Human Gene HRH4 (uc002kvi.3) Description and Page Index
  Description: Homo sapiens histamine receptor H4 (HRH4), transcript variant 1, mRNA.
RefSeq Summary (NM_021624): 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].
Transcript (Including UTRs)
   Position: hg19 chr18:22,040,593-22,059,921 Size: 19,329 Total Exon Count: 3 Strand: +
Coding Region
   Position: hg19 chr18:22,040,693-22,057,526 Size: 16,834 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr18:22,040,593-22,059,921)mRNA (may differ from genome)Protein (390 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Histamine H4 receptor; Short=H4R; Short=HH4R; AltName: Full=AXOR35; AltName: Full=G-protein coupled receptor 105; AltName: Full=GPRv53; AltName: Full=Pfi-013; AltName: Full=SP9144;
FUNCTION: The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
TISSUE SPECIFICITY: Expressed primarily in the bone marrow and eosinophils. Shows preferential distribution in cells of immunological relevance such as T-cells, dendritic cells, monocytes, mast cells, neutrophils. Also expressed in a wide variety of peripheral tissues, including the heart, kidney, liver, lung, pancreas, skeletal muscle, prostate, small intestine, spleen, testis, colon, fetal liver and lymph node.
INDUCTION: Expression is either up-regulated or down-regulated upon activation of the lymphoid tissues and this regulation may depend on the presence of IL10/interleukin-10 or IL13/interleukin- 13.
MISCELLANEOUS: Does not bind diphenhydramine, loratadine, ranitidine, cimetidine and chlorpheniramine. Shows modest affinity for dimaprit, impromidine, clobenpropit, thioperamide, burimamide clozapine, immepip and imetit. The order of inhibitory activity was imetit > clobenpropit > burimamide > thioperamide. Clobenpropit behaves as a partial agonist, dimaprit and impromidine show some agonist activity while clozapine behaves as a full agonist. Thioperamide shows inverse agonism (enhances cAMP activity). The order of inhibitory activity of histamine derivatives was Histamine > N-alpha-methylhistamine > R(-)-alpha- methylhistamine > S(+)-alpha-methylhistamine. Both N-alpha- methylhistamine > R(-)-alpha-methylhistamine behave as full agonists.
SIMILARITY: Belongs to the G-protein coupled receptor 1 family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): HRH4
CDC HuGE Published Literature: HRH4
Positive Disease Associations: Monocytes , Triglycerides
Related Studies:
  1. Monocytes
    , , . [PubMed 0]
  2. Triglycerides
    Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics. [PubMed 17903299]
    Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.

-  MalaCards Disease Associations
  MalaCards Gene Search: HRH4
Diseases sorted by gene-association score: paraneoplastic cerebellar degeneration (9), pericarditis (6), allergic hypersensitivity disease (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 0.16 RPKM in Testis
Total median expression: 1.75 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -19.10100-0.191 Picture PostScript Text
3' UTR -837.562395-0.350 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000276 - 7TM_GPCR_Rhodpsn
IPR017452 - GPCR_Rhodpsn_supfam
IPR008102 - Histamine_H4_recept

Pfam Domains:
PF00001 - 7 transmembrane receptor (rhodopsin family)
PF10320 - Serpentine type 7TM GPCR chemoreceptor Srsx

SCOP Domains:
81321 - Family A G protein-coupled receptor-like

ModBase Predicted Comparative 3D Structure on Q9H3N8
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004871 signal transducer activity
GO:0004930 G-protein coupled receptor activity
GO:0004969 histamine receptor activity

Biological Process:
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007194 negative regulation of adenylate cyclase activity
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0008150 biological_process
GO:0043408 regulation of MAPK cascade

