C3AR1 Gene
Overview
Pathway Diagram
flowchart TD
A["C3AR1 Receptor"] -->|"associates with"| B["Complement System"]
A -->|"expressed in"| C["Microglia"]
A -->|"expressed in"| D["Macrophage"]
B -->|"activates"| E["C3a Signaling"]
E -->|"promotes"| F["Microglial Recruitment"]
F -->|"regulates"| G["M2 Polarization"]
A -->|"associated with"| H["NF-KB Pathway"]
H -->|"promotes"| I["Neuroinflammation"]
A -->|"regulates"| J["Blood-CSF Barrier"]
I -->|"leads to"| K["Motor Impairment"]
I -->|"contributes to"| L["Neurodegeneration"]
A -->|"regulates"| M["Dementia"]
L -->|"results in"| N["Cognitive Decline"]
classDef central fill:#006494,color:#e0e0e0
classDef protective fill:#1b5e20,color:#e0e0e0
classDef pathological fill:#ef5350,color:#0d0d1a
classDef regulatory fill:#4a1a6b,color:#e0e0e0
classDef outcomes fill:#5d4400,color:#e0e0e0
class A central
class G,J protective
class I,K,L,M pathological
class B,E,F,H regulatory
class N outcomes
...C3AR1 Gene
Overview
Pathway Diagram
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">C3AR1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>C3AR1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Complement C3a Receptor 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5p13.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[719](https://www.ncbi.nlm.nih.gov/gene/719)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>[ENSG00000171860](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000171860)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q16581](https://www.uniprot.org/uniprot/Q16581)</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>C3a anaphylatoxin chemotactic receptor</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">73 edges</a></td>
</tr>
</table>
C3AR1 (Complement C3a Receptor 1) encodes the C3a anaphylatoxin chemotactic receptor, a G protein-coupled receptor (GPCR) that mediates the biological effects of complement component C3a. In the central nervous system, C3AR1 is expressed on [microglia](/cell-types/microglia-neuroinflammation), [astrocytes](/entities/astrocytes), and [neurons](/entities/neurons), where it plays critical roles in neuroinflammation, synaptic pruning, and response to neurodegenerative pathology["@kemper2018"].
The [complement system](/entities/complement-system), particularly the C3a-C3aR axis, has emerged as a key mediator of neuroinflammation in Alzheimer's disease, [Parkinson's disease](/diseases/parkinsons-disease), and other neurodegenerative conditions. C3aR signaling can promote both protective and deleterious effects depending on disease stage and cellular context["@morgan2015"].
Function
C3AR1 encodes a seven-transmembrane G protein-coupled receptor that specifically binds the complement activation fragment C3a. Upon C3a binding, the receptor couples primarily to Gαi and Gαq proteins, leading to[@coulthard2015]:
Intracellular calcium mobilization through phospholipase C activation
Chemotactic responses in immune cells
Cytokine and chemokine secretion from myeloid cells
[Reactive oxygen species](/entities/reactive-oxygen-species) production
Enhanced phagocytic activityIn the CNS, C3aR signaling influences[@rahpeymai2021]:
- Microglial activation states and cytokine production
- Astrocyte reactivity and scar formation
- [Blood-brain barrier](/entities/blood-brain-barrier) permeability
- Synaptic plasticity and pruning
Expression
C3AR1 is expressed across multiple cell types:
Peripheral Expression
- Neutrophils: Primary site of expression; mediates chemotaxis
- Monocytes/macrophages: Regulates inflammatory responses
- Mast cells: Mediates degranulation and cytokine release
- Eosinophils: Promotes chemotaxis and activation
CNS Expression[@luo2020]
- Microglia: Constitutively expressed; upregulated during neuroinflammation
- Astrocytes: Induced under inflammatory conditions
- Neurons: Low basal expression; upregulated in disease states
- Endothelial cells: Contributes to BBB permeability changes
Disease Associations
Alzheimer's Disease
The C3a-C3aR axis contributes to Alzheimer's pathology through multiple mechanisms[@lian2016]:
Synaptic pruning dysregulation: C3aR mediates excessive microglial synaptic elimination in AD
Neuroinflammation amplification: C3aR signaling promotes pro-inflammatory cytokine release
[Aβ](/proteins/amyloid-beta) plaque interaction: Complement activation occurs at amyloid deposits
Cognitive impairment: C3aR-deficient mice show protection against cognitive decline in AD modelsGWAS studies have identified associations between C3AR1 polymorphisms and AD risk, particularly in variants affecting receptor expression levels[@crehan2012].
Parkinson's Disease
In Parkinson's disease, C3aR signaling contributes to[@wang2020]:
- Microglial activation in the substantia nigra
- Dopaminergic neuron vulnerability
- [α-synuclein](/proteins/alpha-synuclein)-induced neuroinflammation
- Progressive neurodegeneration
C3aR antagonism in PD models reduces neuroinflammation and provides partial neuroprotection.
