Copy number variations in AKAP11 in patients diagnosed with bipolar I disorder associated with misfolding of protein and inability to bind to GSK3b.

Type I bipolar disorder (BD-I) is a heritable mood disorder affecting about 2.3 million Americans and causes an individual to cycle between manic and depressive episodes (Bipolar disorder, n.d.). These periods must last longer than seven days to be considered an episode, and these phases can be medically severe. It is important to find the genetic cause for BD-I because the current medication, lithium, is not an effective long-term treatment; less than half of diagnosed patients respond to it. Understanding the biological cause may allow scientists to manufacture a treatment specifically made to target the genetic variation. Previous studies examined how the mutation in the exome of the A-kinase anchoring protein 11 (AKAP11) was most seen in patients with BD-I (Palmer, 2022). AKAP11 binds to the Glycogen synthase kinase-3 beta (GSK3b), an essential protein for BD-I, and facilitates its phosphorylation (Dema et al., 2016). Moreover, studies on copy number variations (CNVs) in A-kinase anchoring protein 5 (AKAP5) were found in individuals diagnosed with general bipolar disorder (Wilson, 2006). CNVs are known to be detrimental and can cause a change in gene expression and the folding of proteins (Tang & Amon, 2013). I hypothesized that patients with BD-I are more likely to have an increase in CNVs in the AKAP11 causing it to misfold because of similar CNVs occurring in the AKAP family, leading to detrimental illnesses. I compared research papers (n=4) including information on different AKAPs and the effects of the CNVs found in each protein on an individual. Preliminary results indicate that it is possible CNVs are found in the AKAP11 because of its existence in other AKAPs and the detrimental phenotypic changes that result in these genetic variations.