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HTR4 Gene

protein-coding GIFtS: 70
GCID: GC05M147810

5-Hydroxytryptamine (Serotonin) Receptor 4, G Protein-Coupled

(Previous name: 5-hydroxytryptamine (serotonin) receptor 4)

See HTR4-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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This gene clusters with an RNA gene
Subcategory (RNA class): lncRNA

Quality score for the ORGUL clustered with this gene is 3

Aliases
5-Hydroxytryptamine (Serotonin) Receptor 4, G Protein-Coupled¹ ²		5-Hydroxytryptamine Receptor 4²
5-HT4² ³		Cardiac 5-HT4 Receptor²
5-Hydroxytryptamine (Serotonin) Receptor 4¹		5-HT-4³
5-HT4R²		Serotonin Receptor 4³

External Ids:	HGNC: 5299¹	Entrez Gene: 3360²	Ensembl: ENSG00000164270⁷	OMIM: 602164⁵	UniProtKB: Q13639³

ORGUL members:

Export aliases for HTR4 gene to outside databases

Previous GC identifers: GC05M147904 GC05M148425 GC05M147859 GC05M142977

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 (serotonin) receptor 4, G protein-coupled) is a protein-coding gene. Diseases associated with HTR4 include functional colonic disease, and hereditary diffuse leukoencephalopathy with spheroids. GO annotations related to this gene include serotonin receptor activity. An important paralog of this gene is TAAR6.

UniProtKB/Swiss-Prot: 5HT4R_HUMAN, Q13639

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

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.

The human 5-HT4 receptor gene has been localized to chromosome 5 (5q31-33).

Gene Wiki entry for HTR4 (5-HT4 receptor) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000005.9 NC_018916.2 NT_029289.12

Regulatory elements:

Regulatory transcription factor binding sites in the HTR4 gene promoter:
Pax-5 Egr-1 CUTL1 HNF-3beta RORalpha2 Roaz C/EBPalpha AREB6 MEF-2A S8
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: HTR4 promoter sequence

Search Chromatin IP Primers for HTR4

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HTR4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5q31-q33 Ensembl cytogenetic band: 5q32 HGNC cytogenetic band: 5q31-q33

HTR4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HTR4 gene location

GeneLoc information about chromosome 5 GeneLoc Exon Structure

GeneLoc location for GC05M147810: view genomic region (about GC identifiers)

Start:	147,830,595 bp from pter	End:	148,056,798 bp from pter
Size:	226,204 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: 5HT4R_HUMAN, Q13639 (See protein sequence)

Recommended Name: 5-hydroxytryptamine receptor 4

Size: 388 amino acids; 43761 Da

Subunit: 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)

Secondary accessions: C4WYH4 Q546Q1 Q684M0 Q712M9 Q96KH9 Q96KI0 Q9H199 Q9NY73 Q9UBM6 Q9UBT4

Q9UE22 Q9UE23 Q9UQR6

Alternative splicing: 9 isoforms: Q13639-1 Q13639-2 Q13639-3 Q13639-4 Q13639-5 Q13639-6 Q13639-7 Q13639-8

Q13639-9 (Expressed in all cardiovascular tissues analyzed)

Explore the universe of human proteins at neXtProt for HTR4: NX_Q13639

Explore proteomics data for HTR4 at MOPED

Post-translational modifications:

Glycosylation² at Asn7

See HTR4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (6 alternative transcripts):

NP_000861.1 NP_001035259.1 NP_001035262.2 NP_001035263.1 NP_001273339.1 NP_955525.1

ENSEMBL proteins:

ENSP00000428320 ENSP00000430874 ENSP00000430979 ENSP00000435904 ENSP00000427913

ENSP00000367120 ENSP00000353915 ENSP00000430451 ENSP00000429634 ENSP00000346156

ENSP00000314906 ENSP00000355037

Reactome Protein details: Q13639

HTR4 Human Recombinant Protein Products:

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	Cloud-Clone Corp. Proteins for HTR4
	Search eBioscience for Proteins for HTR4
	antibodies-online proteins for HTR4 (4 products)
	antibodies-online peptides for HTR4

HTR4 Antibody Products:

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	antibodies-online antibodies for HTR4 (52 products)

HTR4 Assay Products:

