HTR2C

HTR2C, or serotonin receptor 2C, is a G protein-coked receptor that binds serotonin (5-HT). The gene is located on the X chromosome (Xq28) and encodes the 5-HT2C receptor, which primarily couples to Gq/11 proteins to activate phospholipase C, generating inositol trisphosphate and diacylglycerol and increasing intracellular calcium. The receptor also exhibits constitutive activity in the absence of ligand.

HTR2C mRNA undergoes RNA editing at five sites (A, B, C, D, E) within the coding region, changing amino acids in the second intracellular loop and C-terminal tail. This editing yields multiple receptor isoforms with distinct signaling properties, generally reducing constitutive activity and G protein coupling in highly edited forms.

HTR2C is broadly expressed in the mammalian brain, with abundant levels in the choroid plexus, prefrontal cortex, limbic regions, hypothalamus, and brainstem. Functionally, 5-HT2C receptors regulate release of dopamine, glutamate, and other neurotransmitters and modulate processes including mood, anxiety, appetite, sleep, and thermoregulation.

Pharmacologically, 5-HT2C receptors are targets of various psychotropic drugs. Antagonism or inverse agonism at 5-HT2C is a feature of several antipsychotics, while selective agonists have been developed for obesity and metabolic disorders. Lorcaserin, a 5-HT2C agonist, was approved for weight management but was withdrawn from the market after concerns about cancer risk. Receptor signaling and editing have been investigated for possible links to mood disorders and obesity.

Genetic variation in HTR2C and altered RNA editing patterns have been explored for associations with psychiatric and metabolic conditions, though findings are not conclusive. Ongoing research examines how editing, splicing, and receptor pharmacology influence CNS function and disease.