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Aliases for HRH4 Gene

Aliases for HRH4 Gene

  • Histamine Receptor H4 2 3 5
  • G-Protein Coupled Receptor 105 3 4
  • Pfi-013 3 4
  • GPCR105 3 4
  • AXOR35 3 4
  • GPRv53 3 4
  • SP9144 3 4
  • HH4R 3 4
  • H4R 3 4
  • BG26 3
  • H4 3

External Ids for HRH4 Gene

Previous GeneCards Identifiers for HRH4 Gene

  • GC18P021933
  • GC18P021772
  • GC18P020292
  • GC18P020294
  • GC18P022040
  • GC18P018896

Summaries for HRH4 Gene

Entrez Gene Summary for HRH4 Gene

  • Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by a family of histamine receptors, which are a subset of the G-protein coupled receptor superfamily. This gene encodes a histamine receptor that is predominantly expressed in haematopoietic cells. The protein is thought to play a role in inflammation and allergy reponses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

GeneCards Summary for HRH4 Gene

HRH4 (Histamine Receptor H4) is a Protein Coding gene. Diseases associated with HRH4 include paraneoplastic cerebellar degeneration and allergic hypersensitivity disease. Among its related pathways are Signaling by GPCR and ERK Signaling. GO annotations related to this gene include G-protein coupled receptor activity and histamine binding. An important paralog of this gene is CHRM4.

UniProtKB/Swiss-Prot for HRH4 Gene

  • The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).

Tocris Summary for HRH4 Gene

  • Histamine H4 receptors are Galphai/o-protein-coupled receptors, first cloned in 2000. H4 receptors are expressed at high levels in the gastrointestinal tract, spleen, thymus, medullary cells, bone marrow and peripheral hematopoietic cells, including eosinophils and T lymphocytes.

Gene Wiki entry for HRH4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HRH4 Gene

Genomics for HRH4 Gene

Regulatory Elements for HRH4 Gene

Promoters for HRH4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around HRH4 on UCSC Golden Path with GeneCards custom track

Genomic Location for HRH4 Gene

Chromosome:
18
Start:
24,460,568 bp from pter
End:
24,487,427 bp from pter
Size:
26,860 bases
Orientation:
Plus strand

Genomic View for HRH4 Gene

Genes around HRH4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HRH4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HRH4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HRH4 Gene

Proteins for HRH4 Gene

  • Protein details for HRH4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H3N8-HRH4_HUMAN
    Recommended name:
    Histamine H4 receptor
    Protein Accession:
    Q9H3N8
    Secondary Accessions:
    • B0YJ19
    • B2KJ48
    • Q4G0I6
    • Q9GZQ0

    Protein attributes for HRH4 Gene

    Size:
    390 amino acids
    Molecular mass:
    44496 Da
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • Does not bind diphenhydramine, loratadine, ranitidine, cimetidine and chlorpheniramine. Shows modest affinity for dimaprit, impromidine, clobenpropit, thioperamide, burimamide clozapine, immepip and imetit. The order of inhibitory activity was imetit > clobenpropit > burimamide > thioperamide. Clobenpropit behaves as a partial agonist, dimaprit and impromidine show some agonist activity while clozapine behaves as a full agonist. Thioperamide shows inverse agonism (enhances cAMP activity). The order of inhibitory activity of histamine derivatives was Histamine > N-alpha-methylhistamine > R(-)-alpha-methylhistamine > S(+)-alpha-methylhistamine. Both N-alpha-methylhistamine > R(-)-alpha-methylhistamine behave as full agonists.

    Alternative splice isoforms for HRH4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HRH4 Gene

Proteomics data for HRH4 Gene at MOPED

Post-translational modifications for HRH4 Gene

  • Glycosylation at Asn 5 and Asn 9
  • Modification sites at PhosphoSitePlus

Other Protein References for HRH4 Gene

Antibody Products

No data available for DME Specific Peptides for HRH4 Gene

Domains & Families for HRH4 Gene

Gene Families for HRH4 Gene

Protein Domains for HRH4 Gene

Suggested Antigen Peptide Sequences for HRH4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9H3N8

UniProtKB/Swiss-Prot:

HRH4_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with HRH4: view

Function for HRH4 Gene

Molecular function for HRH4 Gene

UniProtKB/Swiss-Prot Function:
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
UniProtKB/Swiss-Prot Induction:
Expression is either up-regulated or down-regulated upon activation of the lymphoid tissues and this regulation may depend on the presence of IL10/interleukin-10 or IL13/interleukin-13.
genes like me logo Genes that share phenotypes with HRH4: view

Animal Models for HRH4 Gene

MGI Knock Outs for HRH4:

Animal Model Products

  • Taconic Biosciences Mouse Models for HRH4

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HRH4 Gene

Localization for HRH4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HRH4 Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HRH4 Gene COMPARTMENTS Subcellular localization image for HRH4 gene
Compartment Confidence
plasma membrane 5
cytosol 2
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for HRH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with HRH4: view

