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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

HTR4 Gene

protein-coding GIFtS: 70
GCID: GC05M147810

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

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

Alzheimer's & Parkinson's Diseases Congress

31 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)
About This Section

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

Export aliases for HTR4 gene to outside databases

Previous GC identifers: GC05M147904 GC05M148425 GC05M147859 GC05M142977

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

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 hereditary diffuse leukoencephalopathy with spheroids, and constipation, and among its related super-pathways are Class A/1 (Rhodopsin-like receptors) and Monoamine GPCRs. GO annotations related to this gene include serotonin receptor activity. An important paralog of this gene is HTR6.

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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000005.9 NT_029289.11 NC_018916.2

Regulatory elements:

SABiosciences 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 SABiosciences Chromatin IP Primers for HTR4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MAXQB 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, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

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)

Subcellular location: 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)

Secondary accessions: Q546Q1 Q684M0 Q712M9 Q96KH9 Q96KI0 Q9H199 Q9NY73 Q9UBM6 Q9UBT4 Q9UE22 Q9UE23

Q9UQR6

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

(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:

View modification sites using PhosphoSitePlus

View neXtProt modification sites for NX_Q13639

HTR4 Protein expression data from MOPED¹, PaxDb² and MAXQB³ : About this image

REFSEQ proteins (5 alternative transcripts):

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

ENSEMBL proteins:

ENSP00000428320 ENSP00000430874 ENSP00000430979 ENSP00000435904 ENSP00000427913

ENSP00000367120 ENSP00000353915 ENSP00000430451 ENSP00000429634 ENSP00000346156

ENSP00000314906 ENSP00000355037

Reactome Protein details: Q13639
Human Recombinant Protein Products for HTR4:

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	Browse ProSpec Recombinant Proteins
	Cloud-Clone Corp. Proteins for HTR4

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (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 to plasma membrane	IEA	--
GO:0016020	membrane	IDA	16102731

HTR4 for ontologies About GeneDecksing

HTR4 Antibody Products:

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Assay Products for HTR4:

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	Cloud-Clone Corp. ELISAs for HTR4 Cloud-Clone Corp. CLIAs for HTR4

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

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

HTR4 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
About This Section

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 (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004683	calmodulin-dependent protein kinase activity	--	--
GO:0004930	G-protein coupled receptor activity	--	--
GO:0004993	serotonin receptor activity	IDA	16102731

HTR4 for ontologies About GeneDecksing

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

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

HTR4 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-out Htr4^tm1Comp for HTR4

inGenious Targeting Laboratory - Custom generated mouse model solutions for HTR4

inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for HTR4

miRNA Products:
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat HTR4
		8/43 QIAGEN miScript miRNA 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:		Browse for Gene Knock-down Tools from EMD Millipore
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		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)
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		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat HTR4

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		Sirion Biotech Customized stable knockdown cell line services for HTR4 Customized inducible knockdown cell line services for HTR4 Customized stable overexpressing cell line services for HTR4 Customized inducible overexpressing cell line services for HTR4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HTR4

(Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
About This Section

SuperPaths for HTR4 About (see all 9)

See pathways by source

SuperPath

Contained pathways About

Class A/1 (Rhodopsin-like receptors)

	Class A/1 (Rhodopsin-like receptors)	0.71			GPCRs, Class A Rhodopsin-like	0.41
	GPCR ligand binding	0.71			Neuroactive ligand-receptor interaction	0.37

Monoamine GPCRs

	Monoamine GPCRs	0.79			Serotonin receptors	0.36
	Amine ligand-binding receptors	0.79			Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics	0.33

Signaling by GPCR

	Signaling by GPCR	0.90			Signal Transduction	0.55
	GPCR downstream signaling	0.90

Development Ligand-independent activation of ESR1 and ESR2

Transcription CREB pathway

0.93

Development Ligand-independent activation of ESR1 and ESR2

0.34

CREB Pathway

Intracellular Calcium Signaling

0.50

Pathways by source See SuperPaths
Show all pathways

2 EMD Millipore Pathways for HTR4

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

1 Downloadable PowerPoint Slide of QIAGEN 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

5/8 Reactome Pathways for HTR4 (see all 8)

	GPCR downstream signaling
	Signaling by GPCR
	GPCR ligand binding
	Class A/1 (Rhodopsin-like receptors)
	Serotonin receptors

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

HTR4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for HTR4

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

5/66 Interacting proteins for HTR4 (Q13639^{2, 3} ENSP00000353915⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 66)

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
ADRB1	ENSP00000358301⁴	STRING: ENSP00000358301

About this table

Gene Ontology (GO): 5/9 biological process terms (GO ID links to tree view) (see all 9): 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

HTR4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, IUPHAR, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

HTR4 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

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

10/28 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

10/28 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)

Search CenterWatch for drugs/clinical trials and news about HTR4 / 5HT4R

(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,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for HTR4 gene (6 alternative transcripts):

NM_000870.5 NM_001040169.2 NM_001040172.2 NM_001040173.2 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:
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		8/43 QIAGEN miScript miRNA 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:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene RNAi products in human, mouse, rat for HTR4
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat HTR4
		Sirion Biotech Custom design and validation of potent shRNA sequences against 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
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat HTR4

