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Aliases for HRH3 Gene

Aliases for HRH3 Gene

  • Histamine Receptor H3 2 3
  • GPCR97 3 4 6
  • G-Protein Coupled Receptor 97 3 4
  • HH3R 3 4
  • H3R 3 4
  • G Protein-Coupled Receptor 97 3
  • Histamine H3 Receptor 3

External Ids for HRH3 Gene

Previous GeneCards Identifiers for HRH3 Gene

  • GC20M060553
  • GC20M061428
  • GC20M061475
  • GC20M060223
  • GC20M060790
  • GC20M057566

Summaries for HRH3 Gene

Entrez Gene Summary for HRH3 Gene

  • Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. This gene encodes one of the histamine receptors (H3) which belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and can regulate neurotransmitter release. This receptor can also increase voltage-dependent calcium current in smooth muscles and innervates the blood vessels and the heart in cardiovascular system. [provided by RefSeq, Jul 2008]

GeneCards Summary for HRH3 Gene

HRH3 (Histamine Receptor H3) is a Protein Coding gene. Diseases associated with HRH3 include hepatic coma and sleep disorder. Among its related pathways are Signaling by GPCR and Signaling by GPCR. GO annotations related to this gene include histamine receptor activity. An important paralog of this gene is CHRM4.

UniProtKB/Swiss-Prot for HRH3 Gene

  • The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization

Tocris Summary for HRH3 Gene

  • Histamine H3 receptors are Galphai/o-protein-coupled receptors first cloned in 1999. H3 receptors are expressed at high levels on histaminergic neurons in the central nervous system, particularly in the basal ganglia, cortex, hippocampus and strial area. They are expressed in the periphery at lower densities in the gastrointestinal, bronchial and cardiovascular systems. H3 receptors are thought to function as presynaptic autoreceptors, and activation stimulates the negative feedback mechanism that reduces central histaminergic activity. These receptors have displayed heterogeneity in binding and functional studies, suggesting multiple subtypes. In rats, three H3 receptor subtypes have been indentified and they all vary in the length of the third extracellular loop, have distinct CNS localization and differentially couple to adenylyl cyclase and MAPK signaling pathways. H3 receptors have multiple functions including roles in cognition, sleep-wake status, energy homeostasis regulation and inflammation. Activation of these receptors can inhibit histamine, dopamine, serotonin, noradrenalin and acetylcholine release and they participate in control of neurogenic inflammation through local-neuron feedback loops. Furthermore, H3 receptor activation increases antigen-presenting cell capacity. H3 receptors are thought to have pathophysiological relevance and are involved in cognitive impairment, seizures and possibly metabolic syndrome. The human gene encoding this receptor is localized to chromosome 20q13.33.

Gene Wiki entry for HRH3 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HRH3 Gene

Genomics for HRH3 Gene

Regulatory Elements for HRH3 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for HRH3 Gene

62,214,961 bp from pter
62,220,267 bp from pter
5,307 bases
Minus strand

Genomic View for HRH3 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for HRH3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HRH3 Gene

Proteins for HRH3 Gene

  • Protein details for HRH3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Histamine H3 receptor
    Protein Accession:
    Secondary Accessions:
    • Q4QRI7
    • Q9GZX2
    • Q9H4K8

    Protein attributes for HRH3 Gene

    445 amino acids
    Molecular mass:
    48671 Da
    Quaternary structure:
    No Data Available
    • Does not bind to cimetidine and tripolidine. Shows modest affinity for thioperamide, imetit, N-alpha-methylhistamine and R(-)-alpha-methylhistamine. Isoform 4 is unable to bind to iodoproxyfan while isoforms 1 and 3 bind it with high affinity

    Alternative splice isoforms for HRH3 Gene

neXtProt entry for HRH3 Gene

Proteomics data for HRH3 Gene at MOPED

Post-translational modifications for HRH3 Gene

  • Glycosylation at Asn11
  • Modification sites at PhosphoSitePlus

Other Protein References for HRH3 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for HRH3 Gene

