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] See more...

Aliases for HCRTR2 Gene

Aliases for HCRTR2 Gene

  • Hypocretin Receptor 2 2 3 5
  • Hypocretin (Orexin) Receptor 2 2 3
  • Hypocretin Receptor Type 2 3 4
  • Orexin Receptor Type 2 3 4
  • OX2R 2 3
  • Orexin Type-2 Receptor 3
  • Orexin Receptor 2 2
  • HCRTR2 5
  • Ox-2-R 4
  • Ox2-R 4
  • Ox2R 4

External Ids for HCRTR2 Gene

Previous GeneCards Identifiers for HCRTR2 Gene

  • GC06P055041
  • GC06P055085
  • GC06P055147
  • GC06P054873

Summaries for HCRTR2 Gene

Entrez Gene Summary for HCRTR2 Gene

  • 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]

GeneCards Summary for HCRTR2 Gene

HCRTR2 (Hypocretin Receptor 2) is a Protein Coding gene. Diseases associated with HCRTR2 include Cluster Headache and Narcolepsy. Among its related pathways are Peptide ligand-binding receptors 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.

UniProtKB/Swiss-Prot Summary for HCRTR2 Gene

  • Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides (PubMed:9491897, PubMed:26950369). Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding (PubMed:9491897, PubMed:26950369).

Tocris Summary for HCRTR2 Gene

  • 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.

Gene Wiki entry for HCRTR2 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HCRTR2 Gene

Genomics for HCRTR2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HCRTR2 Gene
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 250.2 -66.1 -66147 0.3 FOS CEBPB HSALNG0050745-001 HSALNG0050745-002 HCRTR2 ENSG00000224984 HSALNG0050744 FAM83B
GH06J055112 Promoter 0.3 EPDnew 250.4 +6.0 6016 0.1 HCRTR2 piR-60885-130 GFRAL
GH06J055106 Enhancer 0.3 Ensembl 255.6 +0.2 241 1 POLR2A HCRTR2 ENSG00000224984 piR-60885-130 GFRAL
GH06J054698 Enhancer 0.9 Ensembl ENCODE 9.6 -407.3 -407259 2.8 ZNF217 NR2C1 CTBP1 BHLHE40 CTCF SMARCE1 PKNOX1 ELF1 FOXA1 IKZF1 HCRTR2 ENSG00000224984 ENSG00000261116 HSALNG0050733 piR-33614-242 HSALNG0050731-001 LOC107986606 lnc-HMGCLL1-4 HSALNG0050731-002 FAM83B
GH06J055047 Enhancer 0.8 Ensembl ENCODE 10.5 -58.9 -58859 3.2 ZNF10 CUX1 NFE2 JUND SPI1 PKNOX1 FOXA1 ZNF660 OSR2 FOS HCRTR2 ENSG00000224984 HSALNG0050745-001 HSALNG0050745-002 HSALNG0050745-003 FAM83B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HCRTR2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HCRTR2

Top Transcription factor binding sites by QIAGEN in the HCRTR2 gene promoter:
  • aMEF-2
  • c-Myb
  • Cart-1
  • FOXI1
  • HFH-3
  • MEF-2
  • SEF-1 (1)
  • SRF
  • SRF (504 AA)
  • SRY

Genomic Locations for HCRTR2 Gene

Latest Assembly
chr6:55,106,460-55,284,698
(GRCh38/hg38)
Size:
178,239 bases
Orientation:
Plus strand

Previous Assembly
chr6:54,971,267-55,147,415
(GRCh37/hg19 by Entrez Gene)
Size:
176,149 bases
Orientation:
Plus strand

chr6:55,039,050-55,147,418
(GRCh37/hg19 by Ensembl)
Size:
108,369 bases
Orientation:
Plus strand

Genomic View for HCRTR2 Gene

Genes around HCRTR2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HCRTR2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HCRTR2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HCRTR2 Gene

Proteins for HCRTR2 Gene

  • Protein details for HCRTR2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43614-OX2R_HUMAN
    Recommended name:
    Orexin receptor type 2
    Protein Accession:
    O43614
    Secondary Accessions:
    • Q5VTM0

    Protein attributes for HCRTR2 Gene

    Size:
    444 amino acids
    Molecular mass:
    50694 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for HCRTR2 Gene

neXtProt entry for HCRTR2 Gene

Post-translational modifications for HCRTR2 Gene

  • Glycosylation at Asn14, Asn22, and Asn202
  • Modification sites at PhosphoSitePlus

