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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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HTR1F
5-hydroxytryptamine receptor 1F
Chromosome 3 · 3p11.2-p11.1
NCBI Gene: 3355Ensembl: ENSG00000179097.8HGNC: HGNC:5292UniProt: P30939
27PubMed Papers
20Diseases
11Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
Gi/o-coupled serotonin receptor activityG protein-coupled serotonin receptor activityprotein bindingserotonin bindingmigraine disorderschizophreniapost operative nausea and vomitingmajor depressive disorder
✦AI Summary

HTR1F encodes a G-protein coupled receptor for serotonin (5-hydroxytryptamine) that mediates inhibitory neurotransmission 1. The receptor is coupled to G(i)/G(o) alpha proteins and suppresses adenylate cyclase activity upon ligand binding 1. HTR1F also functions as a receptor for lasmiditan, a clinically approved migraine therapeutic 1, and exhibits high conservation across vertebrate species 2. Beyond canonical serotonin signaling, HTR1F activation stimulates MAPK/ERK signaling cascades 2. Genetically, HTR1F variants contribute to migraine susceptibility as identified in a genome-wide association study of 102,084 cases, representing a novel migraine-specific drug target 3. HTR1F is also genetically associated with sleep apnea risk in non-obese individuals, with expression predominantly in neurons 4. Additionally, HTR1F expression correlates with ACTH release and potentially modulates pain-itch sensory processing in dorsal root ganglion neurons 56. Recent cancer research indicates HTR1F upregulation in 17 cancer types associates with poor prognosis and immune microenvironment alterations, particularly in lung squamous cell carcinoma 7. These findings establish HTR1F as a multifunctional receptor with relevance across neurological, sleep, and malignant disease contexts.

Sources cited
1
HTR1F is a G(i)/G(o)-coupled receptor for serotonin that inhibits adenylate cyclase and serves as a lasmiditan receptor for migraine treatment
PMID: 34239069
2
HTR1F is identified as a migraine-specific drug target in a genome-wide association study of 102,084 migraine cases
PMID: 35115687
3
HTR1F is genetically associated with sleep apnea risk in non-obese individuals, with expression primarily in neurons
PMID: 40571323
4
HTR1F is functionally conserved across vertebrates and activates MAPK/ERK signaling cascades when bound to serotonin agonists
PMID: 34207786
5
HTR1F is a G protein-coupled receptor associated with ACTH release in mammals
PMID: 32292413
6
HTR1F is expressed in dorsal root ganglion pruriceptor neurons involved in itch sensation
PMID: 33693534
7
HTR1F is upregulated in 17 cancer types and associated with poor prognosis, immune modulation, and drug sensitivity in multiple cancers
PMID: 41007799
Disease Associationsⓘ20
migraine disorderOpen Targets
0.60Moderate
schizophreniaOpen Targets
0.59Moderate
post operative nausea and vomitingOpen Targets
0.48Moderate
major depressive disorderOpen Targets
0.47Moderate
obesityOpen Targets
0.46Moderate
psychosisOpen Targets
0.37Weak
depressive disorderOpen Targets
0.37Weak
Nausea and vomitingOpen Targets
0.37Weak
prostate carcinomaOpen Targets
0.33Weak
intestinal diseaseOpen Targets
0.32Weak
gastric ulcerOpen Targets
0.26Weak
hemorrhageOpen Targets
0.26Weak
migraine with auraOpen Targets
0.26Weak
migraine without auraOpen Targets
0.26Weak
ovarian neoplasmOpen Targets
0.25Weak
carbuncleOpen Targets
0.25Weak
FuruncleOpen Targets
0.25Weak
insomniaOpen Targets
0.22Weak
diabetes mellitusOpen Targets
0.21Weak
Abnormality of the skeletal systemOpen Targets
0.21Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets11
ALMOTRIPTANApproved
Serotonin 1b (5-HT1b) receptor agonist
migraine disorder
ALMOTRIPTAN MALATEApproved
Serotonin 1b (5-HT1b) receptor agonist
migraine disorder
AMISULPRIDEApproved
Serotonin (5-HT) receptor antagonist
Nausea and vomiting
DEXFENFLURAMINEApproved
Serotonin (5-HT) receptor agonist
obesity
DEXFENFLURAMINE HYDROCHLORIDEUNKNOWN
Serotonin (5-HT) receptor agonist
ELETRIPTANApproved
Serotonin 1b (5-HT1b) receptor agonist
migraine disorder
ELETRIPTAN HYDROBROMIDEApproved
Serotonin 1b (5-HT1b) receptor agonist
migraine disorder
LASMIDITANApproved
Serotonin 1f (5-HT1f) receptor agonist
migraine disorder
LASMIDITAN SUCCINATEApproved
Serotonin 1f (5-HT1f) receptor agonist
migraine disorder
ZIMELDINEApproved
Serotonin (5-HT) receptor antagonist
major depressive disorder
ZIMELDINE HYDROCHLORIDEUNKNOWN
Serotonin (5-HT) receptor antagonist
Related Genes
GNG4Protein interaction100%GNGT2Protein interaction100%GNG2Protein interaction100%GNG7Protein interaction100%GNG12Protein interaction100%NPYProtein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
36%
Heart
16%
Lung
15%
Ovary
9%
Liver
0%
Gene Interaction Network
Click a node to explore
HTR1FGNG4GNGT2GNG2GNG7GNG12NPY
PROTEIN STRUCTURE
Preparing viewer…
PDB7EXD · 3.40 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.01LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.67 [0.46–1.01]
RankingsWhere HTR1F stands among ~20K protein-coding genes
  • #12,580of 20,598
    Most Researched27
  • #180of 1,025
    FDA-Approved Drug Targets9 · top quartile
  • #9,848of 17,882
    Most Constrained (LOEUF)1.01
Genes detectedHTR1F
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles.
PMID: 35115687
Nat Genet · 2022
1.00
2
Assignment of the human serotonin 1F receptor gene (HTR1F) to the short arm of chromosome 3 (3p13-p14.1).
PMID: 9394293
Mol Membr Biol · 1997
0.90
3
Genetic associations between serotonin receptor 1F (
PMID: 40571323
Eur Respir J · 2025
0.80
4
Molecular Cloning and Functional Characterization of Three 5-HT Receptor Genes (
PMID: 34207786
Genes (Basel) · 2021
0.70
5
The discovery, structure, and function of 5-HTR1E serotonin receptor.
PMID: 37723479
Cell Commun Signal · 2023
0.60