Musculoskeletal disorders

Myotonic dystrophy

Myotonic dystrophy is an inherited disease that affects multiple systems of the body. Symptoms include the wasting of the muscles (muscular dystrophy), cataracts, heart defects, endocrine dysfunction, and myotonia.
 

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= +77, p<0.0002); Breast epithelial cell carcinomas (%CFC= +60, p<0.013); Pituitary adenomas (ACTH-secreting) (%CFC= +97); and Skin squamous cell carcinomas (%CFC= +124, p<0.021). The COSMIC website notes an up-regulated expression score for MRCKb in diverse human cancers of 376, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 325 for this protein kinase in human cancers was 5.4-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. The MRCK-ß protein posesses many functional domains, including three independent coiled-coil (CC) domains involved in the dimerization that is critical for the activation of the protein, a cysteine-rich motif similar to that of protein kinase C (PKC), and potentially a pleckstrin homology (PH) domain. Deletion of the two distal CC domains (CC2 and CC3; amino acid residues 658-930) results in a constitutively active kinase, indicating a role for these domains in the autoinhibition of the kinase catalytic domain of the protein.

Percent mutation rates per 100 amino acids length in human cancers: 0.06 % in 24972 diverse cancer specimens. This rate is only -18 % 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: 0.24 % in 864 skin cancers tested; 0.22 % in 1272 large intestine cancers tested; 0.2 % in 589 stomach cancers tested; 0.18 % in 603 endometrium cancers tested; 0.15 % in 548 urinary tract cancers tested; 0.13 % in 273 cervix cancers tested; 0.12 % in 710 oesophagus cancers tested; 0.09 % in 127 biliary tract cancers tested; 0.08 % in 1822 lung cancers tested; 0.07 % in 238 bone cancers tested; 0.06 % in 1512 liver cancers tested; 0.06 % in 1372 breast cancers tested; 0.04 % in 942 upper aerodigestive tract cancers tested; 0.04 % in 833 ovary cancers tested; 0.04 % in 1276 kidney cancers tested; 0.03 % in 881 prostate cancers tested; 0.03 % in 2082 central nervous system cancers tested; 0.03 % in 1459 pancreas cancers tested; 0.01 % in 2009 haematopoietic and lymphoid cancers tested.

None > 3 in 20,256 cancer specimens

Only 6 deletions, 2 insertions and no complex mutations are noted on the COSMIC website.