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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]
HTR4 (5-Hydroxytryptamine Receptor 4) is a Protein Coding gene. Diseases associated with HTR4 include Irritable Bowel Syndrome and Constipation. Among its related pathways are Neuroscience and Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and trace-amine receptor activity. An important paralog of this gene is DRD5.
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.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH05J148654 | Promoter | 0.8 | EPDnew Ensembl | 610.7 | +23.0 | 23034 | 0.8 | EZH2 SPI1 | HTR4 ENSG00000253297 lnc-HTR4-2 piR-48553-259 FBXO38 | |
GH05J148653 | Promoter | 0.4 | EPDnew | 610.7 | +23.6 | 23645 | 0.1 | EZH2 | HTR4 ENSG00000253297 lnc-HTR4-2 piR-48553-259 FBXO38 | |
GH05J148620 | Enhancer | 0.8 | Ensembl ENCODE | 10.4 | +56.8 | 56834 | 2.4 | JUND HMBOX1 EGR1 RUNX3 NCOR1 EHMT2 TAL1 BHLHE40 DPF2 HDAC2 | HTR4 ENSG00000247199 FBXO38 ENSG00000253297 piR-61532-254 lnc-HTR4-2 | |
GH05J148699 | Enhancer | 0.3 | Ensembl | 11.7 | -22.4 | -22366 | 1.2 | SPI1 | HTR4 piR-48369-165 piR-61021-008 ADRB2 | |
GH05J148659 | Enhancer | 0.9 | Ensembl ENCODE | 0.4 | +17.0 | 17017 | 2.2 | LEF1 JUND PKNOX1 DPF2 HDAC1 SOX6 TCF12 EP300 CTBP1 FOXK2 | ENSG00000253297 piR-48553-259 HTR4 lnc-HTR4-2 FBXO38 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004930 | G protein-coupled receptor activity | IBA | 21873635 |
GO:0004993 | G protein-coupled serotonin receptor activity | IDA | 16102731 |
GO:0005515 | protein binding | IPI | 28298427 |
GO:0030594 | neurotransmitter receptor activity | IBA | 21873635 |
GO:0051378 | serotonin binding | IBA | 21873635 |
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 | TAS,IBA | 21873635 |
GO:0016020 | membrane | IDA | 16102731 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Peptide ligand-binding receptors | ||
2 | Monoamine GPCRs |
.75
|
|
3 | Signaling by GPCR | ||
4 | Development Ligand-independent activation of ESR1 and ESR2 |
Development Ligand-independent activation of ESR1 and ESR2
.35
|
Transcription CREB pathway
.34
|
5 | Ca, cAMP and Lipid Signaling |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0007165 | signal transduction | IEA | -- |
GO:0007186 | G protein-coupled receptor signaling pathway | TAS | -- |
GO:0007187 | G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | TAS,IBA | 21873635 |
GO:0007198 | adenylate cyclase-inhibiting serotonin receptor signaling pathway | IBA | 21873635 |
GO:0007268 | chemical synaptic transmission | IBA | 21873635 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Cisapride | Approved, Investigational, Withdrawn | Pharma | Agonist, Partial agonist, Target, agonist | 5-HT4 agonist; stimulates intestinal ACh release | 5 | |
Tegaserod | Approved, Investigational, Withdrawn | Pharma | Antagonist, Agonist, Partial agonist, Target, antagonist, partial agonist, agonist | 27 | ||
Tropisetron | Approved, Investigational | Pharma | Antagonist, antagonist | 27 | ||
Prucalopride | Approved | Pharma | Agonist, Partial agonist, Target, agonist | 5-HT4A and 5-HT4B receptor agonist | 55 | |
Ondansetron | Approved | Pharma | Target, agonist | 409 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
5-HT |
|
Agonist, Full agonist, Inhibitor, Inhibition |
