Property Summary

NCBI Gene PubMed Count 79
PubMed Score 254.04
PubTator Score 146.58

Knowledge Summary

Patent (21,522)

Expression

  Differential Expression (4)

Disease log2 FC p
uncontrolled asthma 1.400 3.5e-02
osteosarcoma -1.150 3.1e-05
medulloblastoma, large-cell 1.400 5.1e-04
non primary Sjogren syndrome sicca -1.300 1.8e-02

MLP Assay (2)

AID Type Active / Inconclusive / Inactive Description
434974 screening 0 / 0 / 0 Late-stage radioligand binding assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen
504381 other 0 / 0 / 0 Late-stage radioligand binding assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen Set 2

Gene RIF (69)

PMID Text
26828993 Activation of the H4R could induce phosphorylation of ERK.
26823878 Suggest roles for HRH4 polymorphisms and ankylosing spondylitis susceptibility.
25300787 Functional H4 receptors increasing (35)S-GTPgammaS binding and/or decreasing noradrenaline release are not found in human, guinea pig or mouse cortex
25293806 HRH4 was increased in clinically-isolated syndrome and different stages of multiple sclerosis compared to health control.
25273276 No evidence was found for the presence of histamine H4 receptor in monocytes.
25098339 Molecular modelling studies, including molecular dynamic simulations and calculation of Gibbs energy of solvation of hH3R and hH4R, were studied.
24934979 The activation of H4R in human mast cells produced not only inflammatory mediators that are associated with allergic reactions but also other inflammatory conditions.
24799603 In neutrophils, the H4 receptor may block signals emanating from Mac-1-controlling degranulation. Engagement of the H4 receptor by selective agonists blocked Mac-1-dependent activation of p38 MAPK.
24787705 H4 receptor expression plays a role in pathological vessel leakage associated with choroidal neovascularization
24530738 The inhibitory effects of histamine on reactive oxygen species production in whole blood phagocytes are caused by H2R rather than H4R histamine receptors.
24493592 Methyl substitution in histamine homologs offers a way to shift the selectivity in favor of the H4R.
24447834 Data show down-regulation of cyclic adenosine monophosphate (cAMP) was the secondary signalling after H4 receptor activation, which in turn resulting in inactivation of transforming growth factor-beta1(TGF-beta1) pathway.
24432340 Obtained results allow for statement that developed cellular model may be successfully employed in search for new compounds active at histamine H4 receptor
24372819 Increased expression of the H4 receptor was observed in HaCaT cells following differentiation.
24236486 But carriers of one or three copies of HRH1 (5% of individuals), HRH2 (1.1%) and HRH4 genes (0.9%) were also identified.
23932072 H4R is highly expressed on keratinocytes from patients with atopic dermatitis, and its stimulation induces keratinocyte proliferation.
23677734 In this review, we focus on the role of histamine and its receptors in the treatment of Alzheimer's disease.
23517361 Copy number variationss of the HRH4 gene are associated with atopic dermatitis in a Chinese population.
23481304 Genotypes of HRH4 gene are signi fi cantly associated with the risk and malignant degree of breast cancer in Chinese Han populations.
23425150 Histamine through the histamine H4 receptor exhibits a crucial role in breast tumour progression.
22973061 The efficacy of 31 known hHR ligands to induce Galpha(i) protein signaling and beta-arrestin2 recruitment by the hHR.
22885137 study identified novel functional properties in terms of voltage sensitivities and deactivation rates, which differed between the histamine hH3445, hH3365, and H4 receptors
22653292 Twenty-one SNPs of the HRH4 gene were genotyped in 313 asthmatic patients and 360 controls. Genotype distribution of three SNPs rs17187619, rs527790 and rs487202 differed significantly between patients with or without infection-induced asthma.
22363581 Deletion of HRH4 gene is present in gastric cancer cases and is closely correlated with attenuated gene expression.
22201741 fundamental concepts of HR structure modeling and its implementation in drug discovery (review)
22153663 analysis of fragment optimization and analysis of binding kinetics for ligand based design of novel histamine H receptor antagonists
22118942 Histamine receptor-4-mRNA expression showed a significant increase in caudate nucleus and putamen in Parkinson's disease patients.
21881994 Report down-regulation of HRH4 mRNA in synovial tissue from rheumatoid arthritis patients compared to those with osteoarthritis.
21741967 histamine H(4) receptor as an attractive target in the treatment of inflammatory and autoimmune disorders
21614010 our results indicate that the H(4)R is highly expressed on plasmacytoid dendritic cells in psoriasis and influences cytokine production and migration of these cells
21609450 These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs
21171298 Histamine H4 receptors were found in normal nasal mucosa, and increased significantly in nasal mucosa of allergic rhinitis patients.
