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HTR4 Gene(Protein Coding)

5-Hydroxytryptamine Receptor 4

GCID:
GC05M148451
GIFtS:
67
Genes Participants
UDN Logo

Aliases for HTR4 Gene

Aliases for HTR4 Gene

  • 5-Hydroxytryptamine Receptor 4 2 3
  • 5-Hydroxytryptamine (Serotonin) Receptor 4, G Protein-Coupled 2 3 5
  • 5-HT4 3 4
  • 5-Hydroxytryptamine (Serotonin) Receptor 4 2
  • Cardiac 5-HT4 Receptor 3
  • Serotonin Receptor 4 4
  • 5-HT4R 3
  • 5-HT-4 4

External Ids for HTR4 Gene

Previous GeneCards Identifiers for HTR4 Gene

  • GC05M147904
  • GC05M148425
  • GC05M147859
  • GC05M147810
  • GC05M142977

Summaries for HTR4 Gene

Entrez Gene Summary for HTR4 Gene

  • This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described. [provided by RefSeq, May 2010]

GeneCards Summary for HTR4 Gene

HTR4 (5-Hydroxytryptamine Receptor 4) is a Protein Coding gene. Diseases associated with HTR4 include Constipation and Irritable Bowel Syndrome. Among its related pathways are Peptide ligand-binding receptors and cAMP signaling pathway. GO annotations related to this gene include G-protein coupled receptor activity and trace-amine receptor activity. An important paralog of this gene is TAAR9.

UniProtKB/Swiss-Prot for HTR4 Gene

  • This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.

Tocris Summary for HTR4 Gene

  • Serotonin 5-HT4 receptors are located primarily in nigrostriatal and mesolimbic systems and smooth muscle. The receptor plays a role in memory and learning, anxiety, visual perception and smooth muscle relaxation.

Gene Wiki entry for HTR4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HTR4 Gene

Genomics for HTR4 Gene

Products:

  1. Regulatory Element

Regulatory Elements for HTR4 Gene

Enhancers for HTR4 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 HTR4 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the HTR4 gene promoter:

Genomic Location for HTR4 Gene

Chromosome:
5
Start:
148,451,032 bp from pter
End:
148,677,235 bp from pter
Size:
226,204 bases
Orientation:
Minus strand

Genomic View for HTR4 Gene

Genes around HTR4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HTR4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HTR4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for HTR4 Gene

Proteins for HTR4 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for HTR4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13639-5HT4R_HUMAN
    Recommended name:
    5-hydroxytryptamine receptor 4
    Protein Accession:
    Q13639
    Secondary Accessions:
    • C4WYH4
    • Q546Q1
    • Q684M0
    • Q712M9
    • Q96KH9
    • Q96KI0
    • Q9H199
    • Q9NY73
    • Q9UBM6
    • Q9UBT4
    • Q9UE22
    • Q9UE23
    • Q9UQR6

    Protein attributes for HTR4 Gene

    Size:
    388 amino acids
    Molecular mass:
    43761 Da
    Quaternary structure:
    • Isoform 5-HT4(A) interacts with MAGI2, MPP3, SLC9A3R1 and SNX27 isoforms 1 and 2. Isoform 5-HT4(E) interacts with INADL, NOS1 and SEC23A. Isoform 5-HT4(A) forms a complex including SLC9A3R1 and EZR (By similarity). Interacts (via C-terminus 330-346 AA) with GRK5; this interaction is promoted by 5-HT (serotonin).

    Alternative splice isoforms for HTR4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HTR4 Gene

Proteomics data for HTR4 Gene at MOPED

Post-translational modifications for HTR4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for HTR4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for HTR4 (5-HT(4))

No data available for DME Specific Peptides for HTR4 Gene

Domains & Families for HTR4 Gene

Gene Families for HTR4 Gene

HGNC:
IUPHAR :

Protein Domains for HTR4 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for HTR4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q13639

UniProtKB/Swiss-Prot:

5HT4R_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 HTR4: view

Function for HTR4 Gene

Products:

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

Molecular function for HTR4 Gene

GENATLAS Biochemistry:
5-hydroxytryptamine (serotonin) receptor,subtype 4A,and three splice variants 4B,4C,4D,G protein coupled receptor superfamily,activating adenylate cyclase
UniProtKB/Swiss-Prot Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.

