HTR4 (5-hydroxytryptamine receptor 4)

Gene

• Entrez ID: 3360
• Gene name: 5-hydroxytryptamine receptor 4
• Gene symbol: HTR4
• Synonyms (NCBI Gene): 5-HT4, 5-HT4R
• Chromosome: 5
• Chromosome location: 5q32
• 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 bot

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1057276	hsa-miR-1299	CLIP-seq
MIRT1057277	hsa-miR-216a	CLIP-seq
MIRT1057278	hsa-miR-3126-3p	CLIP-seq
MIRT1057279	hsa-miR-326	CLIP-seq
MIRT1057280	hsa-miR-330-5p	CLIP-seq
MIRT1057281	hsa-miR-342-3p	CLIP-seq
MIRT1057282	hsa-miR-4717-3p	CLIP-seq
MIRT1057283	hsa-miR-496	CLIP-seq
MIRT1057284	hsa-miR-653	CLIP-seq
MIRT1057285	hsa-miR-671-5p	CLIP-seq
MIRT1057286	hsa-miR-760	CLIP-seq
MIRT1057287	hsa-miR-875-3p	CLIP-seq
MIRT1057288	hsa-miR-1205	CLIP-seq
MIRT1057289	hsa-miR-1275	CLIP-seq
MIRT1057290	hsa-miR-1909	CLIP-seq
MIRT1057291	hsa-miR-3189-3p	CLIP-seq
MIRT1057292	hsa-miR-3662	CLIP-seq
MIRT1057293	hsa-miR-4300	CLIP-seq
MIRT1057294	hsa-miR-4525	CLIP-seq
MIRT1057295	hsa-miR-4665-5p	CLIP-seq
MIRT1057296	hsa-miR-4668-5p	CLIP-seq
MIRT1057297	hsa-miR-4723-5p	CLIP-seq
MIRT1057298	hsa-miR-558	CLIP-seq
MIRT1057299	hsa-miR-625	CLIP-seq
MIRT1057300	hsa-miR-920	CLIP-seq
MIRT1057301	hsa-miR-939	CLIP-seq
MIRT2013093	hsa-miR-149	CLIP-seq
MIRT2013094	hsa-miR-3064-5p	CLIP-seq
MIRT2013095	hsa-miR-4794	CLIP-seq
MIRT1057276	hsa-miR-1299	CLIP-seq
MIRT1057278	hsa-miR-3126-3p	CLIP-seq
MIRT1057285	hsa-miR-671-5p	CLIP-seq
MIRT2245380	hsa-miR-940	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003008	Process	System process	IEA
GO:0004930	Function	G protein-coupled receptor activity	IEA
GO:0004993	Function	G protein-coupled serotonin receptor activity	IBA
GO:0004993	Function	G protein-coupled serotonin receptor activity	IDA	9603189, 10821780, 16102731, 35714614
GO:0004993	Function	G protein-coupled serotonin receptor activity	IEA
GO:0004993	Function	G protein-coupled serotonin receptor activity	TAS	9603189
GO:0005515	Function	Protein binding	IPI	28298427
GO:0005737	Component	Cytoplasm	IDA	15925089
GO:0005768	Component	Endosome	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IC	33481771
GO:0005886	Component	Plasma membrane	IDA	10821780, 22448645
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	9276448
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	9351641
GO:0007187	Process	G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	IBA
GO:0007187	Process	G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	TAS	9603189
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA	9603189
GO:0007192	Process	Adenylate cyclase-activating serotonin receptor signaling pathway	IDA	17110384
GO:0007192	Process	Adenylate cyclase-activating serotonin receptor signaling pathway	IDA	35714614
GO:0007198	Process	Adenylate cyclase-inhibiting serotonin receptor signaling pathway	IBA
GO:0007268	Process	Chemical synaptic transmission	IBA
GO:0007268	Process	Chemical synaptic transmission	IEA
GO:0010008	Component	Endosome membrane	IEA
GO:0016020	Component	Membrane	IDA	16102731
GO:0016020	Component	Membrane	IEA
GO:0030277	Process	Maintenance of gastrointestinal epithelium	IEA
GO:0030425	Component	Dendrite	IBA
GO:0030594	Function	Neurotransmitter receptor activity	IBA
GO:0032098	Process	Regulation of appetite	IEA
GO:0051378	Function	Serotonin binding	IBA
GO:0070254	Process	Mucus secretion	IEA
GO:0070254	Process	Mucus secretion	IMP	17058067
GO:0098794	Component	Postsynapse	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099589	Function	Serotonin receptor activity	IDA	33481771, 35714614
GO:0120056	Process	Large intestinal transit	IDA	33481771
GO:0150052	Process	Regulation of postsynapse assembly	IEA

Other IDs

• MIM: 602164
• HGNC: 5299
• e!Ensembl: ENSG00000164270

Protein

• UniProt ID: Q13639
• Protein name: 5-hydroxytryptamine receptor 4 (5-HT-4) (5-HT4) (Serotonin receptor 4)
• Protein function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:10821780, PubMed:16102731, PubMed:35714614, PubMed:9603189). Ligand binding causes a conform
• PDB: 5EM9, 7XT8, 7XT9, 7XTA
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00001	7tm_1	36 → 312	7 transmembrane receptor (rhodopsin family)	Family

• Tissue specificity: TISSUE SPECIFICITY: [Isoform 5-HT4(A)]: Expressed in ileum, brain, and atrium, but not in the ventricle. {ECO:0000269|PubMed:15118808}.; TISSUE SPECIFICITY: [Isoform 5-HT4(E)]: Mainly expressed in atria and cardiac ventricle. {ECO:0000269|PubMed:15118808}
• Sequence:

  MDKLDANVSSEEGFGSVEKVVLLTFLSTVILMAILGNLLVMVAVCWDRQLRKIKTNYFIV
  SLAFADLLVSVLVMPFGAIELVQDIWIYGEVFCLVRTSLDVLLTTASIFHLCCISLDRYY
  AICCQPLVYRNKMTPLRIALMLGGCWVIPTFISFLPIMQGWNNIGIIDLIEKRKFNQNSN
  STYCVFMVNKPYAITCSVVAFYIPFLLMVLAYYRIYVTAKEHAHQIQMLQRAGASSESRP
  QSADQHSTHRMRTETKAAKTLCIIMGCFCLCWAPFFVTNIVDPFIDYTVPGQVWTAFLWL
  GYINSGLNPFLYAFLNKSFRRAFLIILCCDDERYRRPSILGQTVPCSTTTINGSTHVLRD
  AVECGGQWESQCHPPATSPLVAAQPSDT

• Sequence length: 388

Pathways

KEGG:

Calcium signaling pathway
cAMP signaling pathway
Neuroactive ligand-receptor interaction
Serotonergic synapse

Reactome:

Serotonin receptors
G alpha (s) signalling events
ADORA2B mediated anti-inflammatory cytokines production

