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Aliases for HRH4 Gene

Aliases for HRH4 Gene

  • Histamine Receptor H4 2 3
  • HH4R 3 4 6
  • G-Protein Coupled Receptor 105 3 4
  • Pfi-013 3 4
  • GPCR105 3 4
  • AXOR35 3 4
  • GPRv53 3 4
  • SP9144 3 4
  • H4R 3 4
  • Histamine H4 Receptor 3
  • 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 cerebellar degeneration and paraneoplastic cerebellar degeneration. Among its related pathways are Signaling by GPCR and Akt Signaling. GO annotations related to this gene include histamine receptor activity. 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 haematopoietic cells, including eosinophils, basophils, mast cells, T lymphocytes, leukocytes and dendritic cells. Moderate expression levels are detected in the brain, heart, liver and lung. H4 receptors have an important role in inflammation, haematopoiesis and immunity and their expression is regulated by stimuli such as IFN, TNF-alpha and IL-6. Activation of this receptor mediates chemotaxis of mast cells and eosinophils and also controls cytokine release from dendritic and T cells. Furthermore, H4 receptors have a role in the differentiation of myeloblasts and promyelocytes. The human gene encoding the H4 receptor is localized to chromosome 18q11.2.

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

Genomic Location for HRH4 Gene

24,460,629 bp from pter
24,479,957 bp from pter
19,329 bases
Plus strand

Genomic View for HRH4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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:
    Recommended name:
    Histamine H4 receptor
    Protein Accession:
    Secondary Accessions:
    • B0YJ19
    • B2KJ48
    • Q4G0I6
    • Q9GZQ0

    Protein attributes for HRH4 Gene

    390 amino acids
    Molecular mass:
    44496 Da
    Quaternary structure:
    No Data Available
    • 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


neXtProt entry for HRH4 Gene

Proteomics data for HRH4 Gene at MOPED

Post-translational modifications for HRH4 Gene

  • Glycosylation at Asn5 and Asn9
  • Modification sites at PhosphoSitePlus

Other Protein References for HRH4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for HRH4 Gene

Domains 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



  • Belongs to the G-protein coupled receptor 1 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

Gene Ontology (GO) - Molecular Function for HRH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G-protein coupled receptor activity --
GO:0004969 histamine receptor activity NAS 10973974
GO:0051381 histamine binding IBA --
genes like me logo Genes that share ontologies with HRH4: view
genes like me logo Genes that share phenotypes with HRH4: view

Animal Models for HRH4 Gene

MGI Knock Outs for HRH4:

Animal Model Products

miRNA for HRH4 Gene

miRTarBase miRNAs that target HRH4

No data available for Enzyme Numbers (IUBMB) , 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

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

Gene Ontology (GO) - Cellular Components for HRH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IBA --
GO:0016020 membrane --
GO:0016021 integral component of membrane --
genes like me logo Genes that share ontologies with HRH4: view

Pathways for HRH4 Gene

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

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

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 --
GO:0007194 negative regulation of adenylate cyclase activity IBA --
GO:0007204 positive regulation of cytosolic calcium ion concentration IEA --
GO:0007606 sensory perception of chemical stimulus IBA --
genes like me logo Genes that share ontologies with HRH4: view

Drugs for HRH4 Gene

(10) Drugbank Compounds for HRH4 Gene

Compound Status Synonyms Cas Number PubChem ID Type Actions PubMed IDs
  • 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine
132539-06-1 Target antagonist approved, investigational
  • 10,11-dihydro-5-(gamma-Dimethylaminopropylidene)-5H-dibenzo(a,D)cycloheptene
50-48-6 2160 Target binder approved
  • 2-Chloro-11-(1-piperazinyl)dibenz(b,F)(1,4)oxazepine
14028-44-5 2170 Target binder approved
  • 3-(2-chloro-10H-Phenothiazin-10-yl)-N,N-dimethyl-1-propanamine
50-53-3 2726 Target binder approved
  • Clozapin
5786-21-0 2818 Target antagonist approved

(5) Tocris Compounds for HRH4 Gene

Compound Action Cas Number
4-Methylhistamine dihydrochloride Selective, high affinity H4 agonist [36376-47-3]
A 943931 dihydrochloride Potent and selective H4 antagonist [1227675-50-4]
Histamine dihydrochloride Endogenous histamine receptor agonist [56-92-8]
JNJ 10191584 maleate Selective H4 receptor antagonist; orally active [869497-75-6]
VUF 10460 Selective H4 agonist [1028327-66-3]

(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]

(4) HMDB Compounds for HRH4 Gene

Compound Synonyms Cas Number PubMed IDs
  • Chlor-trimeton
Cyclic AMP
  • 3'5'-Cyclic AMP
  • 1H-Imidazole-4-ethanamine
Histamine Phosphate