|
|||
2-[1-(4-Piperonyl)piperazinyl]benzothiazole |
|
155106-73-3 |
|
|
Compound | Action | Cas Number |
---|---|---|
2-[1-(4-Piperonyl)piperazinyl]benzothiazole | 5-HT4 agonist. Also 5-HT3 antagonist | 155106-73-3 |
Cisapride | 5-HT4 agonist; stimulates intestinal ACh release | 81098-60-4 |
Mosapride citrate | 5-HT4 agonist and 5-HT3 antagonist | 112885-42-4 |
RS 67333 hydrochloride | 5-HT4 partial agonist | 168986-60-5 |
RS 67506 hydrochloride | 5-HT4 partial agonist | 168986-61-6 |
Compound | Action | Cas Number |
---|---|---|
Amitriptyline HCl | Serotonin /norepinephrine receptor/5-HT4/5-HT2 inhibitor | 549-18-8 |
Asenapine | Inhibits adrenergic receptor/5-HT receptor | 85650-56-2 |
Bilobalide | Neuroprotective agent | 33570-04-6 |
BIMU 8 | Potent 5-HT4 receptor full agonist | 134296-40-5 |
Blonanserin | Atypical antipsychotic | 132810-10-7 |
BTS 54-505 hydrochloride | Potent SNRI,sibutramine metabolite | 84484-78-6 |
Cisapride | 81098-60-4 | |
CJ 033466 | 519148-48-2 | |
Clomipramine HCl | SERT/NET dopamine transporter (DAT) blocker | 17321-77-6 |
Clozapine N-oxide | Metabolite of clozapine | 34233-69-7 |
Dapoxetine HCl | Selective serotonin reuptake inhibitor | 129938-20-1 |
Desvenlafaxine | 93413-62-8 | |
Desvenlafaxine Succinate | 386750-22-7 | |
Dihydroergotamine mesylate | 6190-39-2 | |
DOB hydrochloride | 29705-96-2 | |
DOI hydrochloride | 42203-78-1 | |
Duloxetine HCl | 136434-34-9 | |
Escitalopram Oxalate | Serotonin(5-HT) reuptake (SSRI) inhibitor | 219861-08-2 |
Fenspiride HCl | 5053-08-7 | |
Fluoxetine HCl | Serotonin reuptake inhibitor,selective | 56296-78-7 |
Fluvoxamine maleate | Serotonin reuptake inhibitor,selective,antidepressant | 61718-82-9 |
GR 113808 | 144625-51-4 | |
GR 125487 sulfamate | 859502-43-5 | |
GR 46611 | 185259-85-2 | |
Ketanserin | 74050-98-9 | |
LY310762 | 192927-92-7 | |
m-CPP hydrochloride | 13078-15-4 | |
Methysergide maleate | 129-49-7 | |
Milnacipran HCl | 101152-94-7 | |
ML 10302 hydrochloride | 186826-17-5 | |
Mosapride | 112885-41-3 | |
Mosapride Citrate | 5-HT receptor agonist | 112885-42-4 |
MS 245 oxalate | 275363-58-1 | |
NAD 299 hydrochloride | 184674-99-5 | |
Naratriptan | 143388-64-1 | |
Olanzapine | 132539-06-1 | |
Ondansetron | 99614-02-5 | |
Palonosetron HCl | 135729-62-3 | |
Pizotifen Malate | 5189-11-7 | |
Prucalopride Succinat | 179474-85-2 | |
Risperidone | SR-2A inhibitor | 106266-06-2 |
Rizatriptan Benzoate | 145202-66-0 | |
RS 23597-190 hydrochloride | 149719-06-2 | |
RS 39604 hydrochloride | 167710-87-4 | |
RS 67333 hydrochloride | 168986-60-5 | |
RS 67506 hydrochloride | 168986-61-6 | |
Sarpogrelate hydrochloride | 135159-51-2 | |
SB 200646 hydrochloride | 143797-62-0 | |
SB 203186 hydrochloride | 207572-69-8 | |
SB 204070 | 148688-01-1 | |
SB 242084 | 1215566-78-1 | |
SB 243213 dihydrochloride | 200940-23-4 | |
SB 258719 hydrochloride | 1217674-10-6 | |
SDZ 205-557 hydrochloride | 1197334-02-3 | |
SEA0400 | Specific inhibitor of Na+/Ca2+ exchange | 223104-29-8 |
Sertraline HCl | 79559-97-0 | |
Tandospirone | Anxiolytic and antidepressant reagent | 87760-53-0 |
Tegaserod maleate | 189188-57-6 | |
Tianeptine sodium | 5-HT uptake facilitator,selective,antidepressant | 30123-17-2 |
Trazodone HCl | Antidepressant | 25332-39-2 |
Tropisetron | 105826-92-4 | |