	Browse Kits and Assays available from EMD Millipore
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	GenScript Custom Assay Services for HTR4
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for HTR4 Cloud-Clone Corp. CLIAs for HTR4
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	antibodies-online kits for HTR4 (11 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

HTR: 5-HT (serotonin) receptors

HTRGP: GPCR / Class A : 5-HT (serotonin) receptors, GPCR only

IUPHAR Guide to PHARMACOLOGY protein family classification: 5-HT₄ receptor

5-Hydroxytryptamine receptors

3 InterPro protein domains:

IPR017452 GPCR_Rhodpsn_7TM

IPR001520 5HT4_rcpt

IPR000276 GPCR_Rhodpsn

Graphical View of Domain Structure for InterPro Entry Q13639

ProtoNet protein and cluster: Q13639

2 Blocks protein domains:

IPB001520 5-hydroxytryptamine 4 receptor signature

IPB002233 Adrenergic receptor signature

UniProtKB/Swiss-Prot: 5HT4R_HUMAN, Q13639

Similarity: Belongs to the G-protein coupled receptor 1 family

Find genes that share domains with HTR4 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: 5HT4R_HUMAN, Q13639

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

Genatlas biochemistry entry for HTR4:

5-hydroxytryptamine (serotonin) receptor,subtype 4A,and three splice variants 4B,4C,4D,G protein coupled receptor

superfamily,activating adenylate cyclase

Gene Ontology (GO): 3 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004930	G-protein coupled receptor activity	--	--
GO:0004993	serotonin receptor activity	IDA	16102731
GO:0005515	protein binding	--	--

Find genes that share ontologies with HTR4 About GenesLikeMe

Phenotypes:
6 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Htr4):

adipose tissue	behavior/neurological	growth/size/body	homeostasis/metabolism	mortality/aging
nervous system

Find genes that share phenotypes with HTR4 About GenesLikeMe

Animal Models:
MGI mouse knock-out Htr4^tm1Comp for HTR4

genOway: Develop your customized and physiologically relevant rodent model for HTR4

miRNA Products:		Block miRNA regulation of human, mouse, rat HTR4 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate HTR4 (see all 43):
		hsa-miR-548j hsa-let-7d hsa-miR-631 hsa-miR-15a hsa-miR-503 hsa-let-7g hsa-miR-424 hsa-let-7a

		SwitchGear 3'UTR luciferase reporter plasmids (see all 2): HTR4 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for HTR4
		Predesigned siRNA for gene silencing in human, mouse, rat HTR4

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for HTR4

Clone Products:		OriGene clones in human, mouse for HTR4 (see all 36) OriGene ORF clones in mouse, rat for HTR4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 5): HTR4 (NM_199453)
		Sino Biological Human cDNA Clone for HTR4
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for HTR4
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat HTR4
		Addgene plasmids for HTR4

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for HTR4
		Browse ESI BIO Cell Lines and PureStem Progenitors for HTR4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HTR4

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

5HT4R_HUMAN, Q13639: 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 (By similarity)

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
endosome	5
plasma membrane	5

About this image

Gene Ontology (GO): Selected cellular component terms (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	IDA	15925089
GO:0005768	endosome	IEA	--
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral component of plasma membrane	IEA	--
GO:0016020	membrane	IDA	16102731

Find genes that share ontologies with HTR4 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for HTR4 About (see all 10)

See pathways by source

Powered
by

SuperPath

Contained pathways About

Peptide ligand-binding receptors

	Class A/1 (Rhodopsin-like receptors)	0.71			GPCRs, Class A Rhodopsin-like	0.43
	GPCR ligand binding	0.71			Neuroactive ligand-receptor interaction	0.36

Monoamine GPCRs

	Monoamine GPCRs	0.79			Serotonin receptors	0.00
	Amine ligand-binding receptors	0.79

Signaling by GPCR

	Signaling by GPCR	0.90			Signal Transduction	0.58
	GPCR downstream signaling	0.90

Development Ligand-independent activation of ESR1 and ESR2

Development Ligand-independent activation of ESR1 and ESR2

0.35

Transcription CREB pathway

0.34

CREB Pathway

Intracellular Calcium Signaling

0.50

Find genes that share SuperPaths with HTR4 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for HTR4

