C5AR2

Chr 19

complement C5a receptor 2

Also known as: C5L2, GPF77, GPR77

The C5AR2 protein is a G-protein coupled receptor that binds complement anaphylatoxins (C5a, C3a, C4a) and their dearginated forms, functioning as part of the innate immune system's complement cascade. Unlike typical GPCRs, it does not associate with intracellular G-proteins and may act as a decoy receptor or signal through beta-arrestin pathways to modulate inflammatory responses. No pediatric neurogenetic disorders have been definitively associated with C5AR2 mutations in the provided data.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.35
Clinical SummaryC5AR2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.35LOEUF
pLI 0.246
Z-score 1.19
OE 0.30 (0.101.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.15Z-score
OE missense 1.03 (0.921.15)
214 obs / 208.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.30 (0.101.35)
00.351.4
Missense OE1.03 (0.921.15)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 1 / 3.4Missense obs/exp: 214 / 208.1Syn Z: -0.73
DN
0.6937th %ile
GOF
0.73top 25%
LOF
0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

C5AR2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