Other Protein References for HCRTR2 Gene

No data available for DME Specific Peptides for HCRTR2 Gene

Domains & Families for HCRTR2 Gene

Gene Families for HCRTR2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • FDA approved drug targets
  • G-protein coupled receptors
  • Predicted membrane proteins

Protein Domains for HCRTR2 Gene

InterPro:
Blocks:
  • Orexin receptor signature

Suggested Antigen Peptide Sequences for HCRTR2 Gene

GenScript: Design optimal peptide antigens:
  • Hypocretin receptor type 2 (OX2R_HUMAN)
  • cDNA, FLJ95033, Homo sapiens hypocretin (orexin) receptor 2 (HCRTR2), mRNA (Q548Y0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O43614

UniProtKB/Swiss-Prot:

OX2R_HUMAN :
  • The N-terminal region is required for orexin signaling.
  • Belongs to the G-protein coupled receptor 1 family.
Domain:
  • The N-terminal region is required for orexin signaling.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with HCRTR2: view

Function for HCRTR2 Gene

Molecular function for HCRTR2 Gene

UniProtKB/Swiss-Prot Function:
Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides (PubMed:9491897, PubMed:26950369). Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding (PubMed:9491897, PubMed:26950369).
GENATLAS Biochemistry:
hypocretin receptor 2,G protein coupled receptor superfamily binding both HCRT isoforms A and B

Phenotypes From GWAS Catalog for HCRTR2 Gene

Gene Ontology (GO) - Molecular Function for HCRTR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G protein-coupled receptor activity IBA 21873635
GO:0005515 protein binding IPI 32814053
GO:0008188 neuropeptide receptor activity TAS 9491897
GO:0016499 orexin receptor activity IBA,IDA 26950369
GO:0017046 peptide hormone binding IEA --
genes like me logo Genes that share ontologies with HCRTR2: view
genes like me logo Genes that share phenotypes with HCRTR2: view

Animal Models for HCRTR2 Gene

MGI Knock Outs for HCRTR2:

miRNA for HCRTR2 Gene

miRTarBase miRNAs that target HCRTR2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HCRTR2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HCRTR2 Gene

Localization for HCRTR2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HCRTR2 Gene

Cell membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HCRTR2 gene
Compartment Confidence
plasma membrane 5
nucleus 2
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
cytosol 1

Gene Ontology (GO) - Cellular Components for HCRTR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
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 --
GO:0045202 synapse IEA --
genes like me logo Genes that share ontologies with HCRTR2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HCRTR2 Gene

Pathways & Interactions for HCRTR2 Gene

genes like me logo Genes that share pathways with HCRTR2: view

SIGNOR curated interactions for HCRTR2 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for HCRTR2 Gene

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
genes like me logo Genes that share ontologies with HCRTR2: view

Drugs & Compounds for HCRTR2 Gene

(32) Drugs for HCRTR2 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Suvorexant Approved, Investigational Pharma Antagonist, Target 46
Lemborexant Approved, Investigational Pharma Target, antagonist 0
Allopurinol Approved Pharma 182
Almorexant Investigational Pharma antagonist OX1R/OX2R antagonist 0
SB-649868 Investigational Pharma Antagonist 0

(7) Additional Compounds for HCRTR2 Gene - From: IUPHAR, Novoseek, and Tocris

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

(5) Tocris Compounds for HCRTR2 Gene

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

(14) ApexBio Compounds for HCRTR2 Gene

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
genes like me logo Genes that share compounds with HCRTR2: view

Drug products for research

Transcripts for HCRTR2 Gene

mRNA/cDNA for HCRTR2 Gene

2 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HCRTR2

Alternative Splicing Database (ASD) splice patterns (SP) for HCRTR2 Gene

No ASD Table

Relevant External Links for HCRTR2 Gene

GeneLoc Exon Structure for
HCRTR2

Expression for HCRTR2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HCRTR2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HCRTR2 Gene

This gene is overexpressed in Brain - Hypothalamus (x9.4), Brain - Substantia nigra (x5.6), and Brain - Anterior cingulate cortex (BA24) (x4.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HCRTR2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HCRTR2

SOURCE GeneReport for Unigene cluster for HCRTR2 Gene:

Hs.151624

Evidence on tissue expression from TISSUES for HCRTR2 Gene

  • Nervous system(2.4)
genes like me logo Genes that share expression patterns with HCRTR2: view

Primer products for research

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for HCRTR2 Gene

Orthologs for HCRTR2 Gene

This gene was present in the common ancestor of animals.

