Property Summary

NCBI Gene PubMed Count 61
PubMed Score 24.90
PubTator Score 71.19

Knowledge Summary

Patent (7,542)

TINX Plot

  Disease (5)

Disease Target Count
Narcolepsy 69
Disease Target Count
Insomnia 20
Disease Target Count Z-score Confidence
Carcinoma 2147 0.0 1.0
Disease Target Count Z-score Confidence
Acquired immunodeficiency syndrome 164 0.0 2.0
Disease Target Count Z-score Confidence
Cannabis dependence 18 3.555 1.8
Heroin dependence 30 3.067 1.5

MLP Assay (2)

AID Type Active / Inconclusive / Inactive Description
624050 confirmatory 25 / 0 / 188 Counterscreen assay for antagonists of the orexin 1 receptor (OX1R; HCRTR1): Fluorescence-based cell-based dose response assay for antagonists of the orexin 2 receptor (OX2R; HCRTR2), run by assay provider
624051 confirmatory 51 / 0 / 162 Counterscreen assay for antagonists of the orexin 1 receptor (OX1R; HCRTR1): Homogeneous Time Resolved Fluorescence (HTRF)-based cell-based dose response assay for antagonists of the orexin 2 receptor (OX2R; HCRTR2), run by assay provider

Gene RIF (47)

PMID Text
26950369 The study determined structures of OX1R bound to the OX1R-selective antagonist SB-674042 and the dual antagonist suvorexant at 2.8-A and 2.75-A resolution and explored mechanisms of antagonist the subtype selectivity between OX1R and OX2R.
26653627 Heart failure patients with minor allele for rs7767652, upstream of hypocretin (orexin) receptor-2 (HCRTR2), were less likely to have improved left ventricular function and a lower prevalence of ejection fraction >35%
26555080 Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation is highly unlikely to be caused by mutations in the exons of the HCRTR2 gene.
26289589 the nonsynonymous rs2653349 single nucleotide polymorphism (SNP) (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with Fagerstrom Test for Nicotine Dependence.
26136476 Antibodies from vaccine-associated narcolepsy sera cross-reacted with both influenza nucleoprotein and hypocretin receptor 2.
25533960 using lipid-mediated crystallization and protein engineering with a novel fusion chimaera, the structure of the human OX2R bound to suvorexant at 2.5 A resolution is solved
25398231 our meta-analysis provides genetic evidence for a role of HCRTR2 in cluster headache
25212464 Decrease in Ox expression with normal human maturation and aging. This may contribute to changes in sleep regulation during development and with aging.
24969517 The genotypic and allelic frequencies of the rs2653349 polymorphism were different between Alzheimer's disease patients and controls. The carriage of the G allele was associated with an increased AD risk.
24599460 Orexinergic innervation and expression of genes encoding OX2R receptor are upregulated in transgenic mice at dusk.
24530395 Both orexin receptor subtypes, OX1R and OX2R, and CB1 cannabinoid receptors are capable of forming constitutive homo- and heteromeric complexes.
24268496 DQ B1 but not HLA-DR typing, TNF-alpha levers, HCRTR1 and HCRTR2 were higher in narcolepsy-cataplexy/schizophrenia patients.
23482607 Expression of the OX2R protein was detected in normal endometrial epithelia, whereas it was frequently lacking in endometrial endometrioid carcinoma.
23034387 [review] Native orexin peptides consist of receptor agonists, orexin-A (33 amino acids) and orexin-B (28 amino acids) (aka hypocretin-1 and hypocretin-2).
