KCNB2, encoding a component of voltage-gated potassium channels, is crucial for regulating neuronal excitability and synaptic transmission. It is involved in key neuronal processes, and its malfunction can disrupt normal neurodevelopment. Potassium channels, of which KCNB2 is a part, mediate voltage fluxes in excitable cells like neurons [1,2].

Mutations in KCNB2 are associated with various neurodevelopmental disorders (NDDs). Mono-allelic pathogenic missense variants in KCNB2 lead to a neurodevelopmental syndrome with epilepsy and autism in some cases. These variants typically alter potassium channel inactivation, resulting in hyper-excitability of neurons, which contributes to disease manifestations [1,2]. In addition, the KCNB2 rs349358 SNP is an independent predictor of postoperative nausea and vomiting (PONV), and a genetic risk score based on it and another SNP has a similar impact on PONV susceptibility compared to the Apfel Score [3,4].

In conclusion, KCNB2 is essential for normal neuronal function through its role in regulating potassium channels. Its dysfunction, often due to genetic variants, is linked to NDDs and PONV. The study of KCNB2 using genetic models helps to understand its role in these disease conditions, potentially leading to the development of targeted therapies for affected individuals.

References:

1. Mohamed, Zakaria Ahmed, Li, Jinghua, Wen, Jianping, Jia, Feiyong, Banerjee, Santasree. 2024. The KCNB2 gene and its role in neurodevelopmental disorders: Implications for genetics and therapeutic advances. In Clinica chimica acta; international journal of clinical chemistry, 566, 120056. doi:10.1016/j.cca.2024.120056. https://pubmed.ncbi.nlm.nih.gov/39577484/

2. Bhat, Shreyas, Rousseau, Justine, Michaud, Coralie, Blunck, Rikard, Campeau, Philippe M. 2024. Mono-allelic KCNB2 variants lead to a neurodevelopmental syndrome caused by altered channel inactivation. In American journal of human genetics, 111, 761-777. doi:10.1016/j.ajhg.2024.02.014. https://pubmed.ncbi.nlm.nih.gov/38503299/

3. Klenke, Stefanie, de Vries, Gudrun J, Schiefer, Laura, Peters, Jürgen, Frey, Ulrich H. 2019. Genetic contribution to PONV risk. In Anaesthesia, critical care & pain medicine, 39, 45-51. doi:10.1016/j.accpm.2019.04.012. https://pubmed.ncbi.nlm.nih.gov/31077873/

4. Klenke, Stefanie, Frey, Ulrich H. . Genetic variability in postoperative nausea and vomiting: A systematic review. In European journal of anaesthesiology, 37, 959-968. doi:10.1097/EJA.0000000000001224. https://pubmed.ncbi.nlm.nih.gov/32371828/