Infectious disease, and neuronal disorders

Influenza; Alexander disease

p38a is implicated in the pathophysiology of inflammatory bowel disease. It may be a potential therapeutic target for spinal muscle atrophy, which is an autosomal recessive neurodegenerative disease characterized by progressive muscle atrophy. Spinal muscle atrophy results from deletion or mutation of SMN1 gene, which can be induced by p38a activitation.
 

p38a may be also involved in drug resistance development of acute myeloid leukemias.
 

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: Brain glioblastomas (%CFC= +221, p<0.012); and Brain oligodendrogliomas (%CFC= +193, p<0.06). The COSMIC website notes an up-regulated expression score for p38a in diverse human cancers of 565, which is 1.2-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 152 for this protein kinase in human cancers was 2.5-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: 0.08 % in 25411 diverse cancer specimens. This rate is very similar (+ 6% higher) 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: 0.48 % in 805 skin cancers tested; 0.38 % in 1093 large intestine cancers tested.

None > 4 in 20,694 cancer specimens

Only 2 deletions, 3 insertions, and no complex mutations are noted on the COSMIC website.