22389503 Intramolecular fluorescence resonance energy transfer (FRET) sensors of the orexin OX1 and OX2 receptors identify slow kinetics of agonist activation.
21666548 The Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls, were analyzed.
21510948 Results show that the N-terminal regions of orexin receptor are most important, and the exchange of the area from the C-terminal part of the transmembrane helix 2 to the transmembrane helix 4 is enough to lead to a change of the receptor's ligand profile.
21378163 analysis of orexin receptor 1 and 2 -arrestin-ubiquitin complexes
21186399 both OXA and OXR2 may be involved in the pathogenesis and/or maintenance of BPH.
21071097 Observational study of gene-disease association. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20538960 Observational study of gene-disease association. (HuGE Navigator)
20468064 Observational study of gene-disease association. (HuGE Navigator)
20156195 Data demonstrated that hOX2R expression is regulated by a complex involving a proximal PKA/PKC-regulated promoter and a distal promoter regulating tissue-specific expression of alternative transcripts which in turn regulate receptor levels.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19751316 Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX(2) receptor.
19086053 Observational study of gene-disease association. (HuGE Navigator)
19058789 Observational study of gene-disease association. (HuGE Navigator)
18714784 Both sporadic narcoleptic dogs and human narcolepsy-cataplexy subjects showed a significant decrease in hcrtR1 expression, while declines in hcrtR2 expression were not significant in these cases.
18599270 This study describes the intracellular signalling pathways involved in OX2R-mediated ERK(1/2) and p38 MAPK activation.
18399985 Three new polymorphisms of the HCRTR2 gene are significantly associated with cluster headache.
18399985 Observational study of gene-disease association. (HuGE Navigator)
17883525 Observational study of gene-disease association. (HuGE Navigator)
17883525 This study does not support a major contribution of the HCRTR2 G1246A polymorphism to the pathogenesis of migraine in contrast to its effects in cluster headache.
17645762 Observational study of gene-disease association. (HuGE Navigator)
17645762 the HCRTR2 gene is not a genetic risk factor in migraine.
17563843 Observational study of gene-disease association. (HuGE Navigator)
17563843 polymorphism of the HCRTR2 gene may modulate the genetic risk for cluster headache
17376114 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17376114 Our results do not support a role of the HCRTR2 G1246A polymorphism in drug responses in CH.
16554494 Observational study of gene-disease association. (HuGE Navigator)
15978554 Observational study of gene-disease association. (HuGE Navigator)
15797953 All adrenal cortex adenomas expressed OX1-R and OX2-R mRNAs, and real-time PCR showed that the expression of both receptors was up-regulated in adenomas
15477554 Observational study of gene-disease association. (HuGE Navigator)
15477554 The data suggest that the HCRTR2 gene or a linked locus significantly modulates the risk for cluster headache.
15274044 Observational study of gene-disease association. (HuGE Navigator)
15070969 both OX1R and OX2R are expressed in the testis, epididymis, penis, and seminal vesicle

