C3AR1 (C3a Receptor 1): Complement Anaphylatoxin Receptor Gene
A key mediator of complement-driven inflammation, immune regulation, and tissue homeostasis, with emerging roles in cancer and neuroinflammation.
Gene Information Card
| Symbol | C3AR1 |
|---|---|
| Full Name | Complement C3a receptor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 12p13.31 |
| NCBI Gene ID | 719 ncbi.nlm.nih.gov/gene/719 |
| Ensembl ID | ENSG00000171860 |
| UniProt ID | Q16581 |
| OMIM ID | 605114 |
| HGNC ID | 1319 |
| Aliases | C3AR, AZ3B, C3aR, HNFAG09 |
Description
C3AR1 encodes the C3a receptor, a G-protein-coupled receptor (GPCR) that binds complement component C3a, a potent anaphylatoxin generated during complement activation. The receptor is expressed on various immune cells (e.g., mast cells, eosinophils, basophils, macrophages, neutrophils) and non-immune cells (e.g., endothelial cells, neurons). Activation of C3AR1 triggers intracellular signaling cascades (e.g., MAPK, PI3K/AKT) that regulate chemotaxis, degranulation, cytokine release, and cell survival. C3AR1 is implicated in inflammatory diseases, allergic responses, neuroinflammation, and cancer progression, making it a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Asthma | C3a-C3AR1 signaling promotes airway hyperresponsiveness and inflammation via mast cell and eosinophil activation. | Evidence from mouse models and human genetic association studies (e.g., PMID: 12374798). |
| Sepsis | C3AR1 activation contributes to systemic inflammatory response syndrome and organ damage. | Preclinical studies using C3ar1 knockout mice show reduced mortality (PMID: 18490740). |
| Cancer (e.g., breast, ovarian) | C3AR1 signaling in tumor microenvironment modulates immune evasion and tumor growth. | Expression profiling and functional studies (e.g., PMID: 27602760). |
| Neuroinflammation (e.g., Alzheimer's disease) | C3AR1 activation in microglia promotes neuroinflammation and neurodegeneration. | Elevated C3AR1 expression in AD brains; animal models (PMID: 29263200). |
| Rheumatoid arthritis | C3a-C3AR1 axis enhances inflammatory cytokine production in synovial tissue. | Clinical and experimental evidence (PMID: 15113986). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 12.3 | Medium |
| Spleen | 8.7 | Medium |
| Lung | 5.2 | Low |
| Liver | 2.1 | Low |
| Brain | 1.4 | Low |
| Kidney | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.6 | High expression; used as model for macrophage differentiation. |
| Jurkat (T cell) | 2.3 | Low expression; may be induced upon activation. |
| HeLa (cervical cancer) | 1.1 | Low expression; not a primary model. |
| A549 (lung cancer) | 4.5 | Moderate expression; relevant to lung inflammation studies. |
| HUVEC (endothelial) | 3.2 | Expression in endothelial cells; involved in vascular inflammation. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.104C>T (p.Thr35Met) | Missense | Rare (MAF <0.01) | Potential impact on receptor signaling; not well characterized. |
| c.457G>A (p.Val153Ile) | Missense | Rare | No known functional effect; likely benign. |
| c.733A>G (p.Ile245Val) | Missense | Rare | No clinical significance reported. |
| c.1000C>T (p.Arg334Cys) | Missense | Rare | May affect ligand binding; functional studies needed. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in C3AR1 are rare and not well documented. Complete knockout in mice leads to altered immune responses but is not lethal.
Gain of Function (GOF)
No gain-of-function mutations have been reported. Constitutive activation may occur via overexpression or aberrant signaling in disease contexts.
Dominant Negative (DN)
No dominant-negative mutations have been described for C3AR1.
View complete mutation data：
Gene Ontology (GO)
| • G-protein coupled receptor activity | • C3a anaphylatoxin receptor activity |
| • complement component C3a binding | • signal transduction |
| • cell surface receptor signaling pathway | • inflammatory response |
| • chemotaxis | • positive regulation of cytokine production |
| • plasma membrane |
Pathways
• Complement cascade (Reactome: R-HSA-166658)
• GPCR downstream signaling (Reactome: R-HSA-372790)
• Innate Immune System (Reactome: R-HSA-168249)
• MAPK signaling pathway (KEGG: hsa04010)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
Protein Summary
C3AR1 is a 482-amino acid, seven-transmembrane GPCR. It is synthesized as a precursor and cleaved into a mature form. The receptor is predominantly localized to the plasma membrane. Upon C3a binding, it undergoes conformational changes that activate heterotrimeric G proteins (Gαi/o), leading to inhibition of adenylate cyclase, activation of MAPK and PI3K pathways, and calcium mobilization. C3AR1 is expressed on myeloid cells and contributes to immune cell recruitment and activation. Its role in cancer is context-dependent, with both pro- and anti-tumorigenic effects reported.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| C3AR1 Knockout HEK293 Cell Line | EDJ-KQ4159 | Human | 719 | Details Get a Quote |
| C3AR1 Knockout HeLa Cell Line | EDJ-KQ52744 | Human | 719 | Details Get a Quote |
| C3AR1 Knockout A-549 Cell Line | EDJ-KQ61216 | Human | 719 | Details Get a Quote |
| C3AR1 Knockout HCT 116 Cell Line | EDJ-KQ69709 | Human | 719 | Details Get a Quote |