Cellular Component:
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane

-  Descriptions from all associated GenBank mRNAs
  BC069136 - Homo sapiens histamine receptor H4, mRNA (cDNA clone MGC:95417 IMAGE:7216992), complete cds.
AF312230 - Homo sapiens histamine receptor H4 subtype mRNA, complete cds.
AB045370 - Homo sapiens mRNA for histamine H4 receptor HH4R, complete cds.
BC112348 - Homo sapiens histamine receptor H4, mRNA (cDNA clone MGC:133027 IMAGE:40006540), complete cds.
AB044934 - Homo sapiens H4R mRNA for histamine H4 receptor, complete cds.
JD402838 - Sequence 383862 from Patent EP1572962.
DQ835187 - Homo sapiens histamine H4 receptor isoform 67 mRNA, complete cds, alternatively spliced.
KJ894482 - Synthetic construct Homo sapiens clone ccsbBroadEn_03876 HRH4 gene, encodes complete protein.
AF307973 - Homo sapiens histamine H4 receptor mRNA, complete cds.
AF325356 - Homo sapiens histamine receptor H4 (AXOR35) mRNA, complete cds.
AF329449 - Homo sapiens histamine receptor H4 mRNA, complete cds.
AJ298292 - Homo sapiens mRNA for histamine receptor H4 (HRH4 gene).
AY008280 - Homo sapiens histamine receptor H4 (H4) mRNA, complete cds.
AY136745 - Homo sapiens histamine receptor H4 (HRH4) mRNA, complete cds.
DQ835186 - Homo sapiens histamine H4 receptor isoform 302 mRNA, complete cds, alternatively spliced.
JD096665 - Sequence 77689 from Patent EP1572962.
JD228186 - Sequence 209210 from Patent EP1572962.
JD171463 - Sequence 152487 from Patent EP1572962.
JD374097 - Sequence 355121 from Patent EP1572962.
JD553064 - Sequence 534088 from Patent EP1572962.
JD127374 - Sequence 108398 from Patent EP1572962.
JD411426 - Sequence 392450 from Patent EP1572962.
JD091585 - Sequence 72609 from Patent EP1572962.
JD429600 - Sequence 410624 from Patent EP1572962.
JD142789 - Sequence 123813 from Patent EP1572962.
JD095667 - Sequence 76691 from Patent EP1572962.
JD308440 - Sequence 289464 from Patent EP1572962.
JD208371 - Sequence 189395 from Patent EP1572962.
JD204921 - Sequence 185945 from Patent EP1572962.
JD486980 - Sequence 468004 from Patent EP1572962.
JD098488 - Sequence 79512 from Patent EP1572962.
JD182733 - Sequence 163757 from Patent EP1572962.
JD428152 - Sequence 409176 from Patent EP1572962.
JD064679 - Sequence 45703 from Patent EP1572962.
JD299714 - Sequence 280738 from Patent EP1572962.
JD112376 - Sequence 93400 from Patent EP1572962.
JD112377 - Sequence 93401 from Patent EP1572962.
JD542682 - Sequence 523706 from Patent EP1572962.
JD217952 - Sequence 198976 from Patent EP1572962.
JD212643 - Sequence 193667 from Patent EP1572962.
JD198021 - Sequence 179045 from Patent EP1572962.
JD198022 - Sequence 179046 from Patent EP1572962.
JD413311 - Sequence 394335 from Patent EP1572962.
JD413312 - Sequence 394336 from Patent EP1572962.
JD246788 - Sequence 227812 from Patent EP1572962.
JD246789 - Sequence 227813 from Patent EP1572962.
JD246790 - Sequence 227814 from Patent EP1572962.
JD198519 - Sequence 179543 from Patent EP1572962.
JD153377 - Sequence 134401 from Patent EP1572962.
JD161832 - Sequence 142856 from Patent EP1572962.
JD525364 - Sequence 506388 from Patent EP1572962.
JD238786 - Sequence 219810 from Patent EP1572962.
JD110438 - Sequence 91462 from Patent EP1572962.
JD367667 - Sequence 348691 from Patent EP1572962.
JD535505 - Sequence 516529 from Patent EP1572962.
JD521760 - Sequence 502784 from Patent EP1572962.
JD476866 - Sequence 457890 from Patent EP1572962.