Pathways & Interactions for HRH4 Gene

genes like me logo Genes that share pathways with HRH4: view

Pathways by source for HRH4 Gene

Gene Ontology (GO) - Biological Process for HRH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006954 inflammatory response IBA --
GO:0007186 G-protein coupled receptor signaling pathway IEA --
GO:0007197 adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway IBA --
GO:0007271 synaptic transmission, cholinergic IBA --
genes like me logo Genes that share ontologies with HRH4: view

No data available for SIGNOR curated interactions for HRH4 Gene

Drugs & Compounds for HRH4 Gene

(81) Drugs for HRH4 Gene - From: IUPHAR, DGIdb, Novoseek, ApexBio, HMDB, DrugBank, and PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Clozapine Approved Pharma Antagonist, antagonist, Target Antipsychotic medication, Dopamine antagonist with some D4 selectivity. Also 5-HT2A/2C antagonist 113
Histamine Phosphate Approved Pharma Target, agonist 906
Chlorpheniramine Approved Pharma 59
Amitriptyline Approved Pharma Antagonist, Target, binder 100
Amoxapine Approved Pharma Antagonist, Target, binder GLYT2a transport activity inhibitor 0

(10) Additional Compounds for HRH4 Gene - From: IUPHAR, Tocris, and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
(<i>R</i>)-alpha-methylhistamine
Full agonist, Agonist
(<i>S</i>)-alpha-methylhistamine
Full agonist, Agonist
[<sup>3</sup>H](<i>R</i>)-alpha-methylhistamine
Full agonist, Agonist
<i>N</i>-alpha-methylhistamine
Full agonist, Agonist
4-Methylhistamine dihydrochloride
36376-47-3

(5) Tocris Compounds for HRH4 Gene

Compound Action Cas Number
4-Methylhistamine dihydrochloride Selective, high affinity H4 agonist 36376-47-3
Clobenpropit dihydrobromide Highly potent H3 antagonist and H4 partial agonist 145231-35-2
Imetit dihydrobromide Standard H3 and H4 agonist (H3 > H4) 32385-58-3
Immepip dihydrobromide Standard H3 agonist. Also H4 agonist 164391-47-3
VUF 8430 dihydrobromide Potent, high affinity H4 agonist 100130-32-3

(38) ApexBio Compounds for HRH4 Gene

Compound Action Cas Number
Astemizole 68844-77-9
Azatadine dimaleate 3978-86-7
Azelastine HCl 79307-93-0
Benztropine mesylate 132-17-2
Bepotastine Besilate 190786-44-8
Betahistine 2HCl 5579-84-0
Brompheniramine hydrogen maleate 980-71-2
Buclizine HCl 129-74-8
Cetirizine DiHCl H1 receptor inverse agonist 83881-52-1
Chlorpheniramine Maleate 113-92-8
Cimetidine H2 receptor antagonist 51481-61-9
Ciproxifan Histamine H3-receptor antagonist 184025-18-1
Clemastine Fumarate 14976-57-9
Cyclizine 2HCl 5897-18-7
Cyproheptadine hydrochloride 969-33-5
Desloratadine 100643-71-8
Epinastine HCl 108929-04-0
Famotidine Histamine H2-receptor antagonist 76824-35-6
Fexofenadine HCl 153439-40-8
Histamine 2HCl 56-92-8
Histamine Phosphate 51-74-1
Hydroxyzine 2HCl 2192-20-3
JNJ-7777120 Histamine H4 receptor antagonist 459168-41-3
Ketotifen Fumarate 34580-14-8
Lafutidine 118288-08-7
Levodropropizine Histamine receptor inhibitor,cough suppressant 99291-25-5
Lidocaine Anasthetic and class Ib antiarrhythmic agent 137-58-6
Loratadine Peripheral HH1R antagonist 79794-75-5
Mianserin HCl 5-HT2 receptor antagonist 21535-47-7
Mizolastine 108612-45-9
Nizatidine 76963-41-2
Olopatadine HCl Histamine blocker 140462-76-6
Pemirolast potassium 100299-08-9
Ranitidine Histamine H2-receptor antagonist 66357-59-3
Roxatidine Acetate HCl 93793-83-0
Rupatadine Fumarate 182349-12-8
Serotonin HCl 153-98-0
Tripelennamine HCl H1-receptor antagonist 154-69-8
genes like me logo Genes that share compounds with HRH4: view

Transcripts for HRH4 Gene

mRNA/cDNA for HRH4 Gene

(5) REFSEQ mRNAs :
(13) Additional mRNA sequences :
(13) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for HRH4 Gene

Histamine receptor H4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HRH4 Gene

No ASD Table

Relevant External Links for HRH4 Gene

GeneLoc Exon Structure for
HRH4
ECgene alternative splicing isoforms for
HRH4

Expression for HRH4 Gene

mRNA expression in normal human tissues for HRH4 Gene

mRNA differential expression in normal tissues according to GTEx for HRH4 Gene

This gene is overexpressed in Whole Blood (x12.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for HRH4 Gene



