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Aliases for HRH3 Gene

Aliases for HRH3 Gene

  • Histamine Receptor H3 2 3 5
  • GPCR97 3 4
  • HH3R 3 4
  • H3R 3 4
  • G Protein-Coupled Receptor 97 3
  • G-Protein Coupled Receptor 97 4
  • 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 Central Nervous System Disease. Among its related pathways are Peptide ligand-binding receptors and Monoamine Transport. GO annotations related to this gene include G-protein coupled receptor activity and histamine receptor activity. An important paralog of this gene is HRH4.

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 expressed at high levels on histaminergic neurons in the CNS, particularly in the basal ganglia, cortex and hippocampus. H3 receptors are thought to function as presynaptic autoreceptors.

Gene Wiki entry for HRH3 Gene

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

Genomics for HRH3 Gene

Regulatory Elements for HRH3 Gene

Enhancers for HRH3 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
GH20G062245 1 ENCODE dbSUPER 12.3 -26.5 -26495 1.7 SOX13 MXI1 ESRRA SAP130 ZFP64 ARID4B MAX RARA TEAD3 SCRT2 HRH3 LAMA5-AS1 MTG2 ENSG00000226332 OSBPL2 GC20M062290
GH20G062186 0.9 Ensembl ENCODE 11.7 +32.8 32790 1.4 SCRT1 HLF PAX8 EGR1 IKZF1 SCRT2 FOS ZNF24 MAFK SPI1 PSMA7 SS18L1 HRH3 MTG2 PIR52239
GH20G062240 0.8 Ensembl ENCODE 12.7 -21.9 -21858 2.6 ZNF263 SIN3A ZBTB33 KDM1A NFE2 NR2F2 HRH3 OSBPL2 LAMA5-AS1 GC20M062290
GH20G062010 0.9 ENCODE 10.6 +209.2 209249 0.2 ELF3 ARID4B SIN3A DMAP1 ZNF48 RAD21 ZNF143 ZNF654 MXD4 USF2 PSMA7 SS18L1 HRH3 CDH4 LOC105372704 GC20M062040
GH20G062287 0.8 dbSUPER 11.2 -68.4 -68390 2.3 HDGF PKNOX1 SUZ12 NFIB BMI1 ZBTB7B ZKSCAN1 ZFHX2 ARID3A CTBP1 LAMA5 HRH3 ENSG00000226332 LAMA5-AS1 ADRM1 GC20M062290 OSBPL2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around HRH3 on UCSC Golden Path with GeneCards custom track

Promoters for HRH3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

Genomic Location for HRH3 Gene

62,214,766 bp from pter
62,220,278 bp from pter
5,513 bases
Minus strand

Genomic View for HRH3 Gene

Genes around HRH3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HRH3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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

Post-translational modifications for HRH3 Gene

  • Glycosylation at isoforms=2, 3, 4, 5, 6, 711
  • Modification sites at PhosphoSitePlus

Other Protein References for HRH3 Gene

No data available for DME Specific Peptides for HRH3 Gene

Domains & Families 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:0004871 signal transducer activity IEA --
GO:0004930 G-protein coupled receptor activity IEA --
GO:0004969 histamine receptor activity IEA --
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

  • Taconic Biosciences Mouse Models for HRH3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets 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

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 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:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0098793 presynapse IEA --
genes like me logo Genes that share ontologies with HRH3: view

Pathways & Interactions for HRH3 Gene

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

Gene Ontology (GO) - Biological Process for HRH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction IEA --
GO:0007186 G-protein coupled receptor signaling pathway IEA --
GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger TAS 10347254
GO:0007269 neurotransmitter secretion TAS 10347254
GO:0014050 negative regulation of glutamate secretion IBA --
genes like me logo Genes that share ontologies with HRH3: view

No data available for SIGNOR curated interactions for HRH3 Gene

Drugs & Compounds for HRH3 Gene

(101) Drugs for HRH3 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
Betahistine Approved Pharma Target, antagonist 16
Cimetidine Approved Pharma Inhibition, Inhibitor H2 receptor antagonist, H2 antagonist, I1 agonist 75
Mirtazapine Approved Pharma Target, antagonist 90
Risperidone Approved, Investigational Pharma Antagonist SR-2A inhibitor 492

(18) Additional Compounds for HRH3 Gene - From: Novoseek, IUPHAR, and Tocris

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

(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
Immethridine dihydrobromide Potent H3 agonist, highly selective over H4 699020-93-4
JNJ 5207852 dihydrochloride High affinity H3 receptor antagonist 398473-34-2

