Figure 3. Germline mutations in PKC associated with disease.

LOF mutations that are causative in a proliferative disease are a hallmark of a bonafide tumor suppressor: indicated are the positions of such germline mutations that have been identified in several families with lymphoproliferative syndrome; X indicates position of biallelic splice mutation that results in no expression of protein. In contrast to LOF mutations, germline mutations that enhance the activity of PKC are associated with degenerative diseases: indicated are rare variants in PKCα that segregated with affected family members with late onset Alzheimer's Disease, the multiple mutations in PKCγ that are causative in spinocerebellar ataxia type 14, and a variant in PKCη that is associated with increased risk to stroke.