FFAR1: Free Fatty Acid Receptor 1
A G-protein coupled receptor for medium- and long-chain fatty acids, key in metabolic signaling and potential therapeutic target for type 2 diabetes.
Gene Information Card
| Symbol | FFAR1 |
|---|---|
| Full Name | Free Fatty Acid Receptor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 2864 ncbi.nlm.nih.gov/gene/2864 |
| Ensembl ID | ENSG00000126267 |
| UniProt ID | O14842 |
| OMIM ID | 603820 |
| HGNC ID | 3698 |
| Aliases | GPR40, FFA1R, GPCR40 |
Description
FFAR1 (Free Fatty Acid Receptor 1), also known as GPR40, is a G-protein coupled receptor that binds medium- and long-chain free fatty acids. It is highly expressed in pancreatic beta cells and enteroendocrine cells, where it potentiates glucose-stimulated insulin secretion and incretin hormone release. FFAR1 is a key sensor of dietary fat and a therapeutic target for type 2 diabetes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | FFAR1 activation enhances insulin secretion; loss-of-function variants may impair beta-cell response to fatty acids. | ClinVar, NCBI |
| Impaired Glucose Tolerance | Reduced FFAR1 signaling linked to decreased incretin effect. | OMIM, PubMed |
| Obesity | FFAR1 mediates fatty acid-induced inflammation in adipose tissue; variants associated with metabolic syndrome. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.5 | High |
| Small Intestine | 8.3 | Medium |
| Brain | 2.1 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MIN6 (mouse beta-cell) | 15.2 | Model for insulin secretion studies |
| INS-1 (rat beta-cell) | 11.8 | Commonly used for FFAR1 signaling |
| HEK293 | 0.3 | Low endogenous expression; used for overexpression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg211His | Missense | <0.01% | Reduced receptor activity; associated with impaired insulin secretion |
| p.Val225Ala | Missense | <0.01% | Altered ligand binding; uncertain significance |
| p.Gly180Ser | Missense | <0.01% | Loss of function; reported in type 2 diabetes cohorts |
Mutation functional classification
Loss of Function (LOF)
p.Arg211His and p.Gly180Ser reduce FFAR1-mediated calcium signaling and insulin secretion.
Gain of Function (GOF)
No confirmed gain-of-function variants reported in ClinVar or COSMIC.
Dominant Negative (DN)
Not described for FFAR1.
View complete mutation data：
Gene Ontology (GO)
| • G-protein coupled receptor activity | • free fatty acid binding |
| • fatty acid receptor activity | • positive regulation of insulin secretion |
| • positive regulation of cytosolic calcium ion concentration | • glucose homeostasis |
Pathways
• GPCR downstream signaling (Gq/11 family)
• Fatty acid metabolism
• Insulin secretion pathway
Protein Summary
FFAR1 is a 300-amino acid G-protein coupled receptor with seven transmembrane domains. It is activated by medium- and long-chain free fatty acids (e.g., oleate, linoleate). Upon activation, it couples primarily to Gq/11 proteins, leading to phospholipase C activation, intracellular calcium release, and potentiation of glucose-stimulated insulin secretion from pancreatic beta cells. FFAR1 also promotes GLP-1 secretion from intestinal L-cells. It is a validated drug target for type 2 diabetes, with several synthetic agonists in clinical development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FFAR1 Knockout HEK293 Cell Line | EDJ-KQ2308 | Human | 2864 | Details Get a Quote |
| FFAR1 Knockout HeLa Cell Line | EDJ-KQ53411 | Human | 2864 | Details Get a Quote |
| FFAR1 Knockout A-549 Cell Line | EDJ-KQ61888 | Human | 2864 | Details Get a Quote |
| FFAR1 Knockout HCT 116 Cell Line | EDJ-KQ70367 | Human | 2864 | Details Get a Quote |
