C5AR1 Gene

C5AR1 Gene

Overview

C5AR1 Gene

Overview

<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"].

Gene Information

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]:

Signaling 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]:

C5aR1-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

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

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

Pathway Diagram

The following diagram shows the key molecular relationships involving C5AR1 Gene discovered through SciDEX knowledge graph analysis: