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

Summary

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

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_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed
Genome-wide association study identifies five loci associated with lung function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of periodontal pathogen colonization. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

HTR4 (e-PCR)
- UniSTS:504885

RH120547 (e-PCR)
- UniSTS:133712

Htr4 (e-PCR), detects polymorphism
- UniSTS:495967

NoName (e-PCR)
- UniSTS:481913

D5S1425 (e-PCR)
- UniSTS:68552

D5S1748 (e-PCR)
- UniSTS:61139

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

NG_029052.1 RefSeqGene

Range

4650..177630

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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)
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)
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)
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
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

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

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

148451032..148654527 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060929.1 Alternate T2T-CHM13v2.0

Range

148985559..149189026 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.