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The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein binds the hypothalamic neuropeptides orexin A and orexin B. A related gene (HCRTR1) encodes a G-protein coupled receptor that selectively binds orexin A. [provided by RefSeq, Jan 2009]
HCRTR2 (Hypocretin Receptor 2) is a Protein Coding gene. Diseases associated with HCRTR2 include Cluster Headache and Narcolepsy. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and peptide hormone binding. An important paralog of this gene is HCRTR1.
The OX2 receptors, also known as hypocretin receptor 2, are located primarily in the cerebral cortex, paraventricular hypothalamus, nucleus accumbens, subthalamic and paraventricular thalamus where they are thought to regulate sleep-wakefulness.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH06J055039 | Promoter/Enhancer | 0.9 | EPDnew FANTOM5 ENCODE | 600.2 | -66.1 | -66147 | 0.3 | CEBPB FOS | HSALNG0050745 HCRTR2 ENSG00000224984 piR-33422-366 FAM83B | |
GH06J055112 | Promoter | 0.3 | EPDnew | 600.4 | +6.0 | 6016 | 0.1 | HCRTR2 piR-60885-130 GFRAL | ||
GH06J055106 | Enhancer | 0.3 | Ensembl | 600.7 | +0.5 | 541 | 0.4 | POLR2A | HCRTR2 ENSG00000224984 piR-60885-130 GFRAL | |
GH06J054698 | Enhancer | 0.9 | Ensembl ENCODE | 9.6 | -407.3 | -407259 | 2.8 | BACH1 RELA IKZF2 RCOR1 CTCF DPF2 RELB CTBP1 PKNOX1 ZNF217 | HCRTR2 ENSG00000224984 ENSG00000261116 piR-33614-242 piR-38051-241 lnc-HMGCLL1-4 LOC107986606 FAM83B TINAG | |
GH06J055047 | Enhancer | 0.7 | Ensembl ENCODE | 10.5 | -58.9 | -58859 | 3.2 | ZBTB20 ZNF10 NFE2 OSR2 PKNOX1 CUX1 SPI1 FOXA1 ZNF660 FOS | HCRTR2 ENSG00000224984 HSALNG0050745 piR-50937 FAM83B |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004930 | G protein-coupled receptor activity | IBA | 21873635 |
GO:0008188 | neuropeptide receptor activity | TAS | 9491897 |
GO:0016499 | orexin receptor activity | IBA,IDA | 26950369 |
GO:0017046 | peptide hormone binding | IEA | -- |
GO:0042277 | peptide binding | IBA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005623 | cell | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
GO:0005887 | integral component of plasma membrane | TAS,IDA | 26950369 |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Peptide ligand-binding receptors | ||
2 | Signaling by GPCR | ||
3 | RET signaling | ||
4 | Circadian rythm related genes |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0007165 | signal transduction | IEA | -- |
GO:0007186 | G protein-coupled receptor signaling pathway | TAS | -- |
GO:0007200 | phospholipase C-activating G protein-coupled receptor signaling pathway | IEA | -- |
GO:0007218 | neuropeptide signaling pathway | IEA,IDA | 26950369 |
GO:0007268 | chemical synaptic transmission | TAS | 9491897 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Suvorexant | Approved, Investigational | Pharma | Antagonist, Target, antagonist | 43 | ||
Lemborexant | Approved, Investigational | Pharma | Target, antagonist | 0 | ||
Allopurinol | Approved | Pharma | 176 | |||
Almorexant | Investigational | Pharma | antagonist | OX1R/OX2R antagonist | 0 | |
SB-649868 | Investigational | Pharma | Antagonist, antagonist | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
1-(2,4-dibromo-phenyl)-3-((4S,5S)-2,2-dimethyl-4-phenyl-[1,3]dioxan-5-yl)-urea |
|
Antagonist |
|
|||
ACT-078573 |
|
Antagonist |
|
|||
MK-6096 |
|
Antagonist |
|
|||
N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulphonyl)-amino]-N-pyridin-3-ylmethyl-acetamide |
|
Antagonist |
|
|||
IPSU |
|
1373765-19-5 |
|
|
Compound | Action | Cas Number |
---|---|---|
[Ala11,D-Leu15]-Orexin B | Potent, selective OX2 receptor agonist | 532932-99-3 |
EMPA | Highly potent and selective OX2 antagonist; brain penetrant | 680590-49-2 |
IPSU | OX2 receptor antagonist; orally bioavailable | 1373765-19-5 |
JNJ 10397049 | Selective OX2 receptor antagonist | 708275-58-5 |
TCS OX2 29 | Potent and selective OX2 antagonist | 372523-75-6 |
Compound | Action | Cas Number |
---|---|---|
[Ala11,D-Leu15]-Orexin B | 532932-99-3 | |
Allopurinol | 315-30-0 | |
Almorexant | OX1R/OX2R antagonist | 871224-64-5 |
Almorexant hydrochloride | OX1R/OX2R antagonist | 913358-93-7 |
EMPA | 680590-49-2 | |
JNJ 10397049 | 708275-58-5 | |
Orexin A (human, rat, mouse) | 205640-90-0 | |
Orexin B (human) | 205640-91-1 | |
Orexin B (mouse) | 202801-92-1 | |
OXA (17-33) | 343268-91-7 | |
SB-334867 free base | 792173-99-0 | |
SB408124 | OX(1)receptor antagonist | 288150-92-5 |
TCS 1102 | 916141-36-1 | |
TCS OX2 29 | 372523-75-6 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | HCRTR2 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | HCRTR2 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | HCRTR2 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Hcrtr2 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Hcrtr2 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | HCRTR2 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | HCRTR2 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | HCRTR2 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | hcrtr2 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | hcrtr2 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | NepYr 32 |
|
|
|
SIFR 31 |
|
OneToMany | |||
Worm (Caenorhabditis elegans) |
Secernentea | npr-2 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 06 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
714952 | Likely Benign: not provided | 55,282,411(+) | C/A | MISSENSE_VARIANT | |
728949 | Benign: not provided | 55,282,301(+) | C/T | SYNONYMOUS_VARIANT | |
768101 | Benign: not provided | 55,277,463(+) | G/A | SYNONYMOUS_VARIANT | |
rs2653349 | - | p.Ile308Val | |||
rs41271310 | - | p.Pro10Ser |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
nsv1151776 | CNV | insertion | 26484159 |
Disorder | Aliases | PubMed IDs |
---|---|---|
cluster headache |
|
|
narcolepsy |
|
|
sleep disorder |
|
|
rohhad |
|
|
hematuria, benign familial |
|
|