AA Sequence

MSGTKLEDSPPCRNWSSASELNETQEPFLNPTDYDDEEFLRYLWREYLHPKEYEWVLIAGYIIVFVVALI      1 - 70
GNVLVCVAVWKNHHMRTVTNYFIVNLSLADVLVTITCLPATLVVDITETWFFGQSLCKVIPYLQTVSVSV     71 - 140
SVLTLSCIALDRWYAICHPLMFKSTAKRARNSIVIIWIVSCIIMIPQAIVMECSTVFPGLANKTTLFTVC    141 - 210
DERWGGEIYPKMYHICFFLVTYMAPLCLMVLAYLQIFRKLWCRQIPGTSSVVQRKWKPLQPVSQPRGPGQ    211 - 280
PTKSRMSAVAAEIKQIRARRKTARMLMIVLLVFAICYLPISILNVLKRVFGMFAHTEDRETVYAWFTFSH    281 - 350
WLVYANSAANPIIYNFLSGKFREEFKAAFSCCCLGVHHRQEDRLTRGRTSTESRKSLTTQISNFDNISKL    351 - 420
SEQVVLTSISTLPAANGAGPLQNW                                                  421 - 444
//

Text Mined References (62)

PMID Year Title
26950369 2016 Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptors.
26653627 2015 Systems Genomics Identifies a Key Role for Hypocretin/Orexin Receptor-2 in Human Heart Failure.
26555080 2016 Absence of mutations in HCRT, HCRTR1 and HCRTR2 in patients with ROHHAD.
26289589 2015 Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies.
26136476 2015 Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2.
25533960 2015 Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant.
25398231 2015 Cluster headache and the hypocretin receptor 2 reconsidered: a genetic association study and meta-analysis.
25231870 2014 Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
25212464 2015 Changes in orexin (hypocretin) neuronal expression with normal aging in the human hypothalamus.
24969517 2014 Is HCRTR2 a genetic risk factor for Alzheimer's disease?
24599460 2014 Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock.
24530395 2014 Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors.
24268496 2014 Narcolepsy-cataplexy and schizophrenia in adolescents.
23482607 2013 Expression of type 2 orexin receptor in human endometrium and its epigenetic silencing in endometrial cancer.
23034387 2013 Physiology of the orexinergic/hypocretinergic system: a revisit in 2012.
22389503 2012 Intramolecular fluorescence resonance energy transfer (FRET) sensors of the orexin OX1 and OX2 receptors identify slow kinetics of agonist activation.
21666548 2011 Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene.
21510948 2011 Orexin/hypocretin receptor chimaeras reveal structural features important for orexin peptide distinction.
21378163 2011 Temporal profiling of orexin receptor-arrestin-ubiquitin complexes reveals differences between receptor subtypes.
21186399 2011 Elevated expression of orexin receptor 2 (HCRTR2) in benign prostatic hyperplasia is accompanied by lowered serum orexin A concentrations.
21071097 2011 Association between major mood disorders and the hypocretin receptor 1 gene.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20538960 2010 A candidate gene study of obstructive sleep apnea in European Americans and African Americans.
20468064 2010 Association study of 182 candidate genes in anorexia nervosa.
20156195 2010 Genomic organization and regulation of the human orexin (hypocretin) receptor 2 gene: identification of alternative promoters.
20041166 2009 Common genetic variation and the control of HIV-1 in humans.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19751316 2009 Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX(2) receptor.
19086053 2009 Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.
19058789 2009 A common variant in DRD3 receptor is associated with autism spectrum disorder.
18714784 2008 Hypocretin receptor expression in canine and murine narcolepsy models and in hypocretin-ligand deficient human narcolepsy.
18599270 2008 The signalling profile of recombinant human orexin-2 receptor.
18399985 2008 Haplotype analysis confirms the association between the HCRTR2 gene and cluster headache.
17883525 2007 Association between migraine and the G1246A polymorphism in the hypocretin receptor 2 gene.
17645762 2007 The 1246G-->A polymorphism of the HCRTR2 gene is not associated with migraine.
17563843 2007 Association between the G1246A polymorphism of the hypocretin receptor 2 gene and cluster headache: a meta-analysis.
17376114 2007 The G1246A polymorphism in the hypocretin receptor 2 gene is not associated with treatment response in cluster headache.
16754659 2006 Stable association between G alpha(q) and phospholipase C beta 1 in living cells.
16554494 2006 Cluster headache is associated with the G1246A polymorphism in the hypocretin receptor 2 gene.
15978554 2005 Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects.
15797953 2005 Preproorexin and orexin receptors are expressed in cortisol-secreting adrenocortical adenomas, and orexins stimulate in vitro cortisol secretion and growth of tumor cells.
15477554 2004 A polymorphism of the hypocretin receptor 2 gene is associated with cluster headache.
15274044 2004 Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity.
15070969 2004 Expression of human prepro-orexin and signaling characteristics of orexin receptors in the male reproductive system.
14574404 2003 The DNA sequence and analysis of human chromosome 6.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11830291 2002 Cellular localization of orexin receptors in human adrenal gland, adrenocortical adenomas and pheochromocytomas.
11723285 2001 Polymorphisms in hypocretin/orexin pathway genes and narcolepsy.
11600545 2001 Expression of orexin-A and functional orexin type 2 receptors in the human adult adrenals: implications for adrenal function and energy homeostasis.
11549701 2001 Expression and coupling characteristics of the CRH and orexin type 2 receptors in human fetal adrenals.
11443222 2001 Cellular localization of orexin receptors in human pituitary.
11340621 2001 Hypocretin/orexin, sleep and narcolepsy.
11297593 2001 Cellular localization of orexin receptors in human pituitary.
11283317 2001 To eat or to sleep? Orexin in the regulation of feeding and wakefulness.
11158046 2001 Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade.
11076863 2000 DNA cloning using in vitro site-specific recombination.
10981966 2000 Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function.
10973318 2000 A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains.
9527442 1998 Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.
9491897 1998 Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.
9491885 1998 Obesity and the hypothalamus: novel peptides for new pathways.
9419374 1998 The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.