Free for academic non-profit institutions. Other users need a Commercial license

HRH3 Gene(Protein Coding)

Histamine Receptor H3

GCID:
GC20M062214
GIFtS:
64
Genes Participants
UDN Logo

Aliases for HRH3 Gene

Aliases for HRH3 Gene

  • Histamine Receptor H3 2 3 5
  • G-Protein Coupled Receptor 97 3 4
  • GPCR97 3 4
  • HH3R 3 4
  • H3R 3 4
  • G Protein-Coupled Receptor 97 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 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 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 PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HRH3 Gene

Genomics for HRH3 Gene

Products:

  1. Regulatory Element

Regulatory Elements for HRH3 Gene

Enhancers for HRH3 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around HRH3 on UCSC Golden Path with GeneCards custom track

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

Genomic Location for HRH3 Gene

Chromosome:
20
Start:
62,214,766 bp from pter
End:
62,220,278 bp from pter
Size:
5,513 bases
Orientation:
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 Structure • Gene Density

RefSeq DNA sequence for HRH3 Gene

Proteins for HRH3 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

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

    Protein Symbol:
    Q9Y5N1-HRH3_HUMAN
    Recommended name:
    Histamine H3 receptor
    Protein Accession:
    Q9Y5N1
    Secondary Accessions:
    • Q4QRI7
    • Q9GZX2
    • Q9H4K8

    Protein attributes for HRH3 Gene

    Size:
    445 amino acids
    Molecular mass:
    48671 Da
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • 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

    UniProtKB/Swiss-Prot:

neXtProt entry for HRH3 Gene

Proteomics data for HRH3 Gene at MOPED

Post-translational modifications for HRH3 Gene

  • Glycosylation at Asn 11
  • Modification sites at PhosphoSitePlus

Other Protein References for HRH3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for HRH3 Gene

Domains & Families for HRH3 Gene

Gene Families for HRH3 Gene

HGNC:
IUPHAR :

Protein Domains for HRH3 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for HRH3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9Y5N1

UniProtKB/Swiss-Prot:

HRH3_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
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

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

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:0004969 histamine receptor activity IEA --
genes like me logo Genes that share ontologies with HRH3: view

Phenotypes for HRH3 Gene

MGI mutant phenotypes for HRH3:
inferred from 6 alleles
GenomeRNAi human phenotypes for HRH3:
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

Inhibitory RNA Products

Flow Cytometry Products

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

COMPARTMENTS
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:0016021 integral component of membrane 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

Interacting Proteins for HRH3 Gene

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)
http://string-db.org/version_10/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000342560%0d%0a9606.ENSP00000330070%0d%0a9606.ENSP00000355316%0d%0a9606.ENSP00000351671%0d%0a9606.ENSP00000397181%0d%0a9606.ENSP00000333194%0d%0a
Selected Interacting proteins: ENSP00000342560 Q9Y5N1-HRH3_HUMAN for HRH3 Gene via STRING I2D

Gene Ontology (GO) - Biological Process for HRH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007269 neurotransmitter secretion TAS 10347254
GO:0007271 synaptic transmission, cholinergic IBA --
GO:0014050 negative regulation of glutamate secretion IBA --
GO:0014061 regulation of norepinephrine 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

Products:

  1. Drug

(92) 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 Phosphate Approved Pharma Target, agonist 998
Betahistine Approved Pharma Target, antagonist 16
Chlorpheniramine Approved Pharma 66
Cimetidine Approved Pharma Inhibition, Inhibitor H2 receptor antagonist, H2 antagonist, I1 agonist 68
Mirtazapine Approved Pharma Target, antagonist 88

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
(<i>R</i>)-alpha-methylhistamine
Full agonist, Agonist
(<i>S</i>)-alpha-methylhistamine
Full agonist, Agonist
[<sup>3</sup>H](<i>R</i>)-alpha-methylhistamine
Full agonist, Agonist
1-[4-(3-piperidin-1-ylpropoxy)benzyl]piperidine
Antagonist
4-(3-piperdin-1-yl-propoxy)benzonitrile
Antagonist

(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

(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
genes like me logo Genes that share compounds with HRH3: view