21104170 we describe a possible genetic impact on the expression level of the histamine H4 receptor and summarize the current data regarding the activity of the histamine H4 receptor on the key effector cells in atopic dermatitis
20800603 Observational study of gene-disease association. (HuGE Navigator)
20722760 slan-dendritic cells (slanDC) express the H(4) R and its stimulation leads to reduced pro-inflammatory capacity of slanDC
20618322 Copy number variations of the human histamine H4 receptor gene are associated with systemic lupus erythematosus
20618322 Observational study of gene-disease association. (HuGE Navigator)
20237496 Observational study of gene-disease association. (HuGE Navigator)
20199554 Polymorphisms of ss142022671, ss142022677 and ss142022679 in HRH4 are associated with atopic dermatitis.
20199554 Observational study of gene-disease association. (HuGE Navigator)
20192225 Data reveal that the sulfonamide analogues have excellent H(4)R affinity and behave as inverse agonists at the human H(4)R.
19958313 Langerhans cells express a functional H(4)R and point towards a possible pathogenic relevance of the H(4)R in inflammatory and allergic diseases.
19662098 show that progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid formation
19281909 Human CD4(+) T cells express a functional H(4)R. The receptor is upregulated under T(H)2 conditions, and its stimulation leads to induction of AP-1 and IL-31.
19271148 Data describe the ultrastructure of the choroid plexus, the number of mast cells that may infiltrate it, and the immunodistribution of histamine receptors H4 and histamine-releasing factor.
19166345 hH(4)R shows high constitutive activity and structural instability and hH(4)R shows a G-protein-independent high-affinity state.
19156168 Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19053770 analysis of how quinazolines can act as histamine H4 receptor inverse agonists
19046950 findings show that transcripts of H(4) receptor are present in all analyzed regions of the central nervous system, including spinal cord, hippocampus, cortex, thalamus & amygdala, with the highest levels of H(4) mRNA detected in the spinal cord
18635748 Phenylalanine 169 in the second extracellular loop of the human histamine H4 receptor is responsible for the difference in agonist binding between human and mouse H4 receptors.
18582456 GIRK channels represent a novel effector system for histamine H(4) receptor modulation
18572901 Molecular dynamics (MD) simulations in a membrane-embedded environment were carried out on the homology model of the human histamine H4 receptor
18452403 Recombinant histamine 4 receptor (H4R) splice variants derived from cord blood cells have a dominant negative effect on functionality, as these H4R are retained intracellularly and inactivate a population of H4R, presumably via hetero-oligomerization.
18345506 Data show that histamine regulates pancreatic carcinoma cell growth through H3 and H4 receptors.
18345495 Data suggest that histamine receptor H4R-selective ligands influence the STAT6 transcription activation domain and DNA-binding.
18345487 Results describe the expression of the histamine H4 receptor in human synovial cells.
18258331 a dramatic alteration in the distribution of histamine receptors in colon cancer
18239617 Inflammatory dendritic epidermal cells express a functionally active H(4)R, which upon stimulation leads to downregulation of CCL2 and IL-12.
17978505 Expression of histamine H4 receptor in synovial cells from rheumatoid arthritis patients is reported.
17806182 Results describe the distribution pattern of histamine H4 receptor in human synovial tissue in patients with rheumaoid arthritis.
17806168 Results describe the expression of histamine H4 receptors in normal placentas and in placentas from pregnancies complicated by pregestational diabetes.
17681365 H4 histamine receptor mediates optimal migration of mast cell precursors to CXCL12 and plays a role in the perpetuation of allergic response.
17627982 Histamine excites human enteric neurones and this effect involves histamine H1-4 receptors.
17507084 The H(4)R could represent an important anti-inflammatory receptor on monocytes and could be an interesting target for drug development.
16547812 STAT6 binding to STAT6 promotor gene was regulated by H4 receptor-induced signal transduction and/or cross talk particularly in atopic human lymphocytes ex vivo
16547802 results showed for the first time the presence of histamine h4 receptor protein in epithelial cells of human normal mammary gland
16203768 histamine exerts both a proproliferative and a proangiogenic effect via H2/H4 receptor activation, mediated by increasing COX-2-related PGE2 production in COX-2-expressing colon cancer cells
15265943 Human eosinophils express H4. CCL16 is a novel functional ligand for H4, and it induced efficient migratory responses in human eosinophils.
15191551 human mast cells constitutively express primarily H2 and H4 receptors

