Heart disorders

Arrhythmogenesis

O-GlcNAc binding to CaMK2a at S279 will result in activation, which can lead to an arrhythmia of the heart. CaMK2I inhibition may substantially reduce maladaptive remodeling from excessive beta-adrenergic receptor stimulation and myocardial infarction, and induce balanced changes in excitation-contraction coupling that preserve baseline and beta-adrenergic rceeptor-stimulated physiological increases in cardiac function.
 

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 Bladder carcinomas (%CFC= -55, p<0.012). The COSMIC website notes an up-regulated expression score for CaMK2a in diverse human cancers of 240, which is 48% lower than the average score of 462 for the human protein kinases. The down-regulated expression score of 1 for this protein kinase in human cancers was 98% 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: 0.08 % in 24727 diverse cancer specimens. This rate is only 13 % 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: 0.57 % in 589 stomach cancers tested; 0.39 % in 864 skin cancers tested; 0.31 % in 603 endometrium cancers tested; 0.3 % in 1270 large intestine cancers tested; 0.23 % in 273 cervix cancers tested.

None > 3 in 20,010 cancer specimens

Only 1 deletion, and no insertions or complex mutations are noted on the COSMIC website.