Orthologs for HCRTR2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HCRTR2 29 30
  • 99.55 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia HCRTR2 29 30
  • 93.09 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HCRTR2 29 30
  • 89.86 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hcrtr2 29
  • 88.04 (n)
Mouse
(Mus musculus)
Mammalia Hcrtr2 29 16 30
  • 87.96 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia HCRTR2 30
  • 84 (a)
OneToOne
Chicken
(Gallus gallus)
Aves HCRTR2 29 30
  • 80.2 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia HCRTR2 30
  • 81 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hcrtr2 29
  • 75.09 (n)
Zebrafish
(Danio rerio)
Actinopterygii hcrtr2 29 30
  • 68.88 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta NepYr 31
  • 31 (a)
SIFR 30
  • 17 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea npr-2 29
  • 42.7 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 35 (a)
OneToMany
Species where no ortholog for HCRTR2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for HCRTR2 Gene

ENSEMBL:
Gene Tree for HCRTR2 (if available)
TreeFam:
Gene Tree for HCRTR2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HCRTR2: view image
Alliance of Genome Resources:
Additional Orthologs for HCRTR2

Paralogs for HCRTR2 Gene

(16) SIMAP similar genes for HCRTR2 Gene using alignment to 4 proteins:

  • OX2R_HUMAN
  • Q548Y0_HUMAN
  • S4WX84_HUMAN
  • S4X0W3_HUMAN
genes like me logo Genes that share paralogs with HCRTR2: view

Variants for HCRTR2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HCRTR2 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
rs12111299 Benign: not provided 55,277,463(+) G/A
NM_001526.4(HCRTR2):c.846G>A (p.Thr282=)
SYNONYMOUS
rs141299250 Likely Benign: not provided 55,282,411(+) C/A
NM_001526.4(HCRTR2):c.1292C>A (p.Thr431Lys)
MISSENSE
rs146725330 Benign: not provided 55,282,301(+) C/T
NM_001526.4(HCRTR2):c.1182C>T (p.Leu394=)
SYNONYMOUS
rs2653349 -- p.Ile308Val
rs41271310 -- p.Pro10Ser

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HCRTR2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for HCRTR2 Gene

Variant ID Type Subtype PubMed ID
nsv1151776 CNV insertion 26484159

Variation tolerance for HCRTR2 Gene

Residual Variation Intolerance Score: 65.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.24; 40.23% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HCRTR2 Gene

Human Gene Mutation Database (HGMD)
HCRTR2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HCRTR2
Leiden Open Variation Database (LOVD)
HCRTR2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HCRTR2 Gene

Disorders for HCRTR2 Gene

MalaCards: The human disease database

(12) MalaCards diseases for HCRTR2 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
cluster headache
narcolepsy
  • narcolepsy, without cataplexy
sleep disorder
  • non-organic sleep disorder
rohhad
  • rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation
hematuria, benign familial
  • bfh
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for HCRTR2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HCRTR2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HCRTR2 Gene

Publications for HCRTR2 Gene

  1. Haplotype analysis confirms the association between the HCRTR2 gene and cluster headache. (PMID: 18399985) Rainero I … Pinessi L (Headache 2008) 3 22 40
  2. The G1246A polymorphism in the hypocretin receptor 2 gene is not associated with treatment response in cluster headache. (PMID: 17376114) Schürks M … Rosskopf D (Cephalalgia : an international journal of headache 2007) 3 22 40
  3. The 1246G-->A polymorphism of the HCRTR2 gene is not associated with migraine. (PMID: 17645762) Pinessi L … Vaula G (Cephalalgia : an international journal of headache 2007) 3 22 40
  4. Association between migraine and the G1246A polymorphism in the hypocretin receptor 2 gene. (PMID: 17883525) Schürks M … Rosskopf D (Headache 2007) 3 22 40
  5. Association between the G1246A polymorphism of the hypocretin receptor 2 gene and cluster headache: a meta-analysis. (PMID: 17563843) Rainero I … Pinessi L (The journal of headache and pain 2007) 3 22 40

Products for HCRTR2 Gene

Sources for HCRTR2 Gene