Domains for HRH3 Gene

Gene Families for HRH3 Gene

Protein Domains for HRH3 Gene

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 HRH3: view

Function for HRH3 Gene

Molecular function for HRH3 Gene

UniProtKB/Swiss-Prot Function:
The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization

Gene Ontology (GO) - Molecular Function for HRH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G-protein coupled receptor activity --
GO:0004969 histamine receptor activity IEA --
GO:0008144 drug binding IEA --
GO:0051381 histamine binding IBA --
genes like me logo Genes that share ontologies with HRH3: view
genes like me logo Genes that share phenotypes with HRH3: view

Animal Models for HRH3 Gene

MGI Knock Outs for HRH3:

Animal Model Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for HRH3

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targeting and HOMER Transcription for HRH3 Gene

Localization for HRH3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HRH3 Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

Jensen Localization Image for HRH3 Gene COMPARTMENTS Subcellular localization image for HRH3 gene
Compartment Confidence
plasma membrane 5
nucleus 1

Gene Ontology (GO) - Cellular Components for HRH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 10347254
GO:0016021 integral component of membrane --
GO:0043005 neuron projection IEA --
GO:0043209 myelin sheath IEA --
genes like me logo Genes that share ontologies with HRH3: view

Pathways for HRH3 Gene

genes like me logo Genes that share pathways with HRH3: view

Pathways by source for HRH3 Gene

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

Interacting Proteins for HRH3 Gene

Gene Ontology (GO) - Biological Process for HRH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007186 G-protein coupled receptor signaling pathway --
GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger TAS 10347254
GO:0007194 negative regulation of adenylate cyclase activity IBA --
GO:0007204 positive regulation of cytosolic calcium ion concentration IEA --
GO:0007269 neurotransmitter secretion TAS 10347254
genes like me logo Genes that share ontologies with HRH3: view

Compounds for HRH3 Gene

(4) Drugbank Compounds for HRH3 Gene

Compound Status Synonyms Cas Number PubChem ID Type Actions PubMed IDs
  • [2-(2-Pyridyl)ethyl]methylamine
5638-76-6 2366 Target antagonist approved
Histamine Phosphate
  • 4-(2-Aminoethyl)imidazole bis(dihydrogen phosphate)
51-74-1 65513 Target agonist approved
  • 1,2,3,4,10,14b-Hexahydro-2-methylpyrazino(2,1-a)pyrido(2,3-c)benzazepine
61337-67-5 4205 Target antagonist approved
Target investigational

(5) Tocris Compounds for HRH3 Gene

Compound Action Cas Number
(R)-(-)-alpha-Methylhistamine dihydrobromide Potent, standard H3 agonist [868698-49-1]
BF 2649 hydrochloride H3 receptor inverse agonist/antagonist [903576-44-3]
Clobenpropit dihydrobromide Highly potent H3 antagonist and H4 partial agonist [145231-35-2]
Immepip dihydrobromide Standard H3 agonist. Also H4 agonist [164391-47-3]
JNJ 10181457 dihydrochloride H3 antagonist [544707-20-2]

(38) ApexBio Compounds for HRH3 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]

