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    HRH4 histamine receptor H4 [ Homo sapiens (human) ]

    Gene ID: 59340, updated on 11-Apr-2024

    Summary

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    Official Symbol
    HRH4provided by HGNC
    Official Full Name
    histamine receptor H4provided by HGNC
    Primary source
    HGNC:HGNC:17383
    See related
    Ensembl:ENSG00000134489 MIM:606792; AllianceGenome:HGNC:17383
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    H4; H4R; BG26; HH4R; AXOR35; GPRv53; GPCR105
    Summary
    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]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    18q11.2
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (24460637..24479974)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (24654947..24674284)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (22040601..22059938)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene oxysterol binding protein like 1A Neighboring gene uncharacterized LOC124904268 Neighboring gene Sharpr-MPRA regulatory region 8214 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:21964078-21964578 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:21964579-21965079 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9364 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:22005698-22006612 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:22006613-22007527 Neighboring gene MPRA-validated peak3074 silencer Neighboring gene impact RWD domain protein Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:22052464-22052964 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9367 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13172 Neighboring gene uncharacterized LOC105372026 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9368 Neighboring gene zinc finger protein 470 pseudogene Neighboring gene eukaryotic translation initiation factor 4A3 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Histamine H4 Receptor Expression in Triple-negative Breast Cancer: An Exploratory Study. Speisky D, et al. J Histochem Cytochem, 2022 Apr. PMID 35227109, Free PMC Article
    2. Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma. Clauzure M, et al. Int J Mol Sci, 2022 Jan 26. PMID 35163302, Free PMC Article
    3. Histamine-4 Receptor: Emerging Target for the Treatment of Neurological Diseases. Shan L, et al. Curr Top Behav Neurosci, 2022. PMID 34432256
    4. Histamine H4 receptor gene polymorphisms: a potential contributor to Meniere disease. Qin D, et al. BMC Med Genomics, 2019 May 27. PMID 31133025, Free PMC Article
    5. Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase. Mauro E, et al. Nucleic Acids Res, 2019 Apr 23. PMID 30767014, Free PMC Article

    See all (103) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Histamine H1- and H4-receptor expression in human colon-derived cell lines.
      Title: Histamine H(1)- and H(4)-receptor expression in human colon-derived cell lines.
    2. Histamine-4 Receptor: Emerging Target for the Treatment of Neurological Diseases.
      Title: Histamine-4 Receptor: Emerging Target for the Treatment of Neurological Diseases.
    3. Unraveling the venom chemistry with evidence for histamine as key regulator in the envenomation by caterpillar Automeris zaruma.
      Title: Unraveling the venom chemistry with evidence for histamine as key regulator in the envenomation by caterpillar Automeris zaruma.
    4. Histamine H4 Receptor Expression in Triple-negative Breast Cancer: An Exploratory Study.
      Title: Histamine H4 Receptor Expression in Triple-negative Breast Cancer: An Exploratory Study.
    5. Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma.
      Title: Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma.
    6. Identification of TSPAN4 as Novel Histamine H4 Receptor Interactor.
      Title: Identification of TSPAN4 as Novel Histamine H(4) Receptor Interactor.
    7. Study of the antitumour effects and the modulation of immune response by histamine in breast cancer.
      Title: Study of the antitumour effects and the modulation of immune response by histamine in breast cancer.
    8. HRH4 rs77485247 polymorphism may be an important mediator in regulating proinflammatory cytokines
      Title: Histamine H4 receptor gene polymorphisms: a potential contributor to Meniere disease.
    9. our present study confirmed the expression of H4R in ESCC, which was closely associated with clinicopathological features, including histological grades, primary tumor size, lymph node metastasis, and patient survival.
      Title: Activation of histamine H(4) receptor suppresses the proliferation and invasion of esophageal squamous cell carcinoma via both metabolism and non-metabolism signaling pathways.
    10. ur data indicate that the H4 peptide tail promotes the formation of active strand transfer complexes (STCs) and support an activation step of the incoming intasome at the contact of the histone tail.
      Title: Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase.
    Submit: New GeneRIF Correction See all GeneRIFs (90)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genetic association with overall survival of taxane-treated lung cancer patients - A genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC133027

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables G protein-coupled acetylcholine receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables G protein-coupled serotonin receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables histamine receptor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in G protein-coupled serotonin receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in biological_process ND
    No biological Data available
    more info
    		  
    involved_in chemical synaptic transmission IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in inflammatory response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of cytosolic calcium ion concentration IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in dendrite IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in synapse IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    histamine H4 receptor
    Names
    G-protein coupled receptor 105
    SP9144
    pfi-013

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001143828.2 → NP_001137300.1  histamine H4 receptor isoform 2

      See identical proteins and their annotated locations for NP_001137300.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has multiple differences in the coding region but maintains the reading frame, compared to variant 1. This variant encodes isoform 2, also known as H4R(302), which is shorter than isoform 1.
      Source sequence(s)
      AC007922, AF312230, BC069136, DQ835186
      Consensus CDS
      CCDS45841.1
      UniProtKB/Swiss-Prot
      Q9H3N8
      Related
      ENSP00000402526.2, ENST00000426880.2
      Conserved Domains (1) summary
      pfam00001
      Location:211 → 270
      7tm_1; 7 transmembrane receptor (rhodopsin family)

    2. NM_001160166.2 → NP_001153638.1  histamine H4 receptor isoform 3

      See identical proteins and their annotated locations for NP_001153638.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate coding exon resulting in a frameshift, compared to variant 1. The resulting isoform (3), also known as H4R(67), has a substantially shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC007922, AF312230, BC069136, DQ835187
      UniProtKB/TrEMBL
      B2KJ49
      Conserved Domains (2) summary
      cd14964
      Location:18 → 42
      7tm_GPCRs; TM helix 1 [structural motif]
      cl28897
      Location:16 → 67
      7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily

    3. NM_021624.4 → NP_067637.2  histamine H4 receptor isoform 1

      See identical proteins and their annotated locations for NP_067637.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC007922, AF312230
      Consensus CDS
      CCDS11887.1
      UniProtKB/Swiss-Prot
      B0YJ19, B2KJ48, Q4G0I6, Q9GZQ0, Q9H3N8
      UniProtKB/TrEMBL
      Q96LD9
      Related
      ENSP00000256906.4, ENST00000256906.5
      Conserved Domains (1) summary
      cd15295
      Location:16 → 374
      7tmA_Histamine_H4R; histamine receptor subtype H4R, member of the class A family of seven-transmembrane G protein-coupled receptors

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

      Range
      24460637..24479974
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060942.1 Alternate T2T-CHM13v2.0

      Range
      24654947..24674284
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H3N8.2 GenPept UniProtKB/Swiss-Prot:Q9H3N8

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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