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    HTR4 5-hydroxytryptamine receptor 4 [ Homo sapiens (human) ]

    Gene ID: 3360, updated on 14-Nov-2024

    Summary

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    Official Symbol
    HTR4provided by HGNC
    Official Full Name
    5-hydroxytryptamine receptor 4provided by HGNC
    Primary source
    HGNC:HGNC:5299
    See related
    Ensembl:ENSG00000164270 MIM:602164; AllianceGenome:HGNC:5299
    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
    5-HT4; 5-HT4R
    Summary
    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]
    Expression
    Biased expression in small intestine (RPKM 2.1), duodenum (RPKM 1.1) and 5 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HTR4 in Genome Data Viewer
    Location:
    5q32
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (148451032..148654527, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (148985559..149189026, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (147830595..148034090, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene FBXO38 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23363 Neighboring gene serine peptidase inhibitor Kazal type 9 Neighboring gene MPRA-validated peak5528 silencer Neighboring gene PRELI domain containing 3B pseudogene 9 Neighboring gene F-box protein 38 Neighboring gene uncharacterized LOC107986462 Neighboring gene NANOG hESC enhancer GRCh37_chr5:148099086-148099657 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23364 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23365 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23366 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16490 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23367 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23368 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23369 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:148206489-148207074 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16492 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16491 Neighboring gene MPRA-validated peak5531 silencer Neighboring gene adrenoceptor beta 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:148289701-148290900 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_82030 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr5:148335980-148336552 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:148349629-148350210 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:148358305-148358824 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:148363540-148364739 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_82036 Neighboring gene SH3 domain and tetratricopeptide repeats 2 Neighboring gene RNA, U6 small nuclear 732, pseudogene

    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 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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Concurrent anxiety in patients with major depression and cerebral serotonin 4 receptor binding. A NeuroPharm-1 study.
      Title: Concurrent anxiety in patients with major depression and cerebral serotonin 4 receptor binding. A NeuroPharm-1 study.
    2. The GG genotype of the serotonin 4 receptor genetic polymorphism, rs1345697, is associated with lower remission rates after antidepressant treatment: Findings from the METADAP cohort.
      Title: The GG genotype of the serotonin 4 receptor genetic polymorphism, rs1345697, is associated with lower remission rates after antidepressant treatment: Findings from the METADAP cohort.
    3. Hypomethylation of the HTR4 promoter is a potential biomarker for predicting the risk of male Autism Spectrum Disorder in Chinese people.
      Title: Association of human serotonin receptor 4 promoter methylation with autism spectrum disorder.
    4. The down-regulation effects of IFN-alpha on p11, 5-HT1b and 5-HT4 were associated with the lysosome and ubiquitin-proteasome-mediated pathways. p11 was identified as a potent regulator to modulate the ubiquitination of 5-HT1b and 5-HT4. Therefore, it could be potential target therapies in IFN-ainduced depression
      Title: Down-regulation effects of IFN-α on p11, 5-htr1b and 5-HTR4 protein levels were affected by NH(4)CL or MG132 treatment in SH-sy5y cells.
    5. In human large intestinal circular muscle, the intracellular pathway of 5-HT4 receptors facilitating cholinergic neurotransmission to large intestinal circular smooth muscle is controlled by phosphodiesterase 4.
      Title: Synergy between 5-HT(4) receptor stimulation and phosphodiesterase 4 inhibition in facilitating acetylcholine release in human large intestinal circular muscle.
    6. this study shows that HTR$ gene expression regulation is affected by mir-16 and mir-103 single nucleotide polymorphisms
      Title: miR-16 and miR-103 impact 5-HT(4) receptor signalling and correlate with symptom profile in irritable bowel syndrome.
    7. found that testosterone, but not estradiol, correlated negatively with global 5-HT4R levels suggesting that men with high levels of testosterone have higher cerebral serotonergic tonus.
      Title: Testosterone levels in healthy men correlate negatively with serotonin 4 receptor binding.
    8. l-Lysine significantly reduced the surge of plasma aldosterone induced by metoclopramide indicating that l-Lysine is able to efficiently antagonize the adrenal 5-HT4 receptors in vivo.
      Title: l-Lysine Acts as a Serotonin Type 4 Receptor Antagonist to Counteract In Vitro and In Vivo the Stimulatory Effect of Serotonergic Agents on Aldosterone Secretion in Man.
    9. Acute administration of 5-hydroxytryptamine4 (5-HT4) receptor agonist, mosapride or esophageal infusion of the transient receptor potential vanilloid receptor-1 (TRPV1) agonist capsaicin promotes secondary peristalsis.Esophageal infusion with capsaicin-containing red pepper sauce suspension does create greater mechanosensitivity as measured by secondary peristalsis than 5-HT4 receptor agonist mosapride
      Title: Differences in the Control of Secondary Peristalsis in the Human Esophagus: Influence of the 5-HT4 Receptor versus the TRPV1 Receptor.
    10. Findings replicate our previous observation of a negative association between 5-HT 4R binding and memory performance in an independent cohort and provide novel evidence linking 5-HT 4R binding, as a biomarker for synaptic 5-HT levels, to the mnestic processing of positive and neutral word stimuli in healthy humans
      Title: Brain serotonin 4 receptor binding is inversely associated with verbal memory recall.
    Submit: New GeneRIF Correction See all GeneRIFs (63)

