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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
  • 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 Paraneoplastic Cerebellar Degeneration and Allergic Hypersensitivity Disease. Among its related pathways are Peptide ligand-binding receptors and CCR5 Pathway in Macrophages. GO annotations related to this gene include G-protein coupled receptor activity and histamine binding. An important paralog of this gene is HRH3.

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 CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HRH4 Gene

Genomics for HRH4 Gene

Regulatory Elements for HRH4 Gene

Enhancers for HRH4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH18G024514 0.6 ENCODE 10.7 +54.1 54054 0.1 CTCF E2F5 CEBPB USF2 CEBPG JUND NFYB ZNF341 FOS MAFK HRH4 ENSG00000266489 LOC646629
GH18G024465 0.4 Ensembl 0.7 +4.9 4933 0.2 HNF4A HRH4 ENSG00000264695
GH18G024487 0.7 ENCODE 0.3 +27.3 27304 0.2 CTCF ZNF654 TRIM22 REST ZNF2 RAD21 FOXA1 ZSCAN21 SCRT2 SMC3 ENSG00000264695 HRH4
GH18G024488 0.7 Ensembl 0.3 +27.5 27533 0.2 CTCF PKNOX1 ZSCAN4 TRIM22 REST ZNF2 RAD21 ZSCAN21 ZFHX2 SCRT2 ENSG00000264695 HRH4
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around HRH4 on UCSC Golden Path with GeneCards custom track

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

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:
    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

Post-translational modifications for HRH4 Gene

  • Glycosylation at posLast=55 and posLast=99
  • Modification sites at PhosphoSitePlus

Other Protein References for HRH4 Gene

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 IEA --
GO:0004969 histamine receptor activity NAS 10973974
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

  • Taconic Biosciences Mouse Models for HRH4

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for HRH4
  • Applied Biological Materials Clones for HRH4

No data available for Enzyme Numbers (IUBMB) , 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

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
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:0016020 membrane 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

Gene Ontology (GO) - Biological Process for HRH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006954 inflammatory response IBA --
GO:0007165 signal transduction IEA --
GO:0007186 G-protein coupled receptor signaling pathway IEA --
GO:0007204 positive regulation of cytosolic calcium ion concentration IEA --
GO:0008150 biological_process ND --
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

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Histamine Approved, Investigational Pharma Full agonist, Agonist, Target, agonist 1050
Clozapine Approved Pharma Antagonist, antagonist, Target Antipsychotic medication 117
Amitriptyline Approved Pharma Antagonist, Target, binder 110
Amoxapine Approved Pharma Antagonist, Target, binder GLYT2a transport activity inhibitor 0
Chlorpromazine Approved, Vet_approved Pharma Antagonist, Target, binder 18

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Full agonist, Agonist
Full agonist, Agonist
Full agonist, Agonist
Full agonist, Agonist
Histamine dihydrochloride

(5) Tocris Compounds for HRH4 Gene

Compound Action Cas Number
4-Methylhistamine dihydrochloride Selective, high affinity H4 agonist 36376-47-3
Histamine dihydrochloride Endogenous histamine receptor agonist 56-92-8
JNJ 10191584 maleate Selective H4 receptor antagonist; orally active 869497-75-6
JNJ 7777120 Selective H4 receptor antagonist 459168-41-3
VUF 8430 dihydrobromide Potent, high affinity H4 agonist 100130-32-3

(42) ApexBio Compounds for HRH4 Gene

Compound Action Cas Number
4-Methylhistamine dihydrochloride H4 receptor agonist,potent and high affinity 36376-47-3
A 943931 dihydrochloride Antagonist of histamine H4 receptor,potent and selective 1227675-50-4
A 987306 H4 receptor antagonist,potent and selective 1082954-71-9
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 Antihistamine 83881-51-0
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

Drug Products

Transcripts for HRH4 Gene

mRNA/cDNA for HRH4 Gene

(4) 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

Clone Products

  • Addgene plasmids for HRH4
  • Applied Biological Materials Clones for HRH4

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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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

NURSA nuclear receptor signaling pathways regulating expression of HRH4 Gene:


SOURCE GeneReport for Unigene cluster for HRH4 Gene:


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.

Evidence on tissue expression from TISSUES for HRH4 Gene

  • Blood(4.4)
  • Bone marrow(4.3)
genes like me logo Genes that share expression patterns with HRH4: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer 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
(Pan troglodytes)
Mammalia HRH4 34 35
  • 99.23 (n)
(Canis familiaris)
Mammalia HRH4 34 35
  • 82.09 (n)
(Bos Taurus)
Mammalia HRH4 35 34
  • 78.15 (n)
(Mus musculus)
Mammalia Hrh4 34 16 35
  • 75.66 (n)
(Rattus norvegicus)
Mammalia Hrh4 34
  • 74.81 (n)
(Monodelphis domestica)
Mammalia HRH4 35
  • 52 (a)
(Ornithorhynchus anatinus)
Mammalia HRH4 35
  • 41 (a)
(Gallus gallus)
Aves -- 35
  • 52 (a)
-- 35
  • 35 (a)
(Anolis carolinensis)
Reptilia -- 35
  • 34 (a)
(Danio rerio)
Actinopterygii CABZ01078515.1 35
  • 37 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG7918 35
  • 10 (a)
(Caenorhabditis elegans)
Secernentea gar-1 35
  • 13 (a)
gar-2 35
  • 13 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 17 (a)
-- 35
  • 17 (a)
Species where no ortholog for HRH4 was found in the sources mined by GeneCards:
  • 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
rs1000107188 -- 24,480,185(+) CTAAG(A/G)TGCTG intron-variant, downstream-variant-500B
rs1000406244 -- 24,481,112(+) GTAAG(A/G)AGAAA intron-variant
rs1000473676 -- 24,474,477(+) GGATC(C/T)ATCAA intron-variant
rs1000519267 -- 24,478,234(+) GGCTT(G/T)TCCCA intron-variant, utr-variant-3-prime
rs1000562455 -- 24,479,752(+) TTACA(C/T)CGTTT intron-variant, utr-variant-3-prime

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

Variant ID Type Subtype PubMed ID
esv2716869 CNV deletion 23290073
nsv521369 CNV gain 19592680

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

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

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)
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. 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 22 64
  2. Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis. (PMID: 20199554) Yu B. … Wan J. (Br. J. Dermatol. 2010) 3 22 46 64
  3. 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 46 64
  4. Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor. (PMID: 18452403) van Rijn R.M. … Leurs R. (Biochem. J. 2008) 3 4 22 64
  5. 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 22 64

Products for HRH4 Gene

  • Addgene plasmids for HRH4

Sources for HRH4 Gene

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