p<0.0001); Colorectal adenocarcinomas (early onset) (%CFC= +72, p<0.058); Gastric cancer (%CFC= -48, p<0.0009); Large B-cell lymphomas (%CFC= +899, p<0.005); Lung adenocarcinomas (%CFC= -47, p<0.0002); Ovary adenocarcinomas (%CFC= -65, p<0.002); Pituitary adenomas (aldosterone-secreting) (%CFC= -54, p<0.057); Skin melanomas - malignant (%CFC= +88, p<0.004); Uterine fibroids (%CFC= -65, p<0.0009); and Uterine leiomyomas from fibroids (%CFC= -79, p<0.083). The COSMIC website notes an up-regulated expression score for SGK in diverse human cancers of 312, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.12 % in 25490 diverse cancer specimens. This rate is a modest 1.54-fold higher 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: 0.54 % in 603 endometrium cancers tested; 0.31 % in 895 skin cancers tested; 0.3 % in 2096 haematopoietic and lymphoid cancers tested; 0.27 % in 1270 large intestine cancers tested; 0.25 % in 548 urinary tract cancers tested; 0.18 % in 1967 lung cancers tested; 0.18 % in 127 biliary tract cancers tested; 0.16 % in 1276 kidney cancers tested; 0.12 % in 589 stomach cancers tested; 0.12 % in 1512 liver cancers tested; 0.07 % in 710 oesophagus cancers tested; 0.07 % in 1316 breast cancers tested; 0.06 % in 2082 central nervous system cancers tested; 0.05 % in 441 autonomic ganglia cancers tested; 0.04 % in 558 thyroid cancers tested.

Most frequent mutations with the number of reports indicated in brackets: P77S (3).

Ten deletions, 2 insertions and 1 complex mutations are noted on the COSMIC website.