Phenotypes for HTR4 Gene

MGI mutant phenotypes for HTR4:
inferred from 2 alleles
GenomeRNAi human phenotypes for HTR4:
genes like me logo Genes that share phenotypes with HTR4: view

Animal Models for HTR4 Gene

MGI Knock Outs for HTR4:

Animal Model Products

  • Taconic Biosciences Mouse Models for HTR4

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for HTR4 Gene

Localization for HTR4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HTR4 Gene

Cell membrane; Multi-pass membrane protein. Endosome. Note=Interaction with SNX27 mediates recruitment to early endosomes, while interaction with SLC9A3R1 and EZR might target the protein to specialized subcellular regions, such as microvilli. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HTR4 Gene COMPARTMENTS Subcellular localization image for HTR4 gene
Compartment Confidence
endosome 5
plasma membrane 5
extracellular 1

Gene Ontology (GO) - Cellular Components for HTR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005768 endosome IEA --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IDA 16102731
genes like me logo Genes that share ontologies with HTR4: view

Pathways & Interactions for HTR4 Gene

genes like me logo Genes that share pathways with HTR4: view

Gene Ontology (GO) - Biological Process for HTR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007186 G-protein coupled receptor signaling pathway IEA,TAS 9351641
genes like me logo Genes that share ontologies with HTR4: view

No data available for SIGNOR curated interactions for HTR4 Gene

Drugs & Compounds for HTR4 Gene

Products:

  1. Drug

(87) Drugs for HTR4 Gene - From: DrugBank, ApexBio, DGIdb, FDA Approved Drugs, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cisapride Approved, Investigational, Withdrawn Pharma Partial agonist, Agonist, agonist, Target 5-HT4 agonist; stimulates intestinal ACh release 5
Ondansetron Approved Pharma Target, agonist 288
Metoclopramide Approved, Investigational Pharma Target, agonist Dopamine receptor antagonist 104
Cinitapride Approved Pharma Target, agonist 0
Zolmitriptan Approved, Investigational Pharma Full agonist, Agonist, agonist Potent 5-HT1B/1D/1F agonist 16

(11) Additional Compounds for HTR4 Gene - From: Novoseek, IUPHAR, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
5-HT
Full agonist, Agonist
alpha-methyl-5-HT
Full agonist, Agonist
2-[1-(4-Piperonyl)piperazinyl]benzothiazole
155106-73-3
RS 67333 hydrochloride
168986-60-5
RS 67506 hydrochloride
168986-61-6

(5) Tocris Compounds for HTR4 Gene

Compound Action Cas Number
2-[1-(4-Piperonyl)piperazinyl]benzothiazole 5-HT4 agonist. Also 5-HT3 antagonist 155106-73-3
Cisapride 5-HT4 agonist; stimulates intestinal ACh release 81098-60-4
RS 67333 hydrochloride 5-HT4 partial agonist 168986-60-5
RS 67506 hydrochloride 5-HT4 partial agonist 168986-61-6
Zacopride hydrochloride Highly potent 5-HT3 receptor antagonist. Also 5-HT4 agonist 101303-98-4

