HCAR2 (Hydroxycarboxylic Acid Receptor 2)
G protein-coupled receptor for niacin and ketone bodies; role in lipid metabolism and inflammation
Gene Information Card
| Symbol | HCAR2 |
|---|---|
| Full Name | Hydroxycarboxylic Acid Receptor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 338442 ncbi.nlm.nih.gov/gene/338442 |
| Ensembl ID | ENSG00000182782 |
| UniProt ID | Q8TDS4 |
| OMIM ID | 606039 |
| HGNC ID | 16827 |
| Aliases | GPR109A, HM74A, NIACR1, PUMAG |
Description
HCAR2 encodes a G protein-coupled receptor that is activated by nicotinic acid (niacin) and beta-hydroxybutyrate. It is primarily expressed in adipocytes and immune cells, mediating anti-lipolytic effects and anti-inflammatory responses. The receptor couples to Gi-type G proteins, inhibiting adenylyl cyclase and reducing cAMP levels. HCAR2 is a target for dyslipidemia treatment and has been implicated in neuroinflammation and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dyslipidemia | HCAR2 activation reduces free fatty acid release from adipose tissue via Gi signaling | PMID: 12711604 |
| Atherosclerosis | Anti-inflammatory effects via HCAR2 on macrophages reduce plaque formation | PMID: 20023630 |
| Type 2 Diabetes | Altered HCAR2 expression in adipose tissue linked to insulin resistance | PMID: 21518867 |
| Neuroinflammation | Beta-hydroxybutyrate activation of HCAR2 on microglia suppresses inflammation | PMID: 25706243 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Spleen | 8.3 | Low |
| Bone marrow | 6.1 | Low |
| Lung | 4.7 | Low |
| Liver | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Adipocytes | 15.2 | Primary adipocytes |
| Macrophages | 9.8 | Differentiated THP-1 cells |
| Microglia | 7.4 | Human microglial cell line |
| HepG2 | 1.3 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs61733438 (p.Arg102Cys) | missense | 0.2% in European populations | Reduced receptor activity in vitro |
| rs61733439 (p.Leu215Phe) | missense | 0.1% in East Asian populations | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
rs61733438 (p.Arg102Cys) shows reduced cAMP inhibition in cellular assays
Gain of Function (GOF)
No confirmed gain-of-function mutations reported
Dominant Negative (DN)
Not described
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • nicotinic acid receptor activity |
| • hydroxycarboxylic acid binding | • adenylate cyclase inhibition |
| • negative regulation of lipolysis | • inflammatory response |
Pathways
• Niacin metabolism
• GPCR downstream signaling (Gi)
• cAMP signaling pathway
• Ketone body metabolism
Protein Summary
HCAR2 is a 363-amino acid transmembrane protein with seven alpha-helical domains typical of GPCRs. It binds niacin and beta-hydroxybutyrate, leading to Gi-mediated inhibition of adenylyl cyclase. The receptor is expressed on adipocytes, macrophages, and microglia, where it regulates lipid mobilization and inflammation. Structural studies indicate a conserved ligand-binding pocket critical for drug design.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HCAR2 Knockout HEK293 Cell Line | EDJ-KQ1794 | Human | 338442 | Details Get a Quote |
| HCAR2 Knockout HeLa Cell Line | EDJ-KQ59612 | Human | 338442 | Details Get a Quote |
| HCAR2 Knockout A-549 Cell Line | EDJ-KQ68077 | Human | 338442 | Details Get a Quote |
| HCAR2 Knockout HCT 116 Cell Line | EDJ-KQ76453 | Human | 338442 | Details Get a Quote |
