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Aliases for HRH4 Gene

Aliases for HRH4 Gene

  • Histamine Receptor H4 2 3
  • 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 pericarditis. Among its related pathways are Signaling by GPCR and Akt 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

Genomic Location for HRH4 Gene

24,460,568 bp from pter
24,487,427 bp from pter
26,860 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 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



  • 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

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
cytosol 2

Gene Ontology (GO) - Cellular Components for HRH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol IEA --
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 & Interactions 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

No data available for SIGNOR curated interactions for HRH4 Gene

Drugs & Compounds for HRH4 Gene

(82) Drugs for HRH4 Gene - From: NovoSeek, IUPHAR, DGIdb, ApexBio, HMDB, DrugBank, PharmGKB, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Clozapine Approved Pharma Antagonist, antagonist, Target Antipsychotic medication 108
Histamine Phosphate Approved Pharma Target, agonist 852
Chlorpheniramine Approved Pharma 54
Amitriptyline Approved Pharma Antagonist, Target, binder 96
Amoxapine Approved Pharma Antagonist, Target, binder GLYT2a transport activity inhibitor 0

(9) Additional Compounds for HRH4 Gene - From: IUPHAR, Tocris, and NovoSeek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Full agonist, Agonist
Full agonist, Agonist
Full agonist, Agonist
Full agonist, Agonist
4-Methylhistamine dihydrochloride
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 (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

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
(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, intron-variant
rs472600 -- 24,487,284(-) AGCTT(C/T)AGCAC utr-variant-3-prime
rs475997 -- 24,479,130(-) TTcca(A/G)cctga utr-variant-3-prime, intron-variant
rs476042 -- 24,479,114(-) atggc(A/G)aaacc utr-variant-3-prime, 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: 52.36% 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
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

(2) MalaCards diseases for HRH4 Gene - From: DISEASES and GeneCards

- elite association
Search HRH4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for HRH4

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
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. 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) 25 26 67
  2. Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T-cell responses. (PMID: 17346280) Sugata Y. … Nishizaki K. (Immunology 2007) 23 25 67
  3. Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. (PMID: 16854056) Smits R.A. … Leurs R. (J. Med. Chem. 2006) 23 25 67
  4. Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. (PMID: 15947036) Lim H.D. … Leurs R. (J. Pharmacol. Exp. Ther. 2005) 23 25 67
  5. Molecular cloning and characterization of a new human histamine receptor, HH4R. (PMID: 11118334) Nakamura T. … Tanaka K. (Biochem. Biophys. Res. Commun. 2000) 2 23 67

Products for HRH4 Gene

Sources for HRH4 Gene

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