Cancer, immune disorders

Immunodeficiency, common variable, 9; Common variable Immune deficiency; Autoimmune lymphoproliferative syndrome, Type 1b; Systemic lupus erythematosus 16

Reduced PKCd expression or activity is associated with immunodeficiency, common variable, 9, which is a primary immunodeficiency and results in B-cell deficiency and severe autoimmunity. Mutations are also associated with autoimmune lymphoproliferative syndrome type III, indicating this gene has a crucial role in regulating B-cell tolerance and preventing self-reactivity in humans.
 

ACTH-secreting pituitary adenomas

PKCd may be a tumour suppressor protein (TSP). PKCd negatively regulates cell proliferation in colon cell lines. It is also required for ErbB2-driven mammary gland tumorigenesis, and negatively correlates with prognosis in human breast cancer.
 

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= +134, p<0.0005); Brain glioblastomas (%CFC= +4697, p<0.0001); Brain oligodendrogliomas (%CFC= +10153, p<0.0001); Breast epithelial cell carcinomas (%CFC= +74, p<0.01); Cervical cancer (%CFC= +61, p<0.011); Skin fibrosarcomas (%CFC= -48); and Skin melanomas - malignant (%CFC= +569, p<0.0001). The COSMIC website notes an up-regulated expression score for PKCd in diverse human cancers of 336, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 119 for this protein kinase in human cancers was 2-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: 0.07 % in 25347 diverse cancer specimens. This rate is only -4 % 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: 0.51 % in 1093 large intestine cancers tested; 0.35 % in 805 skin cancers tested.

Most frequent mutations with the number of reports indicated in brackets: R6L (4); R6H (2).

Only 5 deletions (all at D434fs*2), 2 insertions (1 at D434fs*13), and no complex mutations are noted on the COSMIC website. About 32% of the point mutations are silent and do not change the amino acid sequence of the protein kinase.