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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 Kleine-Levin Hibernation Syndrome. Among its related pathways are Peptide ligand-binding receptors and Signaling by GPCR. Gene Ontology (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

Additional gene information 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

GeneHancer (GH) Regulatory Elements for HRH3 Gene

Promoters and enhancers for HRH3 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH20I062220 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE 550.8 +0.0 31 0.5 HDAC1 NFIB ARID4B SIN3A DNMT3B ZNF48 ZSCAN9 RARA SLC30A9 ZNF766 HRH3 PIR52239
GH20I062245 Enhancer 0.9 ENCODE dbSUPER 12.3 -26.5 -26495 1.7 SOX13 MXI1 SAP130 ZNF449 ZFP64 ARID4B MAX RARA TEAD3 SCRT2 HRH3 LAMA5-AS1 MTG2 ENSG00000226332 OSBPL2 GC20M062290
GH20I062186 Enhancer 0.8 Ensembl ENCODE 11.7 +32.8 32790 1.4 SCRT1 HLF CBFA2T3 PAX8 EGR1 SCRT2 IKZF1 SPI1 PSMA7 SS18L1 HRH3 MTG2 PIR52239
GH20I062240 Enhancer 0.7 Ensembl ENCODE 12.7 -21.9 -21858 2.6 SIN3A ELF1 ZBTB33 KDM1A NFE2 NR2F2 HRH3 OSBPL2 LAMA5-AS1 GC20M062290
GH20I062010 Enhancer 0.8 ENCODE 10.6 +209.2 209248 0.2 ELF3 ARID4B SIN3A DMAP1 ZNF48 RAD21 ARID2 SMARCA5 ZNF654 USF2 PSMA7 SS18L1 HRH3 CDH4 LOC105372704 GC20M062040 TAF4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around HRH3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the HRH3 gene promoter:

Genomic Locations for HRH3 Gene

Genomic Locations for HRH3 Gene
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

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

Human Protein Atlas (HPA):
  • FDA approved drug targets
  • G-protein coupled receptors
  • Predicted membrane proteins

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 IBA,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

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for HRH3

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , 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:0045202 synapse IEA --
genes like me logo Genes that share ontologies with HRH3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HRH3 Gene

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,TAS --
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:0007269 neurotransmitter secretion TAS 10347254
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, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Histamine Approved, Investigational Pharma Full agonist, Agonist, Target, agonist 1105
Betahistine Approved, Investigational Pharma Target, antagonist 16
Cimetidine Approved, Investigational Pharma Inhibition, Inhibitor H2 receptor antagonist 81
calcium Approved Nutra 0
Mirtazapine Approved Pharma Target, antagonist 97

(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
(S)-(+)-alpha-Methylhistamine dihydrobromide H3 agonist, less active enantiomer 75614-93-6
Imetit dihydrobromide Standard H3 and H4 agonist (H3 > H4) 32385-58-3
Immepip dihydrobromide Standard H3 agonist. Also H4 agonist 164391-47-3
Nalpha-Methylhistamine dihydrochloride Non-selective H3 agonist 16503-22-3

(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

Drug Products

Transcripts for HRH3 Gene

mRNA/cDNA for HRH3 Gene

Unigene Clusters for HRH3 Gene

Histamine receptor H3:
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for HRH3

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 34
  • 98 (a)
(Canis familiaris)
Mammalia HRH3 33 34
  • 90.25 (n)
(Bos Taurus)
Mammalia HRH3 33 34
  • 88.67 (n)
(Mus musculus)
Mammalia Hrh3 33 16 34
  • 87.49 (n)
(Rattus norvegicus)
Mammalia Hrh3 33
  • 87.34 (n)
(Monodelphis domestica)
Mammalia HRH3 34
  • 80 (a)
(Ornithorhynchus anatinus)
Mammalia HRH3 34
  • 73 (a)
(Gallus gallus)
Aves HRH3 33 34
  • 69.88 (n)
(Anolis carolinensis)
Reptilia HRH3 34
  • 66 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia hrh3 33
  • 67.16 (n)
Str.4253 33
(Danio rerio)
Actinopterygii LOC100334962 33
  • 69.4 (n)
hrh3 34
  • 48 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG7918 34
  • 12 (a)
(Caenorhabditis elegans)
Secernentea gar-2 34
  • 15 (a)
gar-1 34
  • 13 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 20 (a)
-- 34
  • 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 Variation AA Info Type
rs1000467386 -- 62,220,705(-) T/G upstream_transcript_variant
rs1000735503 -- 62,220,964(-) G/A upstream_transcript_variant
rs1000839224 -- 62,220,551(-) G/A upstream_transcript_variant
rs1001202932 -- 62,214,926(-) G/A/T 3_prime_UTR_variant, downstream_transcript_variant, genic_downstream_transcript_variant
rs1001209005 -- 62,222,012(-) G/A upstream_transcript_variant

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

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

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)

Additional Variant Information 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

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

Disorder Aliases PubMed IDs
hepatic coma
  • hepatocerebral intoxication
kleine-levin hibernation syndrome
  • kleine-levin syndrome
recurrent hypersomnia
  • primary recurrent hypersomnia
central nervous system disease
  • cns
migraine with or without aura 1
  • migraine with or without aura, susceptibility to, 1
- elite association - COSMIC cancer census association via MalaCards
Search HRH3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HRH3

Genetic Association Database
Human Genome Epidemiology 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 TW … Erlander MG (Molecular pharmacology 1999) 2 3 4 22 58
  2. Structure of the human histamine H3 receptor gene (HRH3) and identification of naturally occurring variations. (PMID: 11956964) Wiedemann P … Brüss M (Journal of neural transmission (Vienna, Austria : 1996) 2002) 3 4 22 58
  3. Molecular cloning and characterization of a new human histamine receptor, HH4R. (PMID: 11118334) Nakamura T … Tanaka K (Biochemical and biophysical research communications 2000) 3 4 22 58
  4. Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol? (PMID: 20602615) Ruaño G … Wu AH (Pharmacogenomics 2010) 3 44 58
  5. Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis. (PMID: 19156168) Need AC … Goldstein DB (European journal of human genetics : EJHG 2009) 3 44 58

Products for HRH3 Gene

Sources for HRH3 Gene

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