SOURCE GeneReport for Unigene cluster for HRH4 Gene Hs.287388

mRNA Expression by UniProt/SwissProt for HRH4 Gene

Q9H3N8-HRH4_HUMAN
Tissue specificity: Expressed primarily in the bone marrow and eosinophils. Shows preferential distribution in cells of immunological relevance such as T-cells, dendritic cells, monocytes, mast cells, neutrophils. Also expressed in a wide variety of peripheral tissues, including the heart, kidney, liver, lung, pancreas, skeletal muscle, prostate, small intestine, spleen, testis, colon, fetal liver and lymph node.
genes like me logo Genes that share expression patterns with HRH4: view

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues and Protein tissue co-expression partners for HRH4 Gene

Orthologs for HRH4 Gene

This gene was present in the common ancestor of animals.

Orthologs for HRH4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia HRH4 35
  • 78.15 (n)
  • 68.67 (a)
HRH4 36
  • 68 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HRH4 35
  • 82.09 (n)
  • 72.75 (a)
HRH4 36
  • 69 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Hrh4 35
  • 75.66 (n)
  • 68.89 (a)
Hrh4 16
Hrh4 36
  • 68 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia HRH4 35
  • 99.23 (n)
  • 98.72 (a)
HRH4 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hrh4 35
  • 74.81 (n)
  • 69.92 (a)
oppossum
(Monodelphis domestica)
Mammalia HRH4 36
  • 52 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HRH4 36
  • 41 (a)
OneToOne
chicken
(Gallus gallus)
Aves -- 36
  • 35 (a)
OneToMany
-- 36
  • 52 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 34 (a)
ManyToMany
zebrafish
(Danio rerio)
Actinopterygii CABZ01078515.1 36
  • 37 (a)
ManyToMany
fruit fly
(Drosophila melanogaster)
Insecta CG7918 36
  • 10 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea gar-1 36
  • 13 (a)
ManyToMany
gar-2 36
  • 13 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 17 (a)
ManyToMany
-- 36
  • 17 (a)
ManyToMany
Species with no ortholog for HRH4:
  • A. gosspyii yeast (Ashbya 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)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for HRH4 Gene

ENSEMBL:
Gene Tree for HRH4 (if available)
TreeFam:
Gene Tree for HRH4 (if available)

Paralogs for HRH4 Gene

Paralogs for HRH4 Gene

(2) SIMAP similar genes for HRH4 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with HRH4: view

Variants for HRH4 Gene

Sequence variations from dbSNP and Humsavar for HRH4 Gene

SNP ID Clin Chr 18 pos Sequence Context AA Info Type
rs11665084 - 24,476,802(+) GGTGG(C/T)CGTTT intron-variant, reference, missense, utr-variant-3-prime
rs11662595 - 24,477,006(+) TGATC(A/G)TCTCA intron-variant, reference, missense, utr-variant-3-prime
rs484069 -- 24,486,209(-) CCAAA(G/T)GGGCG intron-variant
rs104000 -- 24,471,115(+) CCTTA(A/G)CATCG intron-variant
rs487202 -- 24,482,852(-) TAGCT(C/G)TTTTC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for HRH4 Gene

Variant ID Type Subtype PubMed ID
nsv909461 CNV Gain 21882294
nsv521369 CNV Gain 19592680
esv2716869 CNV Deletion 23290073

Variation tolerance for HRH4 Gene

Residual Variation Intolerance Score: 52.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.51; 71.90% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HRH4 Gene

HapMap Linkage Disequilibrium report
HRH4
Human Gene Mutation Database (HGMD)
HRH4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HRH4 Gene

Disorders for HRH4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for HRH4 Gene - From: DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search HRH4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for HRH4

Genetic Association Database (GAD)
HRH4
Human Genome Epidemiology (HuGE) Navigator
HRH4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HRH4
genes like me logo Genes that share disorders with HRH4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HRH4 Gene

Publications for HRH4 Gene

  1. Molecular cloning and characterization of a new human histamine receptor, HH4R. (PMID: 11118334) Nakamura T. … Tanaka K. (Biochem. Biophys. Res. Commun. 2000) 2 3 4 23 67
  2. Copy number variations of the human histamine H4 receptor gene are associated with systemic lupus erythematosus. (PMID: 20618322) Yu B. … Zhang W. (Br. J. Dermatol. 2010) 3 25 26
  3. Synthesis and QSAR of quinazoline sulfonamides as highly potent human histamine H4 receptor inverse agonists. (PMID: 20192225) Smits R.A. … de Esch I.J. (J. Med. Chem. 2010) 3 23
  4. Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis. (PMID: 20199554) Yu B. … Wan J. (Br. J. Dermatol. 2010) 3 23
  5. Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines. (PMID: 20573261) Cowden J.M. … Dunford P.J. (Respir. Res. 2010) 25 26

Products for HRH4 Gene

Sources for HRH4 Gene

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