MTNR1AMTNR1B

The genes *MTNR1A* and *MTNR1B* encode proteins known as melatonin receptor subtypes 1A and 1B, respectively, which are part of the G protein-coupled receptor family. These receptors play a critical role in mediating the physiological effects of melatonin, a hormone primarily secreted by the pineal gland in response to darkness. Melatonin is widely recognized for its role in regulating the sleep-wake cycle, but it also influences other biological processes, including circadian rhythms, seasonal reproduction, and immune function.

*MTNR1A* is located on chromosome 4 (4q35.1) and encodes the melatonin receptor 1A (MTNR1A), which is highly expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus, the brain’s master circadian clock. This receptor is crucial for synchronizing circadian rhythms with environmental light-dark cycles, helping to maintain daily biological rhythms. Variations in *MTNR1A* have been associated with sleep disorders, such as delayed sleep phase syndrome, where individuals experience difficulty falling asleep and waking up at conventional times.

*MTNR1B*, located on chromosome 11 (11q21.2), encodes the melatonin receptor 1B (MTNR1B). Unlike *MTNR1A*, *MTNR1B* is expressed in a broader range of tissues, including the pancreas, where it may influence glucose metabolism. Studies have linked genetic variations in *MTNR1B* to an increased risk of type 2 diabetes, suggesting a potential role in insulin secretion and glucose homeostasis. Additionally, *MTNR1B* expression has been observed in the brain, where it may contribute to mood regulation and other neuroendocrine functions.

Both receptors bind melatonin with high affinity, initiating intracellular signaling pathways that modulate cyclic AMP levels and influence downstream gene expression. While *MTNR1A* is primarily involved in circadian regulation, *MTNR1B* appears to have broader physiological roles, including metabolic and potentially neuropsychiatric functions. Further research is ongoing to fully elucidate the distinct and overlapping functions of these receptors in health and disease.