(33) IUPHAR Ligand for HRH4 Gene

Ligand Type Action Affinity Pubmed IDs
immepip Agonist Full agonist 9.7
imetit Agonist Full agonist 9.7
N-methylhistamine Agonist Full agonist 9.3
(R)-alpha-methylhistamine Agonist Full agonist 9.2
[3H](R)-alpha-methylhistamine Agonist Full agonist 9.2
N-[3H]methylhistamine Agonist Full agonist 9.1
methimepip Agonist Full agonist 9
iodophenpropit Antagonist Antagonist 8.7
[3H]JNJ 7777120 Antagonist Antagonist 8.4
histamine Agonist Full agonist 8.3
JNJ 7777120 Antagonist Antagonist 8.3
4-methylhistamine Agonist Full agonist 8.2
CCL16 Agonist Full agonist 8.1
[3H]histamine Agonist Full agonist 8
[125I]CCL16 (human) Agonist Full agonist 7.8
thioperamide Antagonist Antagonist 7.7
JNJ-10191584 Antagonist Antagonist 7.7
(S)-alpha-methylhistamine Agonist Full agonist 7.6
VUF 8430 Agonist Full agonist 7.5
[3H]pyrilamine Antagonist Antagonist 7.5
ciproxifan Antagonist Antagonist 7.3
impromidine Agonist Full agonist 7.2
N-alpha-methylhistamine Agonist Full agonist 7.2
N-ethylhistamine Agonist Full agonist 6.7
clozapine Antagonist Antagonist 6.7
2-methylhistamine Agonist Full agonist 6.6
dimaprit Agonist Full agonist 6.1
2-(3-bromophenyl)histamine Agonist Full agonist 6
N,N-dimethylhistamine Agonist Full agonist 5.9
HTMT Agonist Full agonist 5.9
burimamide Agonist Full agonist 5.7
clobenpropit Antagonist Antagonist 5.2
improgan Agonist Full agonist 5.2

(7) Novoseek inferred chemical compound relationships for HRH4 Gene

Compound -log(P) Hits PubMed IDs
4-methylhistamine 93 5
clobenpropit 92.5 6
thioperamide 87.3 3
histamine 84.1 40
clozapine 48.6 1

(1) PharmGKB related drug/compound annotations for HRH4 Gene

Drug/compound Annotation
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:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for HRH4

Flow Cytometry Products

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

No ASD Table

Relevant External Links for HRH4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

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 (12.1).

Integrated Proteomics: protein expression 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

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 expressions 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 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
(Bos Taurus)
Mammalia HRH4 35
  • 78.15 (n)
  • 68.67 (a)
HRH4 36
  • 68 (a)
(Canis familiaris)
Mammalia HRH4 35
  • 82.09 (n)
  • 72.75 (a)
HRH4 36
  • 69 (a)
(Mus musculus)
Mammalia Hrh4 35
  • 75.66 (n)
  • 68.89 (a)
Hrh4 16
Hrh4 36
  • 68 (a)
(Pan troglodytes)
Mammalia HRH4 35
  • 99.23 (n)
  • 98.72 (a)
HRH4 36
  • 99 (a)
(Rattus norvegicus)
Mammalia Hrh4 35
  • 74.81 (n)
  • 69.92 (a)
(Monodelphis domestica)
Mammalia HRH4 36
  • 52 (a)
(Ornithorhynchus anatinus)
Mammalia HRH4 36
  • 41 (a)
(Gallus gallus)
Aves -- 36
  • 35 (a)
-- 36
  • 52 (a)
(Anolis carolinensis)
Reptilia -- 36
  • 34 (a)
(Danio rerio)
Actinopterygii CABZ01078515.1 36
  • 37 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG7918 36
  • 10 (a)
(Caenorhabditis elegans)
Secernentea gar-1 36
  • 13 (a)
gar-2 36
  • 13 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 17 (a)
-- 36
  • 17 (a)
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

Gene Tree for HRH4 (if available)
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 MAF
rs104000 -- 24,471,115(+) CCTTA(A/G)CATCG intron-variant
rs472407 -- 24,479,493(-) CCTGC(A/G)TGGGC utr-variant-3-prime
rs475997 -- 24,479,130(-) TTcca(A/G)cctga utr-variant-3-prime
rs476042 -- 24,479,114(-) atggc(A/G)aaacc utr-variant-3-prime
rs476076 -- 24,479,090(-) aaata(C/T)caaaa utr-variant-3-prime

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

Relevant External Links for HRH4 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

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

Disorders for HRH4 Gene

MalaCards: The human disease database

MalaCards: The human disease database.

Search for HRH4 Gene in MalaCards »

(2) Diseases for HRH4 Gene

(3) University of Copenhagen DISEASES for HRH4 Gene

(5) Novoseek inferred disease relationships for HRH4 Gene

Disease -log(P) Hits PubMed IDs
allergic reaction 39.7 2
dermatitis atopic 37.7 2
allergy 33.9 2
inflammation 29.4 4
asthma 26.8 3

Relevant External Links for HRH4

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with HRH4: view

No data available for OMIM , 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
  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 48
  3. Cloning and pharmacological characterization of a fourth histamine receptor (H4) expressed in bone marrow. (PMID: 11179434) Liu C. … Lovenberg T.W. (Mol. Pharmacol. 2001) 3 4 23
  4. Cloning, expression, and pharmacological characterization of a novel human histamine receptor. (PMID: 11179436) Zhu Y. … Fitzgerald L.R. (Mol. Pharmacol. 2001) 3 4 23
  5. Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. (PMID: 10973974) Oda T. … Matsumoto S. (J. Biol. Chem. 2000) 2 3 4

Products for HRH4 Gene

Sources for HRH4 Gene

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