Role of Methylation in Regulation and Physiology of 5HT2C Gene in the Brain and Plausible Impact of Cys23ser Polymorphism: A Bioinformatics Approach

Signal transduction through G-proteins is a prominent feature of several eukaryotes. 5-HT2C receptor, a G-protein-coupled receptor (GPCR), is a candidate of interest for the treatment of several neuropsychiatric diseases owing to its expression profile, signalling, and neuronal functions. In this mini-review and analysis paper, we provide background literature on the unique biochemical, structural, pharmacological, and genetics of the 5-HT2c receptor. We conduct in silico epigenetic analysis of the promoter and flanking regions and histone marks. Further, evolutionary and phylogenetic analysis of the 5HT2C gene and Cys23ser substitution using bioinformatics tools. Our results implicate alterations in DNA methylation and associated regulatory elements in the promoter and upstream which could impact gene expression, inactivation, genome stabilization, and inheritance. The cys23ser substitution analysis using a suite of methods suggests a plausible effect on the 3D protein structure. The additional cysteine amino acids in human receptors could enable additional structural stability to the protein to aid the modulation of behavioural traits under evolutionary pressure. The results have implications for the role of 5HT2C in the central nervous system (CNS).