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		SABiosciences RT² qPCR Primer Assay in human, mouse, rat HTR4
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat HTR4
		QIAGEN 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.108819 DT.91661182 DT.102830595 DT.99937173 DT.120832090 DT.95149585 DT.101972406

DT.91661178 DT.95332349

24/113 AceView cDNA sequences (see all 113):

CR608321 BC074755 Y09586 CR595950 AY341075 AK124854 NM_024577 AJ131726

BI054444 BX283793 AJ131725 AK095223 AJ519673 Y10437 Y13584 BE302852

AJ633645 NM_199453 AJ278979 AI033298 AJ278980 BQ213149 BX386178 CB141690

GeneLoc Exon Structure

5/9 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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

HTR4 expression in normal human tissues (normalized intensities) HTR4 embryonic expression: see
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

5/16 selected tissues (see all 16) fully expand


Brain (Nervous System) fully expand to see all 37 entries
Thalamus
Substantia Nigra

Spinal Cord (Nervous System) fully expand to see all 4 entries
Dorsal Horn

Reproductive System (Reproductive System) fully expand to see all 4 entries
uterus, post-menopause ; glandular cells

Testis (Reproductive System) fully expand to see all 3 entries
Leydig Cells Testis Interstitium
seminal vesicle ; glandular cells

Breast
breast ; myoepithelial cells

See HTR4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for HTR4

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

SABiosciences Expression via Pathway-Focused 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)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for HTR4 gene from 5/11 species (see all 11) 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	83(n) 89.8(a)		416150 XM_414481.3 XP_414481.3
lizard (Anolis carolinensis)	Reptilia	HTR4⁶	5-hydroxytryptamine (serotonin) receptor 4, G prot...	85(a)	1 ↔ 1	2(121764217-122004739)
zebrafish (Danio rerio)	Actinopterygii	LOC559089¹	5-hydroxytryptamine receptor 4-like	64.96(n) 68.38(a)		559089 XM_682395.1 XP_687487.1
fruit fly (Drosophila melanogaster)	Insecta	CG6919³ oa2¹	G-protein coupled receptor protein signaling pathway more³ octopamine receptor 2¹	42(a) (best of 3)³ 53.31(n)¹ 46.69(a)¹		94B2³ 42652¹ NM_001170219.1¹ NP_001163690.1¹

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)
About This Section

Paralogs for HTR4 gene

HTR6² TAAR2² TAAR9² TAAR8² HRH2² ADRA1A² TAAR5² TAAR6²

ADRB1² ADRA1B² DRD1² TAAR1² ADRB2² ADRB3² DRD5² ADRA1D²

18/29 SIMAP similar genes for HTR4 using alignment to 4 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

HTR4 for paralogs About GeneDecksing

(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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

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	--	--	--	--
VAR_067412⁴		--	--	see VAR_067412	2	S L	mis⁴		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	--	--	--	--

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

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

HTR4 for disorders           About GeneDecksing

OMIM gene information: 602164    OMIM disorders: --

20/31 diseases for HTR4 (see all 31):    About MalaCards

hereditary diffuse leukoencephalopathy with spheroids constipation dyspepsia irritable bowel syndrome

obstructive lung disease congenital heart block adrenal adenoma hyperaldosteronism

gastroparesis ileus chronic fatigue syndrome cushing's syndrome

attention deficit hyperactivity disorder obesity, association with diarrhea duodenitis

colon adenocarcinoma schizophrenia bipolar disorder cytochrome p450

4 diseases from the University of Copenhagen DISEASES database for HTR4:

Constipation Gastroparesis Functional colonic disease Irritable bowel syndrome

Congresses - knowledge worth sharing:
Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

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)
About This Section

PubMed articles for HTR4 gene, integrated from 9 sources (see all 241):
(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. (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. (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. (1998)
Expression of serotonin receptor mRNAs in blood vessels. (PubMed id 7656980)^{1, 2, 9} Ullmer C.... Luebbert H. (1995)
Association study of the serotoninergic system in mig raine in the Spanish population. (PubMed id 19455600)^{1, 4} Corominas R....Cormand B. (2010)
Meta-analyses of genome-wide association studies iden tify multiple loci associated with pulmonary function. (PubMed id 20010835)^{1, 4} Hancock D.B....London S.J. (2010)
Genome-wide association study identifies five loci as sociated with lung function. (PubMed id 20010834)^{1, 4} Repapi E....Rudnicka A.R. (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. (2009)
Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis. (PubMed id 19156168)^{1, 4} Need A.C....Goldstein D.B. (2009)
Case-control association study of 65 candidate genes revealed a possible association of a SNP of HTR5A to be a factor susceptible to bipolar disease in Bulgarian population. (PubMed id 19328558)^{1, 4} Yosifova A....Nakamura Y. (2009)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		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)
About This Section

Entrez Gene: 3360	HGNC: 5299	AceView: HTR4andKIAA1985	Ensembl:ENSG00000164270	euGenes: HUgn3360
ECgene: HTR4	Kegg: 3360	H-InvDB: HTR4

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

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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