(2) HMDB Compounds for HRH3 Gene

Compound Synonyms Cas Number PubMed IDs
  • Ca
  • 1H-Imidazole-4-ethanamine

(38) IUPHAR Ligand for HRH3 Gene

Ligand Type Action Affinity Pubmed IDs
[123I]iodoproxyfan Antagonist Antagonist 10.2
iodoproxyfan Agonist Full agonist 10
immepip Agonist Full agonist 9.7
imetit Agonist Full agonist 9.7
A-349821 Antagonist Inverse agonist 9.4
N-methylhistamine Agonist Full agonist 9.3
(R)-alpha-methylhistamine Agonist Full agonist 9.2
1-[4-(3-piperidin-1-ylpropoxy)benzyl]piperidine Antagonist Antagonist 9.2
[3H](R)-alpha-methylhistamine Agonist Full agonist 9.2
N-[3H]methylhistamine Agonist Full agonist 9.1
immethridine Agonist Full agonist 9.1
methimepip Agonist Full agonist 9
FUB 349 Antagonist Antagonist 8.7
iodophenpropit Antagonist Antagonist 8.7
GR 175737 Agonist Partial agonist 8.6
proxyfan Antagonist Antagonist 8.6
Perceptinreg Agonist Full agonist 8.6
VUF 8328 Agonist Partial agonist 8.5
A331440 Antagonist Antagonist 8.5
imbutamine Agonist Full agonist 8.4
histamine Agonist Full agonist 8.3
impentamine Antagonist Antagonist 8.3
[3H]histamine Agonist Full agonist 8
VUF 4904 Antagonist Antagonist 7.9
VUF 5207 Agonist Full agonist 7.8
thioperamide Antagonist Antagonist 7.7
(S)-alpha-methylhistamine Agonist Full agonist 7.6
4-(3-piperdin-1-yl-propoxy)benzonitrile Antagonist Antagonist 7.6
ciproxifan Antagonist Antagonist 7.3
JB 98064 Antagonist Antagonist 7.3
impromidine Agonist Full agonist 7.2
A-317920 Antagonist Antagonist 7
GT2394 Antagonist Antagonist 6.4
dimaprit Agonist Full agonist 6.1
A-304121 Antagonist Antagonist 6.1
burimamide Agonist Full agonist 5.7
ABT-239 Antagonist Inverse agonist 5.2
clobenpropit Antagonist Antagonist 5.2

(28) Novoseek inferred chemical compound relationships for HRH3 Gene

Compound -log(P) Hits PubMed IDs
thioperamide 94.4 8
imetit 93.6 3
clobenpropit 89.3 2
immepip 86.6 5
histamine 86.4 87
genes like me logo Genes that share compounds with HRH3: view

Transcripts for HRH3 Gene

Unigene Clusters for HRH3 Gene

Histamine receptor H3:
Representative Sequences:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for HRH3

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for HRH3 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b
SP1: -
SP2: - -
SP3: -

Relevant External Links for HRH3 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HRH3 Gene

mRNA expression in normal human tissues for HRH3 Gene

mRNA differential expression in normal tissues according to GTEx for HRH3 Gene

This gene is overexpressed in Brain - Putamen (basal ganglia) (9.2), Brain - Nucleus accumbens (basal ganglia) (8.4), Brain - Caudate (basal ganglia) (6.4), Brain - Hypothalamus (4.9), and Brain - Cerebellum (4.8).

SOURCE GeneReport for Unigene cluster for HRH3 Gene Hs.251399

mRNA Expression by UniProt/SwissProt for HRH3 Gene

Tissue specificity: Expressed predominantly in the CNS, with the greatest expression in the thalamus and caudate nucleus. The various isoforms are mainly coexpressed in brain, but their relative expression level varies in a region-specific manner. Isoform 3 and isoform 7 are highly expressed in the thalamus, caudate nucleus and cerebellum while isoform 5 and isoform 6 show a poor expression. Isoform 5 and isoform 6 show a high expression in the amygdala, substantia nigra, cerebral cortex and hypothalamus. Isoform 7 is not found in hypothalamus or substantia nigra
genes like me logo Genes that share expressions with HRH3: 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 , Protein expression and Expression partners for HRH3 Gene

Orthologs for HRH3 Gene

This gene was present in the common ancestor of animals.

Orthologs for HRH3 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia HRH3 35
  • 88.67 (n)
  • 91.16 (a)
HRH3 36
  • 92 (a)
(Canis familiaris)
Mammalia HRH3 35
  • 90.25 (n)
  • 93.04 (a)
HRH3 36
  • 92 (a)
(Mus musculus)
Mammalia Hrh3 35
  • 87.49 (n)
  • 92.36 (a)
Hrh3 16
Hrh3 36
  • 94 (a)
(Rattus norvegicus)
Mammalia Hrh3 35
  • 87.34 (n)
  • 91.91 (a)
(Monodelphis domestica)
Mammalia HRH3 36
  • 80 (a)
(Ornithorhynchus anatinus)
Mammalia HRH3 36
  • 73 (a)
(Pan troglodytes)
Mammalia HRH3 36
  • 98 (a)
(Gallus gallus)
Aves HRH3 35
  • 69.88 (n)
  • 74.48 (a)
HRH3 36
  • 67 (a)
(Anolis carolinensis)
Reptilia HRH3 36
  • 66 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia hrh3 35
  • 67.16 (n)
  • 65.26 (a)
Str.4253 35
(Danio rerio)
Actinopterygii LOC100334962 35
  • 69.4 (n)
  • 74.02 (a)
hrh3 36
  • 48 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG7918 36
  • 12 (a)
(Caenorhabditis elegans)
Secernentea gar-1 36
  • 13 (a)
gar-2 36
  • 15 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 18 (a)
-- 36
  • 20 (a)
Species with no ortholog for HRH3:
  • 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)
  • wheat (Triticum aestivum)