AA Sequence

MPDTNSTINLSLSTRVTLAFFMSLVAFAIMLGNALVILAFVVDKNLRHRSSYFFLNLAISDFFVGVISIP      1 - 70
LYIPHTLFEWDFGKEICVFWLTTDYLLCTASVYNIVLISYDRYLSVSNAVSYRTQHTGVLKIVTLMVAVW     71 - 140
VLAFLVNGPMILVSESWKDEGSECEPGFFSEWYILAITSFLEFVIPVILVAYFNMNIYWSLWKRDHLSRC    141 - 210
QSHPGLTAVSSNICGHSFRGRLSSRRSLSASTEVPASFHSERQRRKSSLMFSSRTKMNSNTIASKMGSFS    211 - 280
QSDSVALHQREHVELLRARRLAKSLAILLGVFAVCWAPYSLFTIVLSFYSSATGPKSVWYRIAFWLQWFN    281 - 350
SFVNPLLYPLCHKRFQKAFLKIFCIKKQPLPSQHSRSVSS                                  351 - 390
//

Text Mined References (81)

PMID Year Title
26828993 2016 Histamine H4 Receptor mediates interleukin-8 and TNF-? release in human mast cells via multiple signaling pathways.
26823878 2015 Association between HRH4 polymorphisms and ankylosing spondylitis susceptibility.
25300787 2015 A search for functional histamine H4 receptors in the human, guinea pig and mouse brain.
25293806 2014 Gene expression analysis of histamine receptors in peripheral blood mononuclear cells from individuals with clinically-isolated syndrome and different stages of multiple sclerosis.
25273276 2014 No evidence for histamine H4 receptor in human monocytes.
25098339 2014 Sodium binding to hH3R and hH 4R--a molecular modeling study.
24934979 2014 Functional characterization of histamine H4 receptor on human mast cells.
24799603 2014 The histamine H4 receptor is a potent inhibitor of adhesion-dependent degranulation in human neutrophils.
24787705 2014 Histamine H4 receptor as a new therapeutic target for choroidal neovascularization in age-related macular degeneration.
24530738 2014 Role of histamine receptors in the effects of histamine on the production of reactive oxygen species by whole blood phagocytes.
24493592 2014 Synthesis and functional characterization of imbutamine analogs as histamine H3 and H4 receptor ligands.
24447834 2014 Activation of histamine H4 receptors decreases epithelial-to-mesenchymal transition progress by inhibiting transforming growth factor-?1 signalling pathway in non-small cell lung cancer.
24432340 2013 Development of novel cellular model for affinity studies of histamine H(4) receptor ligands.
24372819 2014 Increased expression of the histamine H4 receptor following differentiation and mediation of the H4 receptor on interleukin-8 mRNA expression in HaCaT keratinocytes.
24236486 2013 Variability in histamine receptor genes HRH1, HRH2 and HRH4 in patients with hypersensitivity to NSAIDs.
23932072 2013 Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor.
23677734 2013 The neglected role of histamine in Alzheimer's disease.
23517361 2013 Association between copy-number variations of the human histamine H4 receptor gene and atopic dermatitis in a Chinese population.
23481304 2013 Polymorphisms of human histamine receptor H4 gene are associated with breast cancer in Chinese Han population.
23425150 2013 Therapeutic potential of histamine H? receptor agonists in triple-negative human breast cancer experimental model.
23006423 2012 Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study.
22973061 2012 Analysis of multiple histamine H? receptor compound classes uncovers G?i protein- and ?-arrestin2-biased ligands.
22885137 2012 Voltage sensitivities and deactivation kinetics of histamine H? and H? receptors.
22653292 2012 Asthma endophenotypes and polymorphisms in the histamine receptor HRH4 gene.
22363581 2012 Deletion and down-regulation of HRH4 gene in gastric carcinomas: a potential correlation with tumor progression.
22201741 2012 Computerized modeling techniques predict the 3D structure of H?R: facts and fiction.
22153663 2012 Ligand based design of novel histamine H? receptor antagonists; fragment optimization and analysis of binding kinetics.
22118942 2012 Alterations in the histaminergic system in the substantia nigra and striatum of Parkinson's patients: a postmortem study.
21881994 2012 Lower expression of histamine H? receptor in synovial tissues from patients with rheumatoid arthritis compared to those with osteoarthritis.
21741967 2011 The histamine H? receptor: targeting inflammatory disorders.
21614010 2011 The histamine H4 receptor is highly expressed on plasmacytoid dendritic cells in psoriasis and histamine regulates their cytokine production and migration.
21609450 2011 Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression.
21171298 2010 [Different expression of histamine H4 receptor in nasal mucosa in allergic rhinitis patients].
21104170 2011 The role of the histamine H4 receptor in atopic dermatitis.
20800603 2010 Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