Transcripts for HRH3 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for HRH3 Gene

(3) REFSEQ mRNAs :
(11) Additional mRNA sequences :
(23) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for HRH3 Gene

Histamine receptor H3:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

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

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b
SP1: -
SP2: - -
SP3: -
SP4:

Relevant External Links for HRH3 Gene

GeneLoc Exon Structure for
HRH3
ECgene alternative splicing isoforms for
HRH3

Expression for HRH3 Gene

Products:

  1. Primer

mRNA expression in normal human tissues for HRH3 Gene

mRNA expression in normal human tissues for HRH3 Gene
mRNA expression by BioGPS for HRH3 GenemRNA expression by GTEx 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).

SOURCE GeneReport for Unigene cluster for HRH3 Gene Hs.251399

mRNA Expression by UniProt/SwissProt for HRH3 Gene

Q9Y5N1-HRH3_HUMAN
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 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 and Protein tissue co-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
cow
(Bos Taurus)
 Mammalia HRH3 35
  • 88.67 (n)
  • 91.16 (a)
HRH3 36
  • 92 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia HRH3 35
  • 90.25 (n)
  • 93.04 (a)
HRH3 36
  • 92 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Hrh3 35
  • 87.49 (n)
  • 92.36 (a)
Hrh3 16
Hrh3 36
  • 94 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Hrh3 35
  • 87.34 (n)
  • 91.91 (a)
oppossum
(Monodelphis domestica)
 Mammalia HRH3 36
  • 80 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia HRH3 36
  • 73 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia HRH3 36
  • 98 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves HRH3 35
  • 69.88 (n)
  • 74.48 (a)
HRH3 36
  • 67 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia HRH3 36
  • 66 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia hrh3 35
  • 67.16 (n)
  • 65.26 (a)
Str.4253 35
zebrafish
(Danio rerio)
 Actinopterygii LOC100334962 35
  • 69.4 (n)
  • 74.02 (a)
hrh3 36
  • 48 (a)
 OneToOne
fruit fly
(Drosophila melanogaster)
 Insecta CG7918 36
  • 12 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea gar-1 36
  • 13 (a)
 ManyToMany
gar-2 36
  • 15 (a)
 ManyToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 36
  • 18 (a)
 ManyToMany
-- 36
  • 20 (a)
 ManyToMany
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

ENSEMBL:
Gene Tree for HRH3 (if available)
TreeFam:
Gene Tree for HRH3 (if available)

Paralogs for HRH3 Gene

Paralogs for HRH3 Gene

(17) SIMAP similar genes for HRH3 Gene using alignment to 7 proteins:

Pseudogenes.org 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
VAR_012235 -
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 reference, synonymous-codon
rs3746654 -- 62,215,106(+) TGGAC(C/T)GCCCC utr-variant-3-prime

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

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)
HRH3

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

Disorders for HRH3 Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
hepatic coma
  • hepatocerebral intoxication
central nervous system disease
  • central nervous system diseases
schizophrenia
  • schizophrenia 12
parkinson disease, late-onset
  • parkinson disease
- 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)
HRH3
Human Genome Epidemiology (HuGE) Navigator
HRH3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HRH3
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 23 67
  2. An investigation of the absolute configuration of the potent histamine H3 receptor antagonist GT-2331 using vibrational circular dichroism. (PMID: 17575572) Minick D.J. … Miller L.A. (Chirality 2007) 23 25 26
  3. [The histamine H3 receptor: a new target for the treatment of arousal and cognitive disorders]. (PMID: 17652997) Arrang J.M. (Ann Pharm Fr 2007) 23 25 26
  4. Multiple enzyme inhibitions by histamine H3 receptor antagonists as potential procognitive agents. (PMID: 16599255) Petroianu G. … Stark H. (Pharmazie 2006) 23 25 26
  5. Effects of betahistine at histamine H3 receptors: mixed inverse agonism/agonism in vitro and partial inverse agonism in vivo. (PMID: 20530654) Gbahou F. … Arrang J.M. (J. Pharmacol. Exp. Ther. 2010) 25 26

Products for HRH3 Gene

Sources for HRH3 Gene

Content