Nephrological, neuronal, and liver disorders

Polycystic kidney disease, Type 2 (PKD2); kidney disease; Polycystic kidney disease (PKD, PKD1); Polycystic kidney disease, autosomal dominant (ADPKD); Polycystic Liver disease (PCLD); Cystic kidney; Liver disease; Intracranial aneurysm; Polycystic kidney disease, Type 1

Polycystic Kidney Disease, Type 2 (PKD2) is a rare nephrological disorder related to polycystic kidney disease (PKD) which is characterized by formation of cysts in the kidney, and can possibly lead to kidney failure. Kidney Disease is related to PKD2. Polycystic Kidney Disease, Autosomal Dominant (ADPKD) is a rare inherited disease characterized by development of cysts in the kidney. The rare inherited liver condition Polycystic Liver Disease (PCLD) is characterized by abdominal pain, liver swelling, and cyst development in the liver. Liver disease is also referred to as liver disorder in pregnancy and it is a rare condition that has a relation to hepatitis and fatty liver disease. Intracranial Aneurysm is characterized by the ballooning, or bulging of an artery in the brain leading to a brain aneurysm. For PKD2 the S244E, S706E, and S710E mutations, in conjunction, will lead to constitutive kinase phosphotransferase activity. A marginal increase in the ability of PKD2 to bind DAG and a great increase in PKD2 to bind phorbol ester occurs with a P275G mutation. Phosphorylation of PKD2 is lost with a Y438F mutation. Full loss of kinase phosphotransferase activity in PKD2 can occur with a D695A 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= +61, p<0.026); Brain glioblastomas (%CFC= -69, p<0.006); Classical Hodgkin lymphomas (%CFC= -49, p<0.101); Clear cell renal cell carcinomas (cRCC) (%CFC= +52, p<0.092); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -70, p<0.0001); Large B-cell lymphomas (%CFC= +88, p<0.048); and Ovary adenocarcinomas (%CFC= +56, p<0.098). The COSMIC website notes an up-regulated expression score for PKD2 in diverse human cancers of 421, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 161 for this protein kinase in human cancers was 2.7-fold of 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: 0.07 % in 24726 diverse cancer specimens. This rate is only -2 % lower and is very similar to 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 1270 large intestine cancers tested; 0.28 % in 864 skin cancers tested; 0.25 % in 589 stomach cancers tested; 0.23 % in 603 endometrium cancers tested; 0.18 % in 127 biliary tract cancers tested; 0.15 % in 833 ovary cancers tested; 0.15 % in 548 urinary tract cancers tested; 0.11 % in 1634 lung cancers tested; 0.08 % in 273 cervix cancers tested; 0.05 % in 238 bone cancers tested; 0.05 % in 1512 liver cancers tested; 0.05 % in 1316 breast cancers tested; 0.04 % in 2009 haematopoietic and lymphoid cancers tested; 0.04 % in 1276 kidney cancers tested; 0.03 % in 881 prostate cancers tested; 0.03 % in 710 oesophagus cancers tested; 0.03 % in 441 autonomic ganglia cancers tested; 0.03 % in 2103 central nervous system cancers tested; 0.02 % in 558 thyroid cancers tested; 0.02 % in 1459 pancreas cancers tested.

None > 4 in 19,781 cancer specimens

Only 3 deletions, 2 insertions, and no complex mutations are noted on the COSMIC website.