Intracellular Calcium Signaling

2 GeneGo (Thomson Reuters) Pathways for HTR4

	Development Ligand-independent activation of ESR1 and ESR2
	Transcription CREB pathway

3 BioSystems Pathways for HTR4

	Serotonin Receptor 4/6/7 and NR3C Signaling
	GPCRs, Class A Rhodopsin-like
	Monoamine GPCRs

2 Reactome Pathways for HTR4

	Serotonin receptors
	G alpha (s) signalling events

1 PharmGKB Pathway for HTR4

Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics

3 Kegg Pathways (Kegg details for HTR4):

	Calcium signaling pathway
	Neuroactive ligand-receptor interaction
	Serotonergic synapse

Pathway & Disease-focused RT² Profiler PCR Arrays including HTR4:

Neurotransmitter Receptors in human mouse rat

G Protein Coupled Receptors 384HT in human mouse rat

Interactions:

GeneGlobe Interaction Network for HTR4

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for HTR4 (Q13639^{2, 3} ENSP00000353915⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 67)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
ADRB2	P07550²^,³, ENSP00000305372⁴	MINT-60083 I2D: score=1 STRING: ENSP00000305372
HTR4	Q13639²	MINT-60079 MINT-60081 MINT-60077 MINT-60082 MINT-60078 MINT-60080
ADCY1	ENSP00000297323⁴	STRING: ENSP00000297323
ADCY2	ENSP00000342952⁴	STRING: ENSP00000342952
ADCY8	ENSP00000286355⁴	STRING: ENSP00000286355

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Gene Ontology (GO): Selected biological process terms (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0007186	G-protein coupled receptor signaling pathway	TAS	9351641
GO:0007187	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	TAS	9603189
GO:0007210	serotonin receptor signaling pathway	TAS	9603189
GO:0007268	synaptic transmission	IEA	--
GO:0008284	positive regulation of cell proliferation	IMP	15925089

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Compounds for HTR4 available from Tocris Bioscience About this table

Compound	Action	CAS #
RS 39604 hydrochloride	5-HT4 antagonist	[167710-87-4]
RS 67333 hydrochloride	5-HT4 partial agonist	[168986-60-5]
BIMU 8	Potent 5-HT4 receptor full agonist	[134296-40-5]
GR 125487 sulfamate	Potent, selective 5-HT4 antagonist. Active in vivo	[144625-67-2]
GR 113808	Potent, selective 5-HT4 antagonist	[144625-51-4]

1 HMDB Compound for HTR4 About this table

Compound	Synonyms	CAS #	PubMed Ids
Serotonin	3-(2-Aminoethyl)-1H-indol-5-ol (see all 14)	50-67-9	--

5 DrugBank Compounds for HTR4 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Cisapride	--	81098-60-4	target	agonist	11034583 10027842 10328995 11752352 11218067 10556228
Tegaserod	SDZ HTF 919 (see all 2)	189188-57-6	target	antagonist partial agonist	15645012 11876686 12150698 11207504 11752352 15466450
Cinitapride	--	66564-14-5	target	agonist	9562338 9211565
Metoclopramide	Metaclopramide (see all 9)	364-62-5	target	agonist	18948374
Ondansetron	--	99614-02-5	target	agonist	2164935

Selected IUPHAR Ligands for HTR4 (5-HT₄ receptor) (see all 28) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
RS 100235	Antagonist	Antagonist	8.7 - 12.2	9351641 15351779
GR 125487	Antagonist	Antagonist	9.8 - 10.7	9351641 9349523
piboserod	Antagonist	Antagonist	8.8 - 10.4	9351641 15466450 11504648
SB 204070	Antagonist	Antagonist	9.8 - 10.4	10646498 11030734 9349523 10683202
SB 207710	Antagonist	Antagonist	10.1 - 10.3	11218067
GR 113808	Antagonist	Antagonist	9.3 - 10.3	9349523 11218067 15351779 9351641 10646498 11030734 9603189
ML 10375	Antagonist	Antagonist	8.8 - 10	15466450 10683202 9603189 10821780 11030734
[³H]GR 113808	Antagonist	Antagonist	10.3 - 9.7	10646498 9349523 11218067 10821780
RS 116 2617	Antagonist	Inverse agonist	9.6	11976337
SL65.0155	Agonist	Partial agonist	9.2	12130738

