Cancer, neurological, endocrine, and musculoskeletal disorders

Alzheimer's disease (AD); Amyotrophic lateral sclerosis (ALS); Neuronitis; Parkinson disease; Diabetes

Alzheimer's disease is characterized by an accumulation of p25. CDK5 kinase levels rise with increased p25 levels, but it was not shown to be causative. Binding of p35 or p25 to CDK5 can be impaired with a CDK5 S159T mutation. ALS is a rare motor neuron disease resulting in loss of control over muscle movement. Neuronitis results in loss of motor control, and is associated with BET1 (a golgi vesicular membrane trafficking protein). CDK5 may also contribute to pathogenicity in Parkinson Disease. CDK5 signalling can lead to phosphorylation of a nuclear receptor, PPARG. This CDK5-PPARG pathway has been suggested to have a role in insulin resistance for diabetes.
 

Neuroblastomas (NB); Aneurysmal bone cysts (ABC)

CDK5 has been implicated in Aneurysmal bone cyst, which is a bone cancer that will affect bone, endothelial tissue, and bone marrow.
 

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= +89, p<0.0001); Cervical cancer (%CFC= -63, p<0.013); Cervical cancer stage 2A (%CFC= +60, p<0.081); Colon mucosal cell adenomas (%CFC= +69, p<0.0001); Large B-cell lymphomas (%CFC= +48, p<0.002); Lung adenocarcinomas (%CFC= +95, p<0.0001); and Oral squamous cell carcinomas (OSCC) (%CFC= +115, p<0.027). The COSMIC website notes an up-regulated expression score for CDK5 in diverse human cancers of 621, which is 1.3-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 28 for this protein kinase in human cancers was 0.5-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: 0.06 % in 24196 diverse cancer specimens. This rate is only -27 % 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: 0.31 % in 1093 large intestine cancers tested.

None > 2 in 20,222 cancer specimens

Only 1 deletion and 1 insertion and no complex mutations are noted on the COSMIC website.