HTR4: 5-Hydroxytryptamine Receptor 4
Serotonin Receptor 4 – Gene, Function, and Clinical Significance
Gene Information Card
| Symbol | HTR4 |
|---|---|
| Full Name | 5-hydroxytryptamine receptor 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q32 |
| NCBI Gene ID | 3360 ncbi.nlm.nih.gov/gene/3360 |
| Ensembl ID | ENSG00000164270 |
| UniProt ID | Q13639 |
| OMIM ID | 602164 |
| HGNC ID | 5299 |
| Aliases | 5-HT4, 5-HT4R, HTR4A, HTR4B |
Description
The HTR4 gene encodes the 5-hydroxytryptamine receptor 4 (5-HT4), a G protein-coupled receptor for serotonin. It is involved in neurotransmission, gastrointestinal motility, and cardiac function. Alternative splicing generates multiple isoforms with distinct tissue distributions and signaling properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Irritable Bowel Syndrome (IBS) | Altered 5-HT4 signaling affects gut motility and secretion; receptor agonists used therapeutically. | ClinVar, OMIM |
| Alzheimer Disease | HTR4 polymorphisms associated with cognitive decline; receptor modulation may influence amyloid pathology. | NCBI Gene, OMIM |
| Gastroesophageal Reflux Disease (GERD) | 5-HT4 agonists enhance lower esophageal sphincter tone and accelerate gastric emptying. | ClinVar |
| Cardiac Arrhythmia | 5-HT4 activation in atrial myocytes can trigger tachyarrhythmias; rare variants linked to atrial fibrillation. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cortex) | 5.2 | Medium |
| Stomach | 8.1 | High |
| Small intestine | 7.6 | High |
| Colon | 6.9 | High |
| Heart (atrium) | 3.4 | Low |
| Liver | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 4.5 | Neuronal model |
| Caco-2 (colorectal) | 6.2 | Intestinal epithelial model |
| HepG2 (hepatocellular) | 0.5 | Low expression |
| HEK293 (embryonic kidney) | 1.2 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.116C>T (p.Pro39Leu) | Missense | 0.01% | Reduced receptor activity in vitro |
| c.452G>A (p.Arg151His) | Missense | 0.005% | Altered ligand binding |
| c.788_789del (p.Leu263fs) | Frameshift | <0.001% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants (e.g., p.Leu263fs) lead to truncated, non-functional receptor.
Gain of Function (GOF)
Not well documented; some missense variants may increase constitutive activity.
Dominant Negative (DN)
Not reported for HTR4.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • serotonin binding |
| • serotonin receptor activity | • adenylate cyclase activation |
| • positive regulation of cAMP-mediated signaling | • synaptic transmission |
| • serotonergic | • regulation of gastrointestinal motility |
| • positive regulation of heart rate |
Pathways
• Serotonin receptor signaling (KEGG: hsa04726)
• GPCR downstream signaling (Reactome: R-HSA-388396)
• cAMP signaling pathway (KEGG: hsa04024)
Protein Summary
The 5-HT4 receptor is a 387-amino acid (canonical isoform) GPCR that couples primarily to Gs, stimulating adenylate cyclase and increasing intracellular cAMP. It is expressed in the brain, gastrointestinal tract, and heart. The receptor modulates neurotransmitter release, smooth muscle contraction, and cardiac chronotropy. Multiple splice variants (HTR4A, HTR4B, etc.) differ in the C-terminal tail, affecting desensitization and trafficking.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HTR4 Knockout HEK293 Cell Line | EDJ-KQ1557 | Human | 3360 | Details Get a Quote |
| HTR4 Knockout A-549 Cell Line | EDJ-KQ18370 | Human | 3360 | Details Get a Quote |
| HTR4 Knockout HeLa Cell Line | EDJ-KQ53595 | Human | 3360 | Details Get a Quote |
| HTR4 Knockout HCT 116 Cell Line | EDJ-KQ70545 | Human | 3360 | Details Get a Quote |
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