Urapidil HCl | 64887-14-5 | |
Venlafaxine | Dual serotonin/noradrenalin re-uptake inhibitor | 99300-78-4 |
Vortioxetine | 5-HT receptors antagonist | 508233-74-7 |
Vortioxetine (Lu AA21004) HBr | 5-HT receptor modulator, antidepressant and anxiolytic | 960203-27-4 |
VUF 10166 | 155584-74-0 | |
WY 45233 succinate | 448904-47-0 | |
Ziprasidone HCl | Serotonin and dopamine receptor antagonist | 122883-93-6 |
Ziprasidone hydrochloride monohydrate | 5-HT (serotonin)/dopamine receptor antagonist | 138982-67-9 |
Zolmitriptan | 139264-17-8 |
ExUns: | 1a | · | 1b | ^ | 2a | · | 2b | · | 2c | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7a | · | 7b | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14a | · | 14b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | ||||||||||||||||||||||||||||||||
SP2: | - | - | |||||||||||||||||||||||||||||||||||
SP3: | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||
SP4: | - | - | - | ||||||||||||||||||||||||||||||||||
SP5: | - | - | - | - | |||||||||||||||||||||||||||||||||
SP6: | - | - | - | - | - | ||||||||||||||||||||||||||||||||
SP7: | - | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||
SP8: | - | ||||||||||||||||||||||||||||||||||||
SP9: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | HTR4 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | HTR4 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | HTR4 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | HTR4 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Htr4 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Htr4 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | HTR4 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | HTR4 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | HTR4 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100493952 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | HTR4 31 |
|
OneToOne | |
LOC556843 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | oa2 30 31 |
|
ManyToMany | |
CG6919 32 |
|
|
|||
CG6989 32 |
|
|
|||
DopR 32 |
|
|
|||
Octbeta2R 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 05 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
709214 | Likely Benign: not provided | 148,550,246(-) | C/T | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT | |
776075 | Benign: not provided | 148,483,255(-) | C/T | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,INTRON_VARIANT | |
780569 | Benign: not provided | 148,484,289(-) | T/C | SYNONYMOUS_VARIANT,INTRON_VARIANT | |
792016 | Benign: not provided | 148,509,464(-) | A/G | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT | |
rs199508638 | - | p.Ser27Leu |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv3305996 | CNV | mobile element insertion | 20981092 |
esv3406555 | CNV | insertion | 20981092 |
esv3607115 | CNV | loss | 21293372 |
esv3607116 | CNV | loss | 21293372 |
esv3607118 | CNV | loss | 21293372 |
esv3607119 | CNV | loss | 21293372 |
nsv1152791 | CNV | duplication | 26484159 |
nsv328933 | CNV | deletion | 16902084 |
nsv523792 | CNV | loss | 19592680 |
nsv830516 | CNV | loss | 17160897 |
Disorder | Aliases | PubMed IDs |
---|---|---|
irritable bowel syndrome |
|
|
constipation |
|
|
colonic pseudo-obstruction |
|
|
gastrointestinal system disease |
|
|
adrenal adenoma |
|
|