HCRT Gene - Hypocretin Neuropeptide Precursor: Function, Mutations, and Narcolepsy

The HCRT gene encodes the preprohypocretin precursor, which is cleaved into two neuropeptides: hypocretin-1 (orexin-A) and hypocretin-2 (orexin-B). These peptides bind to G-protein-coupled receptors (HCRTR1 and HCRTR2) to regulate wakefulness, appetite, and energy homeostasis. Loss of HCRT-producing neurons or mutations in HCRT cause narcolepsy type 1, characterized by excessive daytime sleepiness and cataplexy.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Hypocretin receptor signaling (HCRTR1/HCRTR2)

• Neuroactive ligand-receptor interaction (KEGG:04080)

• Orexin receptor pathway (Reactome: R-HSA-388841)

The HCRT gene encodes preprohypocretin, a 131-amino-acid precursor that is proteolytically cleaved to produce two neuropeptides: hypocretin-1 (orexin-A, 33 aa) and hypocretin-2 (orexin-B, 28 aa). These peptides are produced exclusively in the lateral hypothalamus and bind to two G-protein-coupled receptors (HCRTR1 and HCRTR2) to promote wakefulness, stimulate appetite, and regulate energy balance. Deficiency of hypocretin is the primary cause of narcolepsy type 1.