JD332633 - Sequence 313657 from Patent EP1572962.
JD170903 - Sequence 151927 from Patent EP1572962.
JD311309 - Sequence 292333 from Patent EP1572962.
JD427879 - Sequence 408903 from Patent EP1572962.
JD265956 - Sequence 246980 from Patent EP1572962.
JD265957 - Sequence 246981 from Patent EP1572962.
JD513564 - Sequence 494588 from Patent EP1572962.
JD480078 - Sequence 461102 from Patent EP1572962.
JD334436 - Sequence 315460 from Patent EP1572962.
JD150751 - Sequence 131775 from Patent EP1572962.
JD254843 - Sequence 235867 from Patent EP1572962.
JD332750 - Sequence 313774 from Patent EP1572962.
JD564747 - Sequence 545771 from Patent EP1572962.
JD064057 - Sequence 45081 from Patent EP1572962.
JD190046 - Sequence 171070 from Patent EP1572962.
JD103505 - Sequence 84529 from Patent EP1572962.
JD308308 - Sequence 289332 from Patent EP1572962.
JD414986 - Sequence 396010 from Patent EP1572962.
JD346700 - Sequence 327724 from Patent EP1572962.
JD285022 - Sequence 266046 from Patent EP1572962.
JD300514 - Sequence 281538 from Patent EP1572962.
JD433321 - Sequence 414345 from Patent EP1572962.
JD531749 - Sequence 512773 from Patent EP1572962.
JD176231 - Sequence 157255 from Patent EP1572962.
JD272133 - Sequence 253157 from Patent EP1572962.
JD198574 - Sequence 179598 from Patent EP1572962.
JD153576 - Sequence 134600 from Patent EP1572962.
JD428251 - Sequence 409275 from Patent EP1572962.
JD428252 - Sequence 409276 from Patent EP1572962.
JD550249 - Sequence 531273 from Patent EP1572962.
JD234079 - Sequence 215103 from Patent EP1572962.
JD234080 - Sequence 215104 from Patent EP1572962.
JD293103 - Sequence 274127 from Patent EP1572962.
JD293104 - Sequence 274128 from Patent EP1572962.
JD270341 - Sequence 251365 from Patent EP1572962.
JD456690 - Sequence 437714 from Patent EP1572962.
JD121992 - Sequence 103016 from Patent EP1572962.
JD340567 - Sequence 321591 from Patent EP1572962.
JD275504 - Sequence 256528 from Patent EP1572962.
JD418219 - Sequence 399243 from Patent EP1572962.
JD414547 - Sequence 395571 from Patent EP1572962.
JD367587 - Sequence 348611 from Patent EP1572962.
JD069662 - Sequence 50686 from Patent EP1572962.
JD132277 - Sequence 113301 from Patent EP1572962.
JD071894 - Sequence 52918 from Patent EP1572962.
JD315405 - Sequence 296429 from Patent EP1572962.
JD298285 - Sequence 279309 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein Q9H3N8 (Reactome details) participates in the following event(s):

R-HSA-390886 H3 and H4 receptors binds histamine
R-HSA-749454 The Ligand:GPCR:Gi complex dissociates
R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi
R-HSA-390650 Histamine receptors
R-HSA-418594 G alpha (i) signalling events
R-HSA-375280 Amine ligand-binding receptors
R-HSA-388396 GPCR downstream signalling
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-372790 Signaling by GPCR
R-HSA-500792 GPCR ligand binding
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: B0YJ19, B2KJ48, GPCR105, HRH4_HUMAN, NM_021624, NP_067637, Q4G0I6, Q9GZQ0, Q9H3N8
UCSC ID: uc002kvi.3
RefSeq Accession: NM_021624
Protein: Q9H3N8 (aka HRH4_HUMAN or HH4R_HUMAN)
CCDS: CCDS11887.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_021624.3
exon count: 3CDS single in 3' UTR: no RNA size: 3686
ORF size: 1173CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2537.50frame shift in genome: no % Coverage: 99.51
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.