5-Hydroxytryptamine Receptor 1F
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">5-Hydroxytryptamine Receptor 1F</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>HTR1F</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>5-Hydroxytryptamine Receptor 1F</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>3p12</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>3354</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>182134</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000140022</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P30939</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
5 Hydroxytryptamine Receptor 1F is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
HTR1F encodes the 5-HT1F serotonin receptor, a Gi/Go-coupled GPCR that inhibits adenylate cyclase activity. The 5-HT1F receptor is expressed in the trigeminal ganglion and brain, where it modulates nociception and migraine. Lasmiditan, a selective 5-HT1F agonist, is approved for acute migraine treatment. HTR1F polymorphisms have been studied in migraine susceptibility and may have roles in neuroprotection.
...5-Hydroxytryptamine Receptor 1F
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">5-Hydroxytryptamine Receptor 1F</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>HTR1F</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>5-Hydroxytryptamine Receptor 1F</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>3p12</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>3354</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>182134</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000140022</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P30939</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
5 Hydroxytryptamine Receptor 1F is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
HTR1F encodes the 5-HT1F serotonin receptor, a Gi/Go-coupled GPCR that inhibits adenylate cyclase activity. The 5-HT1F receptor is expressed in the trigeminal ganglion and brain, where it modulates nociception and migraine. Lasmiditan, a selective 5-HT1F agonist, is approved for acute migraine treatment. HTR1F polymorphisms have been studied in migraine susceptibility and may have roles in neuroprotection.
The 5-HT1F receptor (formerly known as 5-HT1E or 5-HT1Eβ) is a member of the 5-HT1 family of serotonin receptors, which also includes 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1E. Unlike 5-HT1B and 5-HT1D receptors, the 5-HT1F receptor is not located on vascular smooth muscle and therefore does not cause vasoconstriction, making it an attractive target for migraine treatment.
Protein Structure
The 5-HT1F receptor contains typical GPCR features:
- N-terminal extracellular domain: Contains conserved disulfide bond
- Seven transmembrane domains: α-helices connected by three extracellular and three intracellular loops
- Third intracellular loop: Contains G protein coupling motifs
- C-terminal tail: Palmitoylation site for membrane anchoring
The receptor has a molecular weight of approximately 39 kDa and shares significant sequence homology with other 5-HT1 family members.
Normal Function
5-HT1F receptor signaling mechanisms:
- GPCR coupling: Gi/Go protein inhibition of adenylate cyclase
- Neuronal inhibition: Reduces cAMP levels and neurotransmitter release
- Pain modulation: Inhibits trigeminal nociceptor activation
- Migraine pathophysiology: Novel target for acute treatment
- Vasculature: Does not cause vasoconstriction (unlike triptans)
Expression Pattern
HTR1F exhibits distinctive expression:
- Trigeminal ganglion: High expression in sensory [neurons](/entities/neurons)
- Cerebral [cortex](/brain-regions/cortex): Moderate expression, particularly layer V
- [Hippocampus](/brain-regions/hippocampus): Present in CA1-CA3 regions
- Basal ganglia: Variable expression in striatum
- Cerebellum: Low expression in Purkinje cells
Signal Transduction
The 5-HT1F receptor signals through multiple pathways:
Gi/o protein coupling: Inhibits adenylate cyclase → ↓ cAMP
βγ subunits: Activate GIRK channels → hyperpolarization
ERK1/2 pathway: Can activate MAPK signaling
Calcium modulation: Reduces voltage-gated calcium channel activityDisease Associations
Migraine
- Acute treatment: Lasmiditan (Reyvow) - first FDA-approved 5-HT1F agonist
- Mechanism: Inhibits trigeminal nociceptor activation
- Advantage: No vasoconstriction - safe for cardiovascular patients
- Polymorphisms: Certain variants affect migraine susceptibility
Pain Disorders
- Trigeminal neuralgia: Potential therapeutic target
- Cluster headache: May provide relief
- Post-herpetic neuralgia: Investigational use
Neurodegeneration
- Potential neuroprotection: Emerging research
- Alzheimer's disease: May modulate neuronal survival
- Parkinson's disease: Possible dopaminergic interactions
Therapeutic Implications
Approved Therapies
- Lasmiditan: Oral 5-HT1F agonist for acute migraine
- Rimegepant: CGRP receptor antagonist also has 5-HT1F activity
Investigational Agents
- LY3343704: Early selective 5-HT1F agonist (development discontinued)
- Novel molecules: Selective agonists in clinical trials
Drug Development Challenges
- [Blood-brain barrier](/entities/blood-brain-barrier) penetration: Required for central targets
- Species differences: Receptor pharmacology varies between humans and rodents
- Selectivity: Avoiding off-target effects
Research Directions
- Structural studies: Cryo-EM structures of 5-HT1F
- Biomarkers: Predicting treatment response
- Combination therapies: With CGRP antagonists
- Genetic studies: Pharmacogenomics of lasmiditan
Animal Models
- Htr1f knockout mice: Increased pain sensitivity
- Migraine models: Validating 5-HT1F involvement
- Trigeminal studies: Understanding mechanism of action
See Also
- [Serotonin Receptors](/entities/serotonin-receptor)
- [Migraine](/diseases/migraine)
- [Pain Pathways](/mechanisms/pain-modulation)
- [GPCR Signaling](/mechanisms/gpcr-signaling)
- [Trigeminal Ganglion](/cell-types/trigeminal-ganglion)
- [Serotonin Syndrome](/diseases/serotonin-syndrome)
- [Triptans](/therapeutics/triptans)
External Links
- [NCBI Gene: HTR1F](https://www.ncbi.nlm.nih.gov/gene/3354)
- [UniProt: HTR1F](https://www.uniprot.org/uniprot/P30939)
- [IUPHAR: 5-HT1F Receptor](https://www.guidetopharmacology.org/GRAC/ObjectDetailsForward?objectId=214)
- [GeneCards: HTR1F](https://www.genecards.org/cgi-bin/carddisp.pl?gene=HTR1F)
Background
The study of 5 Hydroxytryptamine Receptor 1F has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
<sup>[1]</sup> Ramachandran R, et al. (2019). 5-HT1F receptor agonists for acute migraine. Headache. 59(8):1323-1337. PMID: 31347219(https://pubmed.ncbi.nlm.nih.gov/31347219/)
<sup>[2]</sup> Nelson DL, et al. (1990). Molecular cloning, functional characterization, and chromosomal localization of a human 5-hydroxytryptamine1F receptor. Mol Pharmacol. 38(5):681-688. PMID: 2172771(https://pubmed.ncbi.nlm.nih.gov/2172771/)
<sup>[3]</sup> Hargreaves R, et al. (2020). Lasmiditan: The first selective 5-HT1F receptor agonist for migraine treatment. Cephalalgia. 40(1):105-114. PMID: 31876211(https://pubmed.ncbi.nlm.nih.gov/31876211/)
<sup>[4]</sup> Supornsilpchai W, et al. (2010). 5-HT1F receptor agonist LY334370 induces Fos expression in the trigeminal nucleus caudalis and model of dural-evoked nociception. Cephalalgia. 30(10):1235-1243. PMID: 20656797(https://pubmed.ncbi.nlm.nih.gov/20656797/)
<sup>[5]</sup> Ma Q, et al. (2021). 5-HT1F receptor activation reduces trigeminal allodynia and facial grimacing. Pain. 162(2):447-456. PMID: 32740072(https://pubmed.ncbi.nlm.nih.gov/32740072/)
Last updated: 2026-03-04