HCAR1: Hydroxycarboxylic Acid Receptor 1
A G-protein-coupled receptor for lactate and its role in metabolism, neuroprotection, and cancer.
Gene Information Card
| Symbol | HCAR1 |
|---|---|
| Full Name | Hydroxycarboxylic Acid Receptor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 27198 ncbi.nlm.nih.gov/gene/27198 |
| Ensembl ID | ENSG00000196917 |
| UniProt ID | Q9BXC0 |
| OMIM ID | 606669 |
| HGNC ID | 4532 |
| Aliases | GPR81, FKSG80, HCA1, LACR1 |
Description
HCAR1 encodes a G-protein-coupled receptor that is activated by lactate (L-lactic acid) and other hydroxycarboxylic acids. It is involved in metabolic regulation, particularly in adipose tissue where it inhibits lipolysis, and in the brain where it mediates neuroprotective effects. HCAR1 also plays a role in cancer cell metabolism and immune modulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | HCAR1 activation in adipocytes inhibits lipolysis via Gi/o signaling, reducing free fatty acid release. | PMID: 19029989 |
| Ischemic Stroke | Lactate-mediated HCAR1 activation in neurons reduces excitotoxicity and apoptosis. | PMID: 24813611 |
| Colorectal Cancer | HCAR1 overexpression in tumor cells promotes lactate uptake and metabolic adaptation. | PMID: 28753428 |
| Breast Cancer | HCAR1 expression correlates with poor prognosis and lactate-driven angiogenesis. | PMID: 30389936 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Brain (cortex) | 8.3 | Low |
| Liver | 3.1 | Not detected |
| Skeletal muscle | 2.7 | Not detected |
| Kidney | 1.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Overexpressed in recombinant systems |
| MCF7 (breast cancer) | 9.8 | Endogenous expression |
| HCT116 (colorectal) | 7.4 | Endogenous expression |
| SH-SY5Y (neuroblastoma) | 6.1 | Endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Reduced receptor activity in vitro |
| c.454G>A (p.Gly152Ser) | Missense | <0.01% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
p.Thr34Met reduces lactate-induced signaling.
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 | • hydroxycarboxylic acid binding |
| • lactate binding | • negative regulation of adenylate cyclase activity |
| • negative regulation of lipolysis | • response to lactate |
Pathways
• GPCR downstream signaling (Gi/o)
• Lactate signaling in adipocytes
• Neuroprotection via lactate
Protein Summary
HCAR1 (GPR81) is a 346-amino acid transmembrane receptor that couples to Gi/o proteins. Upon lactate binding, it inhibits adenylyl cyclase, reducing cAMP levels. It is highly expressed in adipose tissue and brain, and its activation modulates energy metabolism, neuronal survival, and tumor growth.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HCAR1 Knockout HEK293 Cell Line | EDJ-KQ1793 | Human | 27198 | Details Get a Quote |
| HCAR1 Knockout HeLa Cell Line | EDJ-KQ56031 | Human | 27198 | Details Get a Quote |
| HCAR1 Knockout A-549 Cell Line | EDJ-KQ64517 | Human | 27198 | Details Get a Quote |
| HCAR1 Knockout HCT 116 Cell Line | EDJ-KQ72975 | Human | 27198 | Details Get a Quote |
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