Camk2a, also known as calcium/calmodulin-dependent protein kinase II alpha, is a key calcium signaling molecule. It is involved in the glutamatergic signaling pathway and plays essential roles in multiple biological processes. It has been shown to be crucial for normal learning and synaptic plasticity [1,2].

Mutations in Camk2a have been associated with intellectual disability. Rare de novo variants in Camk2a can affect its auto-phosphorylation at Thr286, which in turn impacts neuronal migration, highlighting the importance of tightly regulated auto-phosphorylation in neuronal function and neurodevelopment [1]. In a Camk2a knockout mouse model, adult reinstatement of the Camk2a gene can rescue behavioral and electrophysiological phenotypes, including spatial and conditional learning and synaptic plasticity, suggesting it does not have a critical irreversible role in neurodevelopment [2].

In summary, Camk2a is vital for normal brain function, especially in learning and synaptic plasticity. Studies using gene knockout mouse models have provided valuable insights into its role in intellectual disability and neurodevelopment, suggesting potential therapeutic implications for Camk2a-related disorders [1,2].

References:

1. Küry, Sébastien, van Woerden, Geeske M, Besnard, Thomas, Elgersma, Ype, Mercier, Sandra. . De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. In American journal of human genetics, 101, 768-788. doi:10.1016/j.ajhg.2017.10.003. https://pubmed.ncbi.nlm.nih.gov/29100089/

2. Rigter, Pomme M F, Wallaard, Ilse, Aghadavoud Jolfaei, Mehrnoush, Elgersma, Ype, van Woerden, Geeske M. 2022. Adult Camk2a gene reinstatement restores the learning and plasticity deficits of Camk2a knockout mice. In iScience, 25, 105303. doi:10.1016/j.isci.2022.105303. https://pubmed.ncbi.nlm.nih.gov/36304100/