(44) ApexBio Compounds for HRH3 Gene

Compound Action Cas Number
A 331440 dihydrochloride H3 receptor antagonist,non-imidazole,high affinity 1049740-32-0
Astemizole 68844-77-9
Azatadine dimaleate 3978-86-7
Azelastine HCl 79307-93-0
Bavisant Human H3 receptor antagonist 929622-08-2
Bavisant dihydrochloride Human H3 receptor antagonist 929622-09-3
Bavisant dihydrochloride hydrate Human H3 receptor antagonist 1103522-80-0
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
Clemizole hydrochloride H1 histamine receptor antagonist 1163-36-6
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 HRH3: view

Transcripts for HRH3 Gene

mRNA/cDNA for HRH3 Gene

Unigene Clusters for HRH3 Gene

Histamine receptor H3:
Representative Sequences:

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 from GTEx, Illumina, BioGPS, and CGAP SAGE for HRH3 Gene

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

This gene is overexpressed in Brain - Putamen (basal ganglia) (x9.2), Brain - Nucleus accumbens (basal ganglia) (x8.4), Brain - Caudate (basal ganglia) (x6.4), Brain - Hypothalamus (x4.9), and Brain - Cerebellum (x4.8).

NURSA nuclear receptor signaling pathways regulating expression of HRH3 Gene:


SOURCE GeneReport for Unigene cluster for HRH3 Gene:


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.

Evidence on tissue expression from TISSUES for HRH3 Gene

  • Nervous system(4.6)
  • Blood(4.2)
genes like me logo Genes that share expression patterns with HRH3: 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 expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer 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
(Pan troglodytes)
Mammalia HRH3 35
  • 98 (a)
(Canis familiaris)
Mammalia HRH3 34 35
  • 90.25 (n)
(Bos Taurus)
Mammalia HRH3 34 35
  • 88.67 (n)
(Mus musculus)
Mammalia Hrh3 34 16 35
  • 87.49 (n)
(Rattus norvegicus)
Mammalia Hrh3 34
  • 87.34 (n)
(Monodelphis domestica)
Mammalia HRH3 35
  • 80 (a)
(Ornithorhynchus anatinus)
Mammalia HRH3 35
  • 73 (a)
(Gallus gallus)
Aves HRH3 34 35
  • 69.88 (n)
(Anolis carolinensis)
Reptilia HRH3 35
  • 66 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia hrh3 34
  • 67.16 (n)
Str.4253 34
(Danio rerio)
Actinopterygii LOC100334962 34
  • 69.4 (n)
hrh3 35
  • 48 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG7918 35
  • 12 (a)
(Caenorhabditis elegans)
Secernentea gar-2 35
  • 15 (a)
gar-1 35
  • 13 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 20 (a)
-- 35
  • 18 (a)
Species where no ortholog for HRH3 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)
  • 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
rs1000467386 -- 62,220,705(+) GGGTC(G/T)CCGGG upstream-variant-2KB
rs1000735503 -- 62,220,964(+) AGGCT(A/G)AGGAG upstream-variant-2KB
rs1000839224 -- 62,220,551(+) TTCCC(A/G)TGCCC upstream-variant-2KB
rs1001202932 -- 62,214,926(+) AGCAC(A/G/T)AAGGC downstream-variant-500B, utr-variant-3-prime
rs1001209005 -- 62,222,012(+) GGGTG(A/G)GGGTT upstream-variant-2KB

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

Variant ID Type Subtype PubMed ID
esv2422398 CNV duplication 17116639
nsv1160689 CNV deletion 26073780
nsv470556 CNV loss 18288195
nsv518296 CNV loss 19592680
nsv955149 CNV deletion 24416366

Variation tolerance for HRH3 Gene

Residual Variation Intolerance Score: 33.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.93; 19.29% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HRH3 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 HRH3 Gene

Disorders for HRH3 Gene

MalaCards: The human disease database

(3) MalaCards diseases for HRH3 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hepatic coma
  • hepatocerebral intoxication
central nervous system disease
  • cns
  • schizophrenia 12
- elite association - COSMIC cancer census association via MalaCards
Search HRH3 in MalaCards View complete list of genes associated with diseases

Relevant External Links for HRH3

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 HRH3: view

No data available for 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 22 64
  2. 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 22 64
  3. Molecular cloning and characterization of a new human histamine receptor, HH4R. (PMID: 11118334) Nakamura T. … Tanaka K. (Biochem. Biophys. Res. Commun. 2000) 3 4 22 64
  4. Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol? (PMID: 20602615) RuaA+o G. … Wu A.H. (Pharmacogenomics 2010) 3 46 64
  5. Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone. (PMID: 18996102) RuaA+o G. … Hanks S. (Clin. Chim. Acta 2009) 3 46 64

Products for HRH3 Gene

Sources for HRH3 Gene

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