(39) ApexBio Compounds for HTR4 Gene

Compound Action Cas Number
Amitriptyline HCl Serotonin /norepinephrine receptor/5-HT4/5-HT2 inhibitor 549-18-8
Asenapine Inhibits adrenergic receptor/5-HT receptor 85650-56-2
Bilobalide Neuroprotective agent 33570-04-6
Blonanserin Atypical antipsychotic 132810-10-7
Clomipramine HCl SERT/NET dopamine transporter (DAT) blocker 17321-77-6
Dapoxetine HCl Selective serotonin reuptake inhibitor 129938-20-1
Desvenlafaxine 93413-62-8
Desvenlafaxine Succinate 386750-22-7
Duloxetine HCl 136434-34-9
Escitalopram Oxalate Serotonin(5-HT) reuptake (SSRI) inhibitor 219861-08-2
Fenspiride HCl 5053-08-7
Fluoxetine HCl Serotonin reuptake inhibitor,selective 56296-78-7
Fluvoxamine maleate Serotonin reuptake inhibitor,selective,antidepressant 61718-82-9
Ketanserin 74050-98-9
Lorcaserin HCl 846589-98-8
LY310762 192927-92-7
Milnacipran HCl 101152-94-7
Mosapride Citrate 5-HT receptor agonist 112885-42-4
Naratriptan 143388-64-1
Olanzapine 132539-06-1
Ondansetron 99614-02-5
Palonosetron HCl 135729-62-3
Pizotifen Malate 5189-11-7
Prucalopride Succinat 179474-85-2
Risperidone SR-2A inhibitor 106266-06-2
Rizatriptan Benzoate 145202-66-0
SB271046 209481-20-9
SEA0400 Specific inhibitor of Na+/Ca2+ exchange 223104-29-8
Sertraline HCl 79559-97-0
Tianeptine sodium 5-HT uptake facilitator,selective,antidepressant 30123-17-2
Trazodone HCl Antidepressant 25332-39-2
Tropisetron 105826-92-4
Urapidil HCl 64887-14-5
Venlafaxine Dual serotonin/noradrenalin re-uptake inhibitor 99300-78-4
Vortioxetine 5-HT receptors antagonist 508233-74-7
Vortioxetine (Lu AA21004) HBr 5-HT receptor modulator, antidepressant and anxiolytic 960203-27-4
VUF 10166 155584-74-0
Ziprasidone HCl Serotonin and dopamine receptor antagonist 122883-93-6
Zolmitriptan 139264-17-8
genes like me logo Genes that share compounds with HTR4: view

Transcripts for HTR4 Gene

Products:

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

mRNA/cDNA for HTR4 Gene

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

Unigene Clusters for HTR4 Gene

5-hydroxytryptamine (serotonin) receptor 4, G protein-coupled:
Representative Sequences:

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for HTR4 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b
SP1: - - - - -
SP2: - -
SP3: - - - - - - -
SP4: - - -
SP5: - - - -
SP6: - - - - -
SP7: - - - - - - - -
SP8: -
SP9:

Relevant External Links for HTR4 Gene

GeneLoc Exon Structure for
HTR4
ECgene alternative splicing isoforms for
HTR4

Expression for HTR4 Gene

Products:

  1. Primer

mRNA expression in normal human tissues for HTR4 Gene

mRNA expression in normal human tissues for HTR4 Gene
mRNA expression by BioGPS for HTR4 GenemRNA expression by GTEx for HTR4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HTR4 Gene

This gene is overexpressed in Brain - Nucleus accumbens (basal ganglia) (x8.1), Small Intestine - Terminal Ileum (x6.1), Brain - Caudate (basal ganglia) (x5.8), Colon - Transverse (x5.3), and Brain - Putamen (basal ganglia) (x4.0).

SOURCE GeneReport for Unigene cluster for HTR4 Gene Hs.483773

mRNA Expression by UniProt/SwissProt for HTR4 Gene

Q13639-5HT4R_HUMAN
Tissue specificity: Isoform 5-HT4(A) is expressed in ileum, brain, and atrium, but not in the ventricle.
genes like me logo Genes that share expression patterns with HTR4: view

Primer Products

No data available for Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for HTR4 Gene

Orthologs for HTR4 Gene

This gene was present in the common ancestor of animals.

