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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
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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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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

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