    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
    Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction.
    EBI GWAS Catalog
    Genome-wide association study identifies five loci associated with lung function.
    EBI GWAS Catalog
    Genome-wide association study of periodontal pathogen colonization.
    EBI GWAS Catalog
    Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.
    EBI GWAS Catalog
    Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.
    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)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of 5-hydroxytryptamine (serotonin) receptor 4, G protein-coupled (HTR4) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Potential readthrough

    Included gene: SH3TC2

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables G protein-coupled serotonin receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables G protein-coupled serotonin receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables neurotransmitter receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serotonin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serotonin receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    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-activating G protein-coupled receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in adenylate cyclase-activating serotonin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in adenylate cyclase-inhibiting serotonin receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in chemical synaptic transmission IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in large intestinal transit IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in maintenance of gastrointestinal epithelium IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mucus secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of appetite IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of postsynapse assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in dendrite IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endosome membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IC
    Inferred by Curator
    more info
    		 PubMed 
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in postsynapse IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    5-hydroxytryptamine receptor 4
    Names
    5-hydroxytryptamine (serotonin) receptor 4, G protein-coupled
    cardiac 5-HT4 receptor

    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.

    Genomic

    1. NG_029052.1 RefSeqGene

      Range
      4650..177630
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000870.7 → NP_000861.1  5-hydroxytryptamine receptor 4 isoform b

      See identical proteins and their annotated locations for NP_000861.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (b) encodes the longest isoform (b).
      Source sequence(s)
      AC008627, AC091971, AJ131724, DR000612
      Consensus CDS
      CCDS4291.1
      UniProtKB/Swiss-Prot
      C4WYH4, Q13639, Q546Q1, Q684M0, Q712M9, Q96KH9, Q96KI0, Q9H199, Q9NY73, Q9UBM6, Q9UBT4, Q9UE22, Q9UE23, Q9UQR6
      UniProtKB/TrEMBL
      A0A2D3FAF9, Q8IXH9
      Related
      ENSP00000367120.4, ENST00000377888.8
      Conserved Domains (1) summary
      cd15056
      Location:20 → 323
      7tmA_5-HT4; serotonin receptor subtype 4, member of the class A family of seven-transmembrane G protein-coupled receptors