Selected Novoseek inferred chemical compound relationships for HTR4 gene (see all 28) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
tegaserod	92.5	27	16817836 (3), 12358251 (2), 11743242 (1), 12946544 (1) (see all 20)
gr 113808	86.7	4	19615378 (1), 15007537 (1), 7965722 (1), 15950987 (1)
renzapride	86.4	5	1600046 (1), 1330164 (1), 18922103 (1), 16696817 (1)
cisapride	86	10	9506010 (2), 7949460 (1), 10780971 (1), 14501621 (1) (see all 8)
mosapride	83.4	8	16153398 (2), 16173472 (2), 14501621 (1), 19889470 (1) (see all 6)
5-hydroxytryptamine	83.2	52	9862758 (3), 10543288 (2), 8959736 (2), 12358251 (2) (see all 27)
tropisetron	81.6	7	10543288 (1), 9826103 (1), 1600046 (1), 1330164 (1) (see all 5)
5-methoxytryptamine	80.8	4	10543288 (1), 7599849 (1), 12580024 (1), 16702620 (1)
methiothepin	79.4	3	7599849 (1), 1330164 (1), 16702620 (1)
2-methyl-5-ht	72.5	1	10543288 (1)

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for HTR4 gene (7 alternative transcripts):

NM_000870.6 NM_001040169.2 NM_001040172.2 NM_001040173.2 NM_001286410.1 NM_199453.3 NM_001040174.1

Unigene Cluster for HTR4:

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

Hs.483773 [show with all ESTs]

Unigene Representative Sequence: AJ131724

14 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000521530 ENST00000522588 ENST00000521735 ENST00000517929(uc021yfi.1)

ENST00000520514(uc011dby.1) ENST00000377888 ENST00000360693(uc021yfj.1)

ENST00000524063 ENST00000521124(uc021yfk.1) ENST00000519495 ENST00000520086(uc003lpq.1)

ENST00000354217(uc021yfh.1) ENST00000314512(uc021yfg.1 uc010jgu.1)

ENST00000362016(uc003lpn.3 uc010jgv.3)

miRNA Products:		Block miRNA regulation of human, mouse, rat HTR4 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate HTR4 (see all 43):
		hsa-miR-548j hsa-let-7d hsa-miR-631 hsa-miR-15a hsa-miR-503 hsa-let-7g hsa-miR-424 hsa-let-7a

		SwitchGear 3'UTR luciferase reporter plasmids (see all 2): HTR4 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for HTR4
		Predesigned siRNA for gene silencing in human, mouse, rat HTR4

Clone Products:		OriGene clones in human, mouse for HTR4 (see all 36) OriGene ORF clones in mouse, rat for HTR4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 5): HTR4 (NM_199453)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for HTR4
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		Addgene plasmids for HTR4

Primer Products:		OriGene qPCR primer pairs and template standards for HTR4 OriGene qSTAR qPCR primer pairs in human, mouse for HTR4
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat HTR4
		QuantiTect SYBR Green Assays in human, mouse, rat HTR4
		QuantiFast Probe-based Assays in human, mouse, rat HTR4

Additional mRNA sequence:

AJ011371.1 AJ131724.1 AJ131725.1 AJ131726.1 AJ278979.1 AJ278980.1 AJ278981.1 AJ278982.1

AJ519673.1 AJ633645.1 AK095223.1 AK308471.1 AM712912.1 BC074755.2 BC095497.1 Y08756.1

Y09586.1 Y10437.1 Y12505.1 Y12506.1 Y12507.1 Y13584.1 Z48150.1

10 DOTS entries:

DT.40234835 DT.91661182 DT.108819 DT.99937173 DT.102830595 DT.95149585 DT.101972406 DT.91661178

DT.95332349 DT.120832090

Selected AceView cDNA sequences (see all 113):

AJ278982 Y12505 AK127050 BX283793 AJ278980 NM_199453 BE302852 AK124854

AJ011371 Z48150 AI033298 CB141690 AJ131725 BI054444 NM_024577 AK095223

CF147797 BC074755 AJ519673 CR595950 BQ213149 Y10437 AJ131726 BX386178

GeneLoc Exon Structure

Selected Alternative Splicing Database (ASD) splice patterns (SP) for HTR4 (see all 9) About this scheme

