OPRM1Gen

OPRM1Gen is a gene that encodes the mu-opioid receptor, a member of the opioid receptor family. In humans, the gene is commonly referred to as OPRM1 and is located on chromosome 6. The gene produces multiple transcript variants through alternative splicing, yielding receptors with tissue-specific expression patterns.

The mu-opioid receptor is a G protein-coupled receptor with seven transmembrane domains. It binds endogenous opioid peptides such as beta-endorphin and enkephalins, as well as exogenous opioids including morphine and fentanyl. Activation inhibits adenylyl cyclase, reduces cAMP, opens potassium channels, and decreases voltage-gated calcium entry, leading to decreased neuronal excitability and neurotransmitter release.

Expression is highest in brain regions involved in pain processing and reward, such as the spinal cord, periaqueductal gray, caudate nucleus, and nucleus accumbens, as well as in some peripheral tissues.

Genetic variation in OPRM1Gen influences receptor function and pharmacology. The best-studied variant is A118G (rs1799971), which changes an amino acid in the receptor and has been associated with altered opioid analgesic requirements and risk of opioid use disorder in some populations; results across studies are heterogeneous. Other promoter or splice-site variants have been described but with less-consistent effects.

In clinical research, OPRM1Gen is examined for pharmacogenomic applications, including tailoring opioid dosing and predicting response to treatments for addiction or alcohol use disorders, as well as investigating its role in mood and stress-related disorders.

OPRM1Gen is conserved across mammals, with mouse and rat orthologs used in functional studies. Comparative analyses help elucidate receptor signaling mechanisms and the consequences of genetic variation on behavior and drug response.