Evolution for HRH3 Gene

Gene Tree for HRH3 (if available)
Gene Tree for HRH3 (if available)

Paralogs for HRH3 Gene

Paralogs for HRH3 Gene Pseudogenes for HRH3 Gene

genes like me logo Genes that share paralogs with HRH3: view

Variants for HRH3 Gene

Sequence variations from dbSNP and Humsavar for HRH3 Gene

SNP ID Clin Chr 20 pos Sequence Context AA Info Type MAF
rs1739583 -- 62,216,973(-) CCCAG(C/T)CCAAT intron-variant
rs1739585 -- 62,215,000(-) GCAAA(A/C)CGTGA utr-variant-3-prime
rs2067476 -- 62,216,129(-) AACTC(A/G)GCTGT synonymous-codon, reference
rs3746654 -- 62,215,106(+) TGGAC(C/T)GCCCC utr-variant-3-prime
rs3746655 -- 62,219,504(+) CTTCC(C/T)GGGGA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for HRH3 Gene

Variant ID Type Subtype PubMed ID
dgv4597n71 CNV Loss 21882294
dgv4598n71 CNV Loss 21882294
dgv4599n71 CNV Loss 21882294
nsv913040 CNV Loss 21882294
dgv4600n71 CNV Loss 21882294
dgv4601n71 CNV Loss 21882294
nsv518296 CNV Loss 19592680
nsv913047 CNV Loss 21882294
esv2422398 CNV Duplication 17116639
nsv470556 CNV Loss 18288195

Relevant External Links for HRH3 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HRH3 Gene

Disorders for HRH3 Gene

MalaCards: The human disease database

MalaCards: The human disease database.

Search for HRH3 Gene in MalaCards »

(3) Diseases for HRH3 Gene

(2) University of Copenhagen DISEASES for HRH3 Gene

(16) Novoseek inferred disease relationships for HRH3 Gene

Disease -log(P) Hits PubMed IDs
cognitive disorder 68 6
cns diseases 40.5 3
attention-deficit hyperactivity disorder 36.7 1
schizophrenia 35.7 6
catalepsy 25.1 1

Relevant External Links for HRH3

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with HRH3: view

No data available for OMIM , UniProtKB/Swiss-Prot and Genatlas for HRH3 Gene

Publications for HRH3 Gene

  1. Cloning and functional expression of the human histamine H3 receptor. (PMID: 10347254) Lovenberg T.W. … Erlander M.G. (Mol. Pharmacol. 1999) 2 3 4 23
  2. Molecular cloning and characterization of a new human histamine receptor, HH4R. (PMID: 11118334) Nakamura T. … Tanaka K. (Biochem. Biophys. Res. Commun. 2000) 3 4 23
  3. Structure of the human histamine H3 receptor gene (HRH3) and identification of naturally occurring variations. (PMID: 11956964) Wiedemann P. … Bruess M. (J. Neural Transm. 2002) 3 4 23
  4. Histamine H3 receptors--general characterization and their function in the cardiovascular system. (PMID: 9670104) Malinowska B. … Schlicker E. (J. Physiol. Pharmacol. 1998) 3 23
  5. Increased concentrations of histamine and its metabolite, tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma. (PMID: 12971961) Lozeva V. … Butterworth R.F. (J. Hepatol. 2003) 3 23

Products for HRH3 Gene

Sources for HRH3 Gene

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