20722760 2011 Histamine H(4) receptor activation on human slan-dendritic cells down-regulates their pro-inflammatory capacity.
20618322 2010 Copy number variations of the human histamine H4 receptor gene are associated with systemic lupus erythematosus.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20199554 2010 Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis.
20192225 2010 Synthesis and QSAR of quinazoline sulfonamides as highly potent human histamine H4 receptor inverse agonists.
19958313 2010 Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and function.
19662098 2009 H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.
19281909 2009 The histamine H4 receptor is functionally expressed on T(H)2 cells.
19271148 2009 Morphology and immuno-distribution of the histamine H4 receptor and histamine--releasing factor in choroid plexus of patients with paraneoplastic cerebellar degeneration.
19166345 2009 High constitutive activity and a G-protein-independent high-affinity state of the human histamine H(4)-receptor.
19156168 2009 Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.
19053770 2008 Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach.
19046950 2009 Localization of histamine H4 receptors in the central nervous system of human and rat.
18635748 2008 Phenylalanine 169 in the second extracellular loop of the human histamine H4 receptor is responsible for the difference in agonist binding between human and mouse H4 receptors.
18582456 2008 Electrophysiology-based analysis of human histamine H(4) receptor pharmacology using GIRK channel coupling in Xenopus oocytes.
18577758 2008 Dissociation of heterotrimeric g proteins in cells.
18572901 2008 Activation mechanism of the human histamine H4 receptor--an explicit membrane molecular dynamics simulation study.
18452403 2008 Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor.
18345506 2008 Histamine regulates pancreatic carcinoma cell growth through H3 and H4 receptors.
18345495 2008 Histamine receptor H4R-selective ligands influence the STAT6 Transcription Activation Domain (TAD) and the DNA-binding.
18345487 2008 Expression of histamine H4 receptor in human osteoarthritic synovial tissue.
18258331 2008 Decreased expression of histamine H1 and H4 receptors suggests disturbance of local regulation in human colorectal tumours by histamine.
18240029 2008 Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors.
18239617 2008 Human inflammatory dendritic epidermal cells express a functional histamine H4 receptor.
17978505 2007 Expression of histamine H4 receptor in synovial cells from rheumatoid arthritic patients.
17806182 2007 Distribution pattern of histamine H4 receptor in human synovial tissue from patients with rheumatoid arthritis.
17806168 2007 Histamine H4 receptors in human placenta in diabetes-complicated pregnancy.
17681365 2007 H4 histamine receptor mediates optimal migration of mast cell precursors to CXCL12.
17627982 2007 Histamine excites neurones in the human submucous plexus through activation of H1, H2, H3 and H4 receptors.
17507084 2007 Histamine downregulates monocyte CCL2 production through the histamine H4 receptor.
16547812 2006 The role of the histamine H(4) receptor in signal transduction of atopic and non-atopic human lymphocytes ex vivo.
16547802 2006 Histamine H(4) receptors on mammary epithelial cells of the human breast with different types of carcinoma.
16203768 2005 The role of cyclooxygenase-2 in mediating the effects of histamine on cell proliferation and vascular endothelial growth factor production in colorectal cancer.
16177791 2005 DNA sequence and analysis of human chromosome 18.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15265943 2004 Liver-expressed chemokine/CC chemokine ligand 16 attracts eosinophils by interacting with histamine H4 receptor.
15191551 2004 Human skin mast cells express H2 and H4, but not H3 receptors.
12503632 Identification of a histamine H4 receptor on human eosinophils--role in eosinophil chemotaxis.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11394877 2001 Structure and expression of the human histamine H4-receptor gene.
11181941 2001 Cloning and characterization of a novel human histamine receptor.
11179436 2001 Cloning, expression, and pharmacological characterization of a novel human histamine receptor.
11179435 2001 Discovery of a novel member of the histamine receptor family.
11179434 2001 Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow.
11118334 2000 Molecular cloning and characterization of a new human histamine receptor, HH4R.
10973974 2000 Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes.