HTR6 (5-Hydroxytryptamine Receptor 6)
Serotonin Receptor 6: A G Protein-Coupled Receptor in Neurotransmission and CNS Disorders
Gene Information Card
| Symbol | HTR6 |
|---|---|
| Full Name | 5-hydroxytryptamine receptor 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 3362 ncbi.nlm.nih.gov/gene/3362 |
| Ensembl ID | ENSG00000172116 |
| UniProt ID | P50406 |
| OMIM ID | 601109 |
| HGNC ID | 5299 |
| Aliases | 5-HT6, 5-HT6R |
Description
The HTR6 gene encodes the 5-hydroxytryptamine receptor 6 (5-HT6), a G protein-coupled receptor (GPCR) that binds serotonin (5-HT). It is primarily expressed in the central nervous system, particularly in regions involved in cognition, mood, and appetite. Activation of HTR6 stimulates adenylate cyclase via Gs protein, increasing intracellular cAMP. The receptor is implicated in learning, memory, and neuropsychiatric disorders. It is a target for antipsychotic and cognitive-enhancing drugs.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | Dysregulation of HTR6 signaling may impair cholinergic neurotransmission and cognitive function; receptor antagonists improve memory in preclinical models. | NCBI Gene, OMIM |
| Schizophrenia | HTR6 polymorphisms are associated with altered receptor expression; antagonists are used as adjunctive therapy for cognitive symptoms. | NCBI Gene, ClinVar |
| Obesity | HTR6 activation influences appetite regulation; antagonists reduce food intake in animal studies. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (hippocampus) | 10.8 | High |
| Brain (striatum) | 9.2 | High |
| Spinal cord | 3.1 | Low |
| Testis | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.7 | Neuronal model |
| U-87 MG (glioblastoma) | 2.3 | Low expression |
| HEK293 (embryonic kidney) | 0.5 | Not endogenously expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34Cys) | Missense | <0.01% | Reduced receptor activation in vitro |
| c.457G>A (p.Val153Met) | Missense | <0.01% | Altered ligand binding affinity |
| c.862C>T (p.Arg288*) | Nonsense | <0.01% | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutation p.Arg288* leads to premature termination and loss of receptor function.
Gain of Function (GOF)
No gain-of-function mutations reported in HTR6.
Dominant Negative (DN)
No dominant-negative mutations reported in HTR6.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • serotonin binding |
| • adenylate cyclase activation | • G protein-coupled serotonin receptor signaling pathway |
| • chemical synaptic transmission | • nervous system development |
Pathways
• Serotonergic synapse (KEGG: hsa04726)
• cAMP signaling pathway (KEGG: hsa04024)
• GPCR downstream signaling (Reactome: R-HSA-388396)
Protein Summary
The 5-HT6 receptor is a 440-amino acid protein with seven transmembrane domains typical of GPCRs. It couples primarily to Gs, leading to cAMP production. The receptor is N-glycosylated and contains conserved cysteine residues for disulfide bond formation. It is expressed predominantly in the CNS and modulates cholinergic and glutamatergic neurotransmission. Structural studies reveal a binding pocket for serotonin and synthetic ligands, making it a target for drug development in cognitive disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HTR6 Knockout HEK293 Cell Line | EDJ-KQ1559 | Human | 3362 | Details Get a Quote |
| HTR6 Knockout HeLa Cell Line | EDJ-KQ53597 | Human | 3362 | Details Get a Quote |
| HTR6 Knockout A-549 Cell Line | EDJ-KQ62063 | Human | 3362 | Details Get a Quote |
| HTR6 Knockout HCT 116 Cell Line | EDJ-KQ70547 | Human | 3362 | Details Get a Quote |
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