    2. NM_001040169.2 → NP_001035259.1  5-hydroxytryptamine receptor 4 isoform a

      See identical proteins and their annotated locations for NP_001035259.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a) differs in the 5' UTR, 3' coding region and 3' UTR, compared to variant b. The resulting isoform (a) has a distinct C-terminus and is shorter than isoform b.
      Source sequence(s)
      AC114939, AJ131724, AJ278979, Y08756
      Consensus CDS
      CCDS34270.1
      UniProtKB/TrEMBL
      E5RK45
      Related
      ENSP00000428320.1, ENST00000521530.6
      Conserved Domains (1) summary
      pfam00001
      Location:36 → 312
      7tm_1; 7 transmembrane receptor (rhodopsin family)

    3. NM_001040172.2 → NP_001035262.2  5-hydroxytryptamine receptor 4 isoform d

      See identical proteins and their annotated locations for NP_001035262.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (d) differs in the 5' UTR and uses an alternate 3' terminal exon compared to variant b. The encoded isoform (d) has a distinct C-terminus and is shorter than isoform b.
      Source sequence(s)
      AC091971, AJ131724, Y12507
      Consensus CDS
      CCDS34273.2
      UniProtKB/TrEMBL
      E5RK45
      Related
      ENSP00000435904.1, ENST00000517929.5
      Conserved Domains (1) summary
      pfam00001
      Location:36 → 312
      7tm_1; 7 transmembrane receptor (rhodopsin family)

    4. NM_001040173.2 → NP_001035263.1  5-hydroxytryptamine receptor 4 isoform i

      See identical proteins and their annotated locations for NP_001035263.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (i) differs in the 5' UTR and includes an alternate in-frame exon, compared to variant b. This results in a longer protein (isoform i), compared to isoform b.
      Source sequence(s)
      AC091971, AJ131724, AJ131726
      Consensus CDS
      CCDS34272.1
      UniProtKB/TrEMBL
      Q8IXH9
      Related
      ENSP00000353915.3, ENST00000360693.7
      Conserved Domains (1) summary
      pfam00001
      Location:36 → 312
      7tm_1; 7 transmembrane receptor (rhodopsin family)

    5. NM_001286410.1 → NP_001273339.1  5-hydroxytryptamine receptor 4 isoform c

      See identical proteins and their annotated locations for NP_001273339.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (c) has a shorter 5' UTR and uses an alternate exon in the 3' UTR and coding region. The encoded isoform (c) is shorter and has a distinct C-terminus compared to isoform b.
      Source sequence(s)
      AC008627, AM712912, Y12506
      Consensus CDS
      CCDS75353.1
      UniProtKB/TrEMBL
      E5RK45
      Related
      ENSP00000427913.1, ENST00000520514.5
      Conserved Domains (2) summary
      pfam00001
      Location:36 → 312
      7tm_1; 7 transmembrane receptor (rhodopsin family)
      cl21561
      Location:26 → 215
      7tm_4; Olfactory receptor

    6. NM_199453.3 → NP_955525.1  5-hydroxytryptamine receptor 4 isoform g

      See identical proteins and their annotated locations for NP_955525.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (g), also known as E or G1, differs in the 5' UTR, 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (isoform g) has a distinct C-terminus and is shorter than isoform b.
      Source sequence(s)
      AC114939, AJ011371, AJ131724, AJ278981, Y08756
      Consensus CDS
      CCDS34271.1
      UniProtKB/TrEMBL
      E5RK45
      Related
      ENSP00000430979.1, ENST00000521735.5
      Conserved Domains (1) summary
      pfam00001
      Location:36 → 312
      7tm_1; 7 transmembrane receptor (rhodopsin family)

    RNA

    1. NR_104445.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (j) uses an alternate exon at the 3' end compared to variant b. This variant (j) is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC008627, AC091971, AK308471

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      148451032..148654527 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      148985559..149189026 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001040174.1: Suppressed sequence

      Description
      NM_001040174.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13639.2 GenPept UniProtKB/Swiss-Prot:Q13639

    Gene LinkOut

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

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