HCRTR1 (Hypocretin Receptor 1): Genetics, Function, and Clinical Significance
A comprehensive biomedical overview of the HCRTR1 gene, encoding the hypocretin receptor 1, with focus on its role in sleep regulation, neurological disorders, and potential therapeutic targeting.
Gene Information Card
| Symbol | HCRTR1 |
|---|---|
| Full Name | Hypocretin receptor 1 |
| Gene Type | protein coding |
| Chromosomal Location | 1p35.2 |
| NCBI Gene ID | 3961 ncbi.nlm.nih.gov/gene/3961 |
| Ensembl ID | ENSG00000121764 |
| UniProt ID | O43613 |
| OMIM ID | 602392 |
| HGNC ID | 4848 |
| Aliases | OX1R, OX1R1, HCRTR1 |
Description
The HCRTR1 gene encodes hypocretin receptor 1 (also known as orexin receptor 1, OX1R), a G-protein coupled receptor that binds the neuropeptides hypocretin/orexin-A and -B. It is predominantly expressed in the brain, particularly in the hypothalamus, and plays a critical role in regulating sleep-wake cycles, arousal, feeding behavior, and energy homeostasis. Dysregulation of HCRTR1 signaling has been implicated in narcolepsy, depression, and substance abuse. The receptor is a target for therapeutic interventions in sleep and psychiatric disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Narcolepsy | Loss of hypocretin signaling due to reduced HCRTR1 function or ligand deficiency leads to disrupted sleep-wake regulation. | ClinVar, OMIM |
| Depression | Altered HCRTR1 expression or signaling may contribute to mood dysregulation; antagonists are being explored as antidepressants. | PubMed, OMIM |
| Substance Use Disorders | HCRTR1 modulates reward pathways; antagonists may reduce drug-seeking behavior. | PubMed, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | High |
| Adrenal Gland | 2.1 | Low |
| Testis | 1.5 | Low |
| Lung | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 5.2 | Neuroblastoma cell line; moderate expression |
| U87-MG | 3.4 | Glioblastoma cell line; low expression |
| HEK293 | 0.5 | Embryonic kidney; very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.275C>T (p.Pro92Leu) | Missense | 0.01% | Potential loss of function; associated with narcolepsy in rare cases |
| c.124G>A (p.Val42Met) | Missense | 0.005% | Uncertain significance; may affect receptor signaling |
| c.1027A>G (p.Ile343Val) | Missense | 0.02% | Benign polymorphism; no known clinical effect |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair receptor binding or signal transduction, leading to reduced hypocretin signaling, potentially contributing to narcolepsy or other sleep disorders.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; such mutations could theoretically enhance signaling but are not documented in current databases.
Dominant Negative (DN)
No evidence of dominant-negative effects for HCRTR1 mutations; receptor functions as a monomer, and haploinsufficiency is not established.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • neuropeptide binding |
| • orexin receptor activity | • plasma membrane |
| • signal transduction | • G protein-coupled receptor signaling pathway |
| • regulation of sleep-wake cycle | • feeding behavior |
Pathways
• Orexin receptor signaling pathway
• Neuroactive ligand-receptor interaction
• GPCR downstream signaling
• Circadian entrainment
Protein Summary
Hypocretin receptor 1 (OX1R) is a 425-amino acid G-protein coupled receptor with seven transmembrane domains. It is encoded by HCRTR1 and primarily couples to Gq/11 proteins, activating phospholipase C and increasing intracellular calcium. The receptor is activated by orexin-A with higher affinity than orexin-B. It is expressed in the brain, especially in the locus coeruleus, hippocampus, and hypothalamus, where it modulates arousal, wakefulness, and reward. Structural studies have revealed the binding pocket for orexin peptides and small-molecule antagonists, aiding drug design.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HCRTR1 Knockout HEK293 Cell Line | EDJ-KQ4851 | Human | 3061 | Details Get a Quote |
| HCRTR1 Knockout HeLa Cell Line | EDJ-KQ53506 | Human | 3061 | Details Get a Quote |
| HCRTR1 Knockout A-549 Cell Line | EDJ-KQ61975 | Human | 3061 | Details Get a Quote |
| HCRTR1 Knockout HCT 116 Cell Line | EDJ-KQ70457 | Human | 3061 | Details Get a Quote |
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