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANOREXIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ARRHYTHMIAS, CARDIAC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIAC ARRHYTHMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CEREBROVASCULAR ACCIDENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC LUNG DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOR VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSIVE DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung adenocarcinoma	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL DEPRESSION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOOD DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANCREATITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PELVIC ORGAN PROLAPSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESPIRATORY SYSTEM DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STROKE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acth-Independent Macronodular Adrenal Hyperplasia	Cushing`s Syndrome	BEFREE	17218722		★☆☆☆☆ Found in Text Mining only
Acute Cerebrovascular Accidents	Stroke	CTD_human_DG	7886817		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	LHGDN	16322401		★☆☆☆☆ Found in Text Mining only
Adrenal Gland Pheochromocytoma	Adrenal Gland Pheochromocytoma	BEFREE	18948374		★☆☆☆☆ Found in Text Mining only
Anorexia	Anorexia	CTD_human_DG	15146954		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anxiety	Anxiety disorder	Pubtator	31977880	Associate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	21382128		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Fibrillation	Atrial Fibrillation	BEFREE	11215536, 17418812		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Fibrillation	Atrial Fibrillation	CTD_human_DG	7886817		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	16563621		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	31977880	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	19086034		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	PSYGENET_DG	12399948		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar disorder	Pubtator	20197377	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cerebrovascular accident	Stroke	CTD_human_DG	7886817		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Choriocarcinoma	Choriocarcinoma	BEFREE	11716477		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	21965014, 24286382		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	GWASCAT_DG	28166215, 30804561, 30940143		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognitive disorder	BEFREE	31615585		★☆☆☆☆ Found in Text Mining only
Complete atrioventricular block	Complete Atrioventricular Block	BEFREE	16960982		★☆☆☆☆ Found in Text Mining only
Congenital adrenal hyperplasia	Congenital adrenal hyperplasia	CTD_human_DG	17218722		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	15365689, 17936780		★☆☆☆☆ Found in Text Mining only
Conn Adenoma	Conn Adenoma	BEFREE	17911395, 28870781		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	Pubtator	35151267	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cushing Syndrome	Cushing`s Syndrome	BEFREE	14557431		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	PSYGENET_DG	19476548, 20060867, 20962330, 25522384		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive disorder	Mental Depression	BEFREE	25522384, 26821757, 31615585		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive Disorder	Major depressive disorder	Pubtator	31977880	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	31152805		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Diseases	Gastrointestinal disease	Pubtator	20197377	Associate	★☆☆☆☆ Found in Text Mining only
Gastroparesis	Gastroparesis	BEFREE	30934667		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	24358143	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart Diseases	LHGDN	17603679		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	15365689, 17936780		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	31615585		★☆☆☆☆ Found in Text Mining only
Irritable Bowel Syndrome	Irritable Bowel Syndrome	BEFREE	21615623, 29089619		★☆☆☆☆ Found in Text Mining only
Irritable Bowel Syndrome	Irritable bowel syndrome	Pubtator	29089619	Associate	★☆☆☆☆ Found in Text Mining only
Left Ventricular Hypertrophy	Left Ventricular Hypertrophy	BEFREE	17936780		★☆☆☆☆ Found in Text Mining only
Lung Diseases	Lung disease	Pubtator	20010835	Associate	★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	25522384		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	8661150		★☆☆☆☆ Found in Text Mining only
Memory Disorders	Memory Disorders	BEFREE	12543273		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	PSYGENET_DG	19476548, 20060867, 20962330, 25522384		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mental Depression	Mental Depression	BEFREE	25522384, 26821757, 31615585		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mood Disorders	Mood Disorder	BEFREE	12399948		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mood Disorders	Mood Disorder	LHGDN	12399948		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mood Disorders	Mood Disorder	PSYGENET_DG	12399948, 20962330		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neoplasms	Neoplasms	BEFREE	18948374		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	23474291, 26821757		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	34872017	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Failure, Premature	Ovarian Failure	BEFREE	30472681		★☆☆☆☆ Found in Text Mining only
Paroxysmal atrial fibrillation	Paroxysmal atrial fibrillation	CTD_human_DG	7886817		★☆☆☆☆ Found in Text Mining only
Pheochromocytoma	Pheochromocytoma	BEFREE	18948374		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	34512870	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	21965014, 23890215, 34233669	Associate	★☆☆☆☆ Found in Text Mining only
Respiratory Tract Diseases	Respiratory system infectious disease	Pubtator	20010834	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	12399948, 12898568, 15205874, 19892407, 22842674		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	12399948, 12898568, 19892407, 22842674		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	LHGDN	12898568		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	20197377	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Testicular regression syndrome	Testicular regression syndrome	BEFREE	18359159		★☆☆☆☆ Found in Text Mining only
Torsades de Pointes	Torsades de Pointes	BEFREE	17785939		★☆☆☆☆ Found in Text Mining only
Unipolar Depression	Mental Depression	BEFREE	25522384		★☆☆☆☆ Found in Text Mining only