Multiple Sclerosis
C3aR plays a dual role in MS[@van2019]:
- Pro-inflammatory: Promotes Th17 responses and CNS inflammation
- Repair-promoting: May support remyelination in certain contexts
Stroke and Brain Injury
Following ischemic stroke, C3aR activation[@ahmad2019]:
- Increases BBB permeability
- Promotes edema formation
- Attracts peripheral immune cells
- Influences long-term tissue remodeling
Key Publications
[Bohnack et al., C3a receptor signaling in inflammation (2021)](https://pubmed.ncbi.nlm.nih.gov/33638156/)
[Wyss-Coray et al., Complement and microglia in neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/30814206/)
[Lian et al., C3aR in synaptic pruning and Alzheimer's (2016)](https://pubmed.ncbi.nlm.nih.gov/27595286/)
[Schafer et al., Microglia sculpt neural circuits (2012)](https://pubmed.ncbi.nlm.nih.gov/22875485/)
[Stevens et al., Complement cascade mediates CNS synapse elimination (2007)](https://pubmed.ncbi.nlm.nih.gov/17643333/)Therapeutic Targeting
C3aR Antagonists
Several C3aR antagonists have been developed for inflammatory conditions[@woodruff2015]:
SB 290157: First-generation antagonist; has partial agonist activity
CJ4a and analogs: Improved selectivity
IC3aR-01: Novel small molecule antagonist
DF2593A: Investigated for inflammatory painClinical Relevance
C3aR targeting is being explored for[@mastorakos2021]:
- Neuroinflammatory diseases
- Age-related cognitive decline
- Traumatic brain injury
- Multiple sclerosis
Interactions
C3aR interacts with:
- C3a: Primary ligand (anaphylatoxin)
- Gαi/Gαq proteins: Signal transduction
- β-arrestin: Receptor desensitization
- Other complement receptors: [C5aR1](/genes/c5ar1), C5aR2 (functional crosstalk)
Related Pages
- [Complement System](/mechanisms/complement-system-neurodegeneration)
- [Microglia](/cell-types/microglia)
- [Neuroinflammation](/mechanisms/neuroinflammation)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [C5AR1](/genes/c5ar1)
See Also
- [C3AR1 Protein](/proteins/amyloid-beta)
- [Complement System](/mechanisms/complement-system-neurodegeneration)
- [Neuroinflammation](/mechanisms/neuroinflammation)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
External Links
- [NCBI Gene: C3AR1](https://www.ncbi.nlm.nih.gov/gene/719)
- [Ensembl: ENSG00000171860](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000171860)
- [UniProt: Q16581](https://www.uniprot.org/uniprot/Q16581)
- [GeneCards: C3AR1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=C3AR1)
- [OMIM: C3AR1](https://omim.org/search?search=C3AR1)
- [Allen Brain Atlas: C3AR1](https://human.brain-map.org/microarray/search/show?search_term=C3AR1)
References
[Unknown, Kemper C, Kohl J. Novel functions of complement in T cell regulation. Semin Immunol. 2018;37:23-32 (2018)](https://pubmed.ncbi.nlm.nih.gov/28587914/)
[Unknown, Morgan BP, Harris CL. Complement, a target for therapy in inflammatory and degenerative diseases. Nat Rev Drug Discov. 2015;14(12):857-77 (2015)](https://pubmed.ncbi.nlm.nih.gov/26429718/)
[Unknown, Coulthard LG, Woodruff TM. Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence. J Immunol. 2015;195(5):1979-86 (2015)](https://pubmed.ncbi.nlm.nih.gov/26109689/)
[Rahpeymai Y, et al., Gene expression profiling of complement receptors in brain. J Neuroinflammation. 2021;18(1):105 (2021)](https://pubmed.ncbi.nlm.nih.gov/33849517/)
[Luo C, et al., Complement receptor expression in glial cells. J Neuroinflammation. 2020;17(1):253 (2020)](https://pubmed.ncbi.nlm.nih.gov/32819345/)
[Lian H, et al., Astrocyte-microglia cross talk through complement activation. Neuron. 2016;90(4):827-41 (2016)](https://pubmed.ncbi.nlm.nih.gov/27595286/)
[Crehan H, et al., Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology. 2012;217(2):244-51 (2012)](https://pubmed.ncbi.nlm.nih.gov/22078311/)
[Wang Y, et al., C3aR deficiency attenuates neuroinflammation in Parkinson's disease models. Neurobiol Dis. 2020;145:105098 (2020)](https://pubmed.ncbi.nlm.nih.gov/32911078/)
[van der Poel M, et al., Transcriptional profiling of human microglia reveals grey-white matter heterogeneity. Nat Neurosci. 2019;22(1):68-78 (2019)](https://pubmed.ncbi.nlm.nih.gov/30559448/)
[Ahmad S, et al., Complement C3a receptor in stroke. Stroke. 2019;50(7):1819-1826 (2019)](https://pubmed.ncbi.nlm.nih.gov/31107147/)
[Woodruff TM, et al., C3a receptor antagonists: past, present and future. Mol Immunol. 2015;68(2):539-48 (2015)](https://pubmed.ncbi.nlm.nih.gov/26253831/)
[Unknown, Mastorakos P, McGavern D. The complement system in neurological diseases. Trends Immunol. 2021;42(9):752-770 (2021)](https://pubmed.ncbi.nlm.nih.gov/34314834/)Pathway Diagram
The following diagram shows the key molecular relationships involving C3AR1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)