C5AR1 Gene
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">C5AR1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>C5AR1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Complement C5a Receptor 1</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>CD88, C5AR, C5A</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.33</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[728](https://www.ncbi.nlm.nih.gov/gene/728)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>[ENSG00000131831](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000131831)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P21730](https://www.uniprot.org/uniprot/P21730)</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>C5a anaphylatoxin chemotactic receptor</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Avacopan</td>
<td>FDA-approved</td>
</tr>
<tr>
<td class="label">PMX53</td>
<td>Phase II completed</td>
</tr>
<tr>
<td class="label">DF2593A</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">NMe-OPHA</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><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/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/lupus" style="color:#ef9a9a">Lupus</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">52 edges</a></td>
</tr>
</table>
C5AR1 (Complement C5a Receptor 1), also known as CD88, encodes the C5a anaphylatoxin chemotactic receptor, a G protein-coupled receptor (GPCR) that mediates the biological effects of complement component C5a. C5AR1 is one of the most potent chemoattractant receptors in the immune system and plays critical roles in neuroinflammation and neurodegeneration["@manthey2009"].
In the central nervous system, C5AR1 is expressed on [microglia](/cell-types/microglia-neuroinflammation), [astrocytes](/entities/astrocytes), [neurons](/entities/neurons), and endothelial cells. The C5a-C5aR1 axis has emerged as a key mediator of neuroinflammatory responses in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative conditions["@van2019"].
Function
C5AR1 encodes a seven-transmembrane G protein-coupled receptor that specifically binds C5a, a 74-amino acid peptide generated during complement activation. C5a is one of the most potent inflammatory mediators, and C5aR1 mediates its effects through[@klos2013]:
Chemotaxis: Directs migration of immune cells toward sites of complement activation
Degranulation: Triggers release of histamine and other mediators from mast cells
Cytokine production: Induces TNF-α, IL-1β, IL-6, and other pro-inflammatory cytokines
Oxidative burst: Promotes [reactive oxygen species](/entities/reactive-oxygen-species) production in phagocytes
Cell survival/apoptosis regulation: Context-dependent effects on cell fateSignaling Mechanisms
C5aR1 couples to multiple G proteins[@cain2002]:
- Gαi: Inhibits adenylate cyclase, activates PI3K and MAPK pathways
- Gαq: Activates phospholipase C-β, increases intracellular calcium
- Gα12/13: Regulates cytoskeletal reorganization and cell migration
Expression
Peripheral Expression
- Neutrophils: Highest expression; mediates chemotaxis and activation
- Monocytes/macrophages: Regulates inflammatory responses
- Dendritic cells: Influences antigen presentation and T cell responses
- Mast cells: Mediates degranulation and cytokine release
- T cells: Modulates Th1/Th17 differentiation
CNS Expression[@huang2020]
- Microglia: Upregulated during neuroinflammation; key mediator of microglial activation
- Astrocytes: Induced by inflammatory stimuli
- Neurons: Expressed at low levels; may have neuroprotective or neurotoxic effects
- Endothelial cells: Regulates [BBB](/entities/blood-brain-barrier) permeability
- Oligodendrocytes: May contribute to demyelination
Disease Associations
Alzheimer's Disease
The C5a-C5aR1 axis contributes to AD pathogenesis through multiple mechanisms[@fonseca2017]:
Synaptic loss: C5aR1 on microglia promotes excessive synaptic pruning
Neuroinflammation: Amplifies inflammatory cascades in response to [Aβ](/proteins/amyloid-beta)
Neuronal toxicity: Direct and indirect neurotoxic effects
[Tau](/proteins/tau) pathology: May influence tau phosphorylation and spreadC5aR1-deficient [APP](/entities/app-protein)/PS1 mice show reduced pathology and improved cognition, supporting a pathogenic role[@sanchezmejia2009].
Parkinson's Disease
In Parkinson's disease, C5aR1 contributes to[@husmann2020]:
- Microglial activation in the substantia nigra
- [α-synuclein](/proteins/alpha-synuclein)-induced neuroinflammation
- Progressive loss of dopaminergic neurons
- Peripheral immune cell infiltration
C5aR1 antagonism provides neuroprotection in PD models.
