HCRTR2 (Hypocretin Receptor 2)
A G-protein coupled receptor for orexins, involved in sleep regulation and narcolepsy.
Gene Information Card
| Symbol | HCRTR2 |
|---|---|
| Full Name | Hypocretin Receptor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p12.1 |
| NCBI Gene ID | 3062 ncbi.nlm.nih.gov/gene/3062 |
| Ensembl ID | ENSG00000137252 |
| UniProt ID | O43614 |
| OMIM ID | 602393 |
| HGNC ID | 4849 |
| Aliases | OX2R, orexin receptor 2 |
Description
The HCRTR2 gene encodes the hypocretin (orexin) receptor 2, a G-protein-coupled receptor that binds orexin-A and orexin-B neuropeptides. It is primarily expressed in the brain and plays a critical role in regulating sleep-wake cycles, appetite, and energy homeostasis. Mutations in HCRTR2 are associated with narcolepsy type 2 and other sleep disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Narcolepsy type 2 | Loss-of-function mutations in HCRTR2 impair orexin signaling, leading to excessive daytime sleepiness and disrupted REM sleep. | ClinVar, OMIM |
| Narcolepsy with cataplexy (type 1) | Rare HCRTR2 variants may contribute; however, most cases involve loss of orexin neurons. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Hypothalamus | 20.3 | High |
| Pituitary gland | 8.1 | Low |
| Adrenal gland | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.0 | Neuroblastoma cell line |
| HEK293 | 2.5 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109G>A (p.Gly37Arg) | Missense | <0.01% | Likely loss-of-function; associated with narcolepsy |
| c.124C>T (p.Arg42Cys) | Missense | <0.01% | Reduced receptor activity |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Gly37Arg) reduce orexin binding or signaling, contributing to narcolepsy.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • G-protein coupled receptor activity | • orexin receptor activity |
| • neuropeptide signaling pathway | • positive regulation of calcium ion transport |
| • sleep-wake regulation |
Pathways
• Orexin receptor pathway
• Neuropeptide signaling
• GPCR downstream signaling
Protein Summary
The hypocretin receptor 2 (OX2R) is a 444-amino acid G-protein-coupled receptor with seven transmembrane domains. It is activated by orexin-A and orexin-B, leading to intracellular calcium mobilization and modulation of neuronal excitability. OX2R is essential for maintaining wakefulness and is predominantly expressed in the hypothalamus and brainstem.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HCRTR2 Knockout HEK293 Cell Line | EDJ-KQ4852 | Human | 3062 | Details Get a Quote |
| HCRTR2 Knockout HeLa Cell Line | EDJ-KQ53507 | Human | 3062 | Details Get a Quote |
| HCRTR2 Knockout A-549 Cell Line | EDJ-KQ61976 | Human | 3062 | Details Get a Quote |
| HCRTR2 Knockout HCT 116 Cell Line | EDJ-KQ70458 | Human | 3062 | Details Get a Quote |
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