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:											-										-		-		-

ECgene alternative splicing isoforms for HTR4

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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HTR4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: GCCTGCCTGC

About this image

HTR4 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 4) fully expand


Brain (Nervous System) fully expand to see all 3 entries
Cerebellum

Ovary (Reproductive System)
Oviduct

Testis (Reproductive System)
Leydig Cells Testis Interstitium

Liver (Hepatobiliary System)
Hepatocytes Liver Lobule

HTR4 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

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HTR4 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.483773

UniProtKB/Swiss-Prot: 5HT4R_HUMAN, Q13639

Tissue specificity: Isoform 5-HT4(A) is expressed in ileum, brain, and atrium, but not in the ventricle

Pathway & Disease-focused RT² Profiler PCR Arrays including HTR4:

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for HTR4 gene from Selected species (see all 12) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Htr4^{1 , 5}	5 hydroxytryptamine (serotonin) receptor 4^{1, 5}	90.89(n)¹ 93.3(a)¹		18 (35.10 cM)⁵ 15562¹ NM_008313.4¹ NP_032339.2¹ 62324204⁵
chicken (Gallus gallus)	Aves	HTR4¹	5-hydroxytryptamine (serotonin) receptor 4, G protein-coupled	82.6(n) 88.46(a)		416150 XM_414481.4 XP_414481.4
lizard (Anolis carolinensis)	Reptilia	HTR4⁶	5-hydroxytryptamine (serotonin) receptor 4, G prot...	85(a)	1 ↔ 1	2(121764217-122004739)
tropical clawed frog (Xenopus tropicalis)	Amphibia	LOC100493952¹	5-hydroxytryptamine receptor 4-like	74.52(n) 83.38(a)		100493952 XM_002939806.2 XP_002939852.1
zebrafish (Danio rerio)	Actinopterygii	LOC556843¹	5-hydroxytryptamine receptor 4-like	71.86(n) 75.32(a)		556843 XM_679765.5 XP_684857.5
fruit fly (Drosophila melanogaster)	Insecta	CG6919³ oa2¹	G-protein coupled receptor protein signaling pathway more³ octopamine receptor 2¹	42(a) (best of 3)³ 54.34(n)¹ 47.54(a)¹		94B2³ 42652¹ NM_001275914.1¹ NP_001262843.1¹

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

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for HTR4 gene

TAAR6² HTR6² TAAR2² ADRB1² TAAR9² TAAR8² HRH2² DRD1²

TAAR1² ADRB2² ADRB3² DRD5² TAAR5²

Selected SIMAP similar genes for HTR4 using alignment to 3 protein entries: 5HT4R_HUMAN (see all proteins) (see all similar genes):

HTR4B ADORA2A HTR2B DRD2 GHSR HRH2

TAAR1 ADRB2 TAAR2 TAAR3 TAAR5 DRD5P1

TAAR9 hA2aR TAAR6 DRD1 DRD5 GPR85

Find genes that share paralogs with HTR4 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 5 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs199889746^1,2	C	untested¹	148165185(+)	`ACTTCC/TTCTTT`	10	K R	mis¹		0	--	--	--	--
rs60708069^1,2		--	142984608(+)	`TTTAAG/TATCTA`	2	--	int¹		0	--	--	--	--
rs3957780^1,2	C	--	142984644(+)	`attttA/Catatc`	2	--	int¹		0	--	--	--	--
rs113028635^1,2	F	--	142984646(+)	`TTTAAG/TATCTA`	2	--	int¹		1		CSA	2
rs137977633^1,2	C	--	143004824(+)	`AGAAA-/GAGGAC`	3	--	int¹		0	--	--	--	--
rs71583977^1,2	C	--	143010486(+)	`TTATT-/ATTTAT TT/TATTTGAGCC`	5	--	int¹		1		NA	2
rs113992728^1,2	C	--	143034084(+)	`TCTTC-/AAAAAA`	5	--	int¹		1		CSA	2
rs139437160^1,2	C	--	143114566(+)	`TTAAT-/C/TC TTTTT`	5	--	int¹		0	--	--	--	--
rs150006977^1,2	C	--	143116439(+)	`TCAAG-/TGATTC`	5	--	int¹		0	--	--	--	--
rs5872086^1,2	C	--	143135608(+)	`AAGGG-/Tttttt`	5	--	int¹ trp³		0	--	--	--	--

