HRH3 encodes the histamine H3 receptor, a G-protein coupled receptor primarily expressed in the central nervous system that functions as a presynaptic autoreceptor and heteroreceptor 1. The receptor modulates neurotransmitter release from histaminergic, noradrenergic, and other neurons through inhibition of adenylate cyclase and displays high constitutive activity 1. HRH3 demonstrates significant clinical relevance across multiple conditions. In hepatocellular carcinoma, HRH3 is upregulated and promotes tumor growth and metastasis by inducing lamellipodia formation, with expression levels correlating with patient survival outcomes 2. The gene shows altered expression patterns in autism spectrum disorder, where histaminergic gene sets including HRH3 are significantly differentially expressed in postmortem prefrontal cortex tissue 3. Additionally, HRH3 polymorphism rs3787429 associates with chr20 heart failure risk in Chinese populations, with the T allele showing protective effects 4. H3 receptor antagonists show therapeutic promise for alcohol use disorder, reducing drinking behavior and alcohol-induced place preference in rodent models 5. The receptor also appears relevant to stress-related psychiatric conditions, as HRH3 expression is upregulated in prefrontal cortex following chr20 social isolation stress 6.