Amyotrophic Lateral Sclerosis
C5aR1 expression is elevated in ALS[@woodruff2008]:
- Increased in spinal cord microglia
- Correlates with disease progression
- May contribute to motor neuron death
- Potential therapeutic target
Traumatic Brain Injury
Following TBI, C5aR1 signaling[@sewell2004]:
- Promotes acute neuroinflammation
- Increases BBB permeability
- Attracts peripheral immune cells
- Influences long-term neurodegeneration
Multiple Sclerosis
C5aR1 plays complex roles in MS[@michels2022]:
- Promotes CNS inflammation and demyelination
- May also have regulatory functions
- Target for therapeutic intervention
Therapeutic Targeting
C5aR1 Antagonists
Several C5aR1 antagonists are in development or clinical use[@kohl2018]:
Neurological Applications
C5aR1 antagonism is being explored for:
- Alzheimer's disease neuroinflammation
- Parkinson's disease neuroprotection
- ALS motor neuron protection
- Traumatic brain injury
- Stroke recovery
Genetic Variants
Polymorphisms in C5AR1 have been associated with:
- Increased susceptibility to inflammatory diseases
- Variable response to infection
- Possible AD risk modification (ongoing research)
Interactions
C5aR1 interacts with:
- C5a: Primary agonist (anaphylatoxin)
- C5a-desArg: Less potent agonist
- G proteins: Gαi, Gαq, Gα12/13
- β-arrestins: Receptor desensitization and internalization
- C5aR2 (C5L2): Related receptor; may modulate C5aR1 signaling
Related Pages
- [C3AR1](/genes/c3ar1)
- [Complement System](/mechanisms/complement-system-neurodegeneration)
- [Microglia](/cell-types/microglia)
- [Neuroinflammation](/mechanisms/neuroinflammation)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
Key Publications
[Monk et al., C5a receptor antagonists (2007)](https://pubmed.ncbi.nlm.nih.gov/17220826/)
[Woodruff et al., Complement in neurodegeneration (2011)](https://pubmed.ncbi.nlm.nih.gov/21697165/)
[Fonseca et al., C5aR1 in Alzheimer's disease (2017)](https://pubmed.ncbi.nlm.nih.gov/28481972/)
[Husmann et al., C5aR1 in Parkinson's disease (2020)](https://pubmed.ncbi.nlm.nih.gov/31887557/)See Also
- [C5AR1 Protein](/proteins/amyloid-beta)
- [Complement System](/mechanisms/complement-system-neurodegeneration)
- [Neuroinflammation](/mechanisms/neuroinflammation)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [NCBI Gene: C5AR1](https://www.ncbi.nlm.nih.gov/gene/728)
- [Ensembl: ENSG00000131831](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000131831)
- [UniProt: P21730](https://www.uniprot.org/uniprot/P21730)
- [GeneCards: C5AR1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=C5AR1)
- [OMIM: C5AR1](https://omim.org/search?search=C5AR1)
- [Allen Brain Atlas: C5AR1](https://human.brain-map.org/microarray/search/show?search_term=C5AR1)
References
[Manthey HD, et al., Complement C5a receptor in inflammation. J Mol Med. 2009;87(4):375-8 (2009)](https://pubmed.ncbi.nlm.nih.gov/19234647/)
[van der Poel M, et al., Transcriptional profiling of microglia. Nat Neurosci. 2019;22(1):68-78 (2019)](https://pubmed.ncbi.nlm.nih.gov/30559448/)
[Klos A, et al., The role of the anaphylatoxins in health and disease. Mol Immunol. 2013;56(3):159-66 (2013)](https://pubmed.ncbi.nlm.nih.gov/23953837/)
[Unknown, Cain SA, Monk PN. The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). J Biol Chem. 2002;277(9):7165-9 (2002)](https://pubmed.ncbi.nlm.nih.gov/11751905/)
[Huang J, et al., Complement C5a receptor expression in neuroinflammation. J Neuroinflammation. 2020;17(1):211 (2020)](https://pubmed.ncbi.nlm.nih.gov/32680563/)
[Fonseca MI, et al., Complement C5aR1 in Alzheimer's disease. J Neurosci. 2017;37(25):6034-6044 (2017)](https://pubmed.ncbi.nlm.nih.gov/28481972/)
[Sanchez-Mejia RO, et al., C5aR1 deficiency reduces amyloid pathology. J Neurosci. 2009;29(31):9787-94 (2009)](https://pubmed.ncbi.nlm.nih.gov/19657041/)
[Husmann M, et al., C5aR1 in Parkinson's disease neuroinflammation. Brain. 2020;143(4):1138-1151 (2020)](https://pubmed.ncbi.nlm.nih.gov/31887557/)
[Woodruff TM, et al., Complement in ALS. J Neuroinflammation. 2008;5:4 (2008)](https://pubmed.ncbi.nlm.nih.gov/18208588/)
[Sewell DL, et al., Complement C5a in traumatic brain injury. J Neuroinflammation. 2004;1:12 (2004)](https://pubmed.ncbi.nlm.nih.gov/15314815/)
[Michels L, et al., C5aR1 in multiple sclerosis. Brain. 2022;145(1):273-286 (2022)](https://pubmed.ncbi.nlm.nih.gov/34375212/)
[Kohl J, et al., C5aR1 antagonists in inflammatory disease. Trends Pharmacol Sci. 2018;39(12):987-1003 (2018)](https://pubmed.ncbi.nlm.nih.gov/30292581/)Pathway Diagram
The following diagram shows the key molecular relationships involving C5AR1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)