HapMap Linkage Disequilibrium report for HTR4 (147830595 - 148056798 bp)

Structural Variations
Database of Genomic Variants (DGV) 4 variations for HTR4: About this table

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

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing HTR4

DNA2.0 Custom Variant and Variant Library Synthesis for HTR4

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 602164 OMIM disorders: --

3 diseases for HTR4:
About MalaCards

functional colonic disease hereditary diffuse leukoencephalopathy with spheroids colonic disease

4 inferred disease relationships from the University of Copenhagen DISEASES database for HTR4:

Constipation Gastroparesis Functional colonic disease Irritable bowel syndrome

Find genes that share disorders with HTR4 About GenesLikeMe

8 Novoseek inferred disease relationships for HTR4 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
functional dyspepsia	61.9	2	17439064 (1), 16827813 (1)
gastrointestinal diseases	46.7	2	18415081 (1), 20197377 (1)
motility disorder	34.2	1	12358251 (1)
reflux	30.7	3	14501621 (1), 11929392 (1)
schizophrenia	7.87	5	12898568 (3), 12399948 (1), 20197377 (1)
atrial fibrillation	5.94	1	11215536 (1)
tumors	0.624	2	12530699 (1), 15326569 (1)
genetic susceptibility	0	2	12898568 (1), 17572793 (1)

Genetic Association Database (GAD): HTR4
Human Genome Epidemiology (HuGE) Navigator: HTR4 (17 documents)

Export disorders for HTR4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for HTR4 gene, integrated from 10 sources (see all 245):
(articles sorted by number of sources associating them with HTR4)

Utopia: connect your pdf to the dynamic
world of online information

Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia. (PubMed id 12898568)^{1, 4, 9} Suzuki T....Ozaki N. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2003)
Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees. (PubMed id 12399948)^{1, 4, 9} Ohtsuki T....Arinami T. (Mol. Psychiatry 2002)
Cloning, expression, and pharmacology of four human 5- hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus. (PubMed id 9603189)^{1, 2, 9} Blondel O.... Fischmeister R. (J. Neurochem. 1998)
Expression of serotonin receptor mRNAs in blood vessels. (PubMed id 7656980)^{1, 2, 9} Ullmer C.... Luebbert H. (FEBS Lett. 1995)
Association study of the serotoninergic system in migraine in the Spanish population. (PubMed id 19455600)^{1, 4} Corominas R....Cormand B. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010)
Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. (PubMed id 20010835)^{1, 4} Hancock D.B....London S.J. (Nat. Genet. 2010)
Genome-wide association study identifies five loci associated with lung function. (PubMed id 20010834)^{1, 4} Repapi E....Tobin M.D. (Nat. Genet. 2010)
Lack of association between HTR4 gene polymorphisms and schizophrenia in case-control and family-based samples. (PubMed id 19892407)^{1, 4} Hirata Y....Kennedy J.L. (Psychiatry Res 2010)
Candidate gene analysis in an on-going genome-wide association study of attention-deficit hyperactivity disorder: suggestive association signals in ADRA1A. (PubMed id 19352218)^{1, 4} Elia J....Hakonarson H. (Psychiatr. Genet. 2009)
Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis. (PubMed id 19156168)^{1, 4} Need A.C....Goldstein D.B. (Eur. J. Hum. Genet. 2009)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 3360	HGNC: 5299	AceView: HTR4andKIAA1985	Ensembl:ENSG00000164270	euGenes: HUgn3360
ECgene: HTR4	Kegg: 3360	H-InvDB: HTR4

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for HTR4	Pharmacogenomics, SNPs, Pathways

Intellectual Property for HTR4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for HTR4 gene:
Search GeneIP for patents involving HTR4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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HTR4 Gene

5-Hydroxytryptamine (Serotonin) Receptor 4, G Protein-Coupled

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HTR4 Gene

5-Hydroxytryptamine (Serotonin) Receptor 4, G Protein-Coupled

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