Orthologs for HTR4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
 Mammalia HTR4 35
  • 93.73 (n)
  • 94.85 (a)
HTR4 36
  • 92 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia HTR4 35
  • 93.63 (n)
  • 96.63 (a)
HTR4 36
  • 94 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Htr4 35
  • 90.89 (n)
  • 93.3 (a)
Htr4 16
Htr4 36
  • 93 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia HTR4 35
  • 99.61 (n)
  • 99.77 (a)
HTR4 36
  • 100 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Htr4 35
  • 90.56 (n)
  • 92.73 (a)
oppossum
(Monodelphis domestica)
 Mammalia HTR4 36
  • 78 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia HTR4 36
  • 91 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves HTR4 35
  • 82.6 (n)
  • 88.46 (a)
HTR4 36
  • 89 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia HTR4 36
  • 85 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia LOC100493952 35
  • 74.52 (n)
  • 83.38 (a)
zebrafish
(Danio rerio)
 Actinopterygii LOC556843 35
  • 71.86 (n)
  • 75.32 (a)
HTR4 36
  • 73 (a)
 OneToOne
fruit fly
(Drosophila melanogaster)
 Insecta CG6919 37
  • 42 (a)
CG6989 37
  • 36 (a)
DopR 37
  • 35 (a)
oa2 35
  • 54.34 (n)
  • 47.54 (a)
oa2 36
  • 28 (a)
 ManyToMany
Octbeta2R 36
  • 26 (a)
 ManyToMany
Species with no ortholog for HTR4:
  • 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for HTR4 Gene

ENSEMBL:
Gene Tree for HTR4 (if available)
TreeFam:
Gene Tree for HTR4 (if available)

Paralogs for HTR4 Gene

Paralogs for HTR4 Gene

(29) SIMAP similar genes for HTR4 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with HTR4: view

Variants for HTR4 Gene

Sequence variations from dbSNP and Humsavar for HTR4 Gene

SNP ID Clin Chr 05 pos Sequence Context AA Info Type
rs34826744 - 148,483,255(-) TCAGT(A/G)TCACC intron-variant, nc-transcript-variant, reference, missense
VAR_067412 -
rs723180 -- 148,516,971(-) ATTTC(C/T)TTTGG intron-variant
rs723181 -- 148,516,761(-) CTTTA(A/G)TTAAG intron-variant
rs867279 -- 148,586,456(+) AGTCC(A/G)TTTTC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for HTR4 Gene

Variant ID Type Subtype PubMed ID
nsv830516 CNV Loss 17160897
nsv523792 CNV Loss 19592680
esv270273 CNV Insertion 20981092
nsv328933 CNV Loss 16902084

Variation tolerance for HTR4 Gene

Residual Variation Intolerance Score: 28.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.83; 47.89% of all genes are more intolerant (likely to be disease-causing)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Relevant External Links for HTR4 Gene

Disorders for HTR4 Gene

MalaCards: The human disease database

(12) MalaCards diseases for HTR4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
constipation
irritable bowel syndrome
  • ibd
gastrointestinal system disease
  • alimentary system disease
dyspepsia
  • dyspepsia, indigestion nos
stomach disease
  • gastric disease
- elite association - COSMIC cancer census association via MalaCards
Search HTR4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for HTR4

Genetic Association Database (GAD)
HTR4
Human Genome Epidemiology (HuGE) Navigator
HTR4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HTR4
genes like me logo Genes that share disorders with HTR4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HTR4 Gene

Publications for HTR4 Gene

  1. Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia. (PMID: 12898568) Suzuki T. … Ozaki N. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2003) 3 23 48 67
  2. 5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle. (PMID: 11218067) Bach T. … Levy F.O. (Naunyn Schmiedebergs Arch. Pharmacol. 2001) 3 25 26
  3. Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5-HT4) receptors. (PMID: 18948374) Guillemot J. … Lefebvre H. (Endocr. Relat. Cancer 2009) 25 26
  4. Heterologous expression and purification of the serotonin type 4 receptor from transgenic mouse retina. (PMID: 19053287) Salom D. … Salon J.A. (Biochemistry 2008) 3 23
  5. 5-hydroxytryptamine 4 receptor activation of the extracellular signal-regulated kinase pathway depends on Src activation but not on G protein or beta-arrestin signaling. (PMID: 17377064) Barthet G. … Dumuis A. (Mol. Biol. Cell 2007) 3 23

Products for HTR4 Gene

  • Addgene plasmids for HTR4

Sources for HTR4 Gene

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