C5AR2
protein-codingcomplement C5a receptor 2, the group of Complement component GPCRs
Gene summary
This gene encodes a G-protein coupled receptor 1 family member involved in the complement system of the innate immune response. Unlike classical G-protein coupled receptors, the encoded protein does not associate with intracellular G-proteins. It may instead modulate signal transduction through the beta-arrestin pathway, and may alternatively act as a decoy receptor. This gene may be involved in coronary artery disease and in the pathogenesis of sepsis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]
- GPR77
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to C5AR2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001271749.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 12 | 2 | 14 | |||
| missense | 72 | 13 | 1 | 86 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 72 | 25 | 3 | 100 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001258678.1 | 1 | MANE Select | |
| Ensembl | ENSP00000472620.1 | 1 | MANE Select | |
| RefSeq | NP_001258679.1 | 1 | Standard | |
| RefSeq | NP_060955.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Other
- Human Complement System
- GPCRs, Class A Rhodopsin-like
- Signaling by GPCR
- Signal Transduction
Biological Process
- complement receptor mediated signaling pathway
- chemotaxis
- inflammatory response
- phospholipase C-activating G protein-coupled receptor signaling pathway
- positive regulation of cytosolic calcium ion concentration
Molecular Function
- complement component C5a receptor activity
- G protein-coupled receptor activity
- protein binding
Cellular Component
- plasma membrane
- basal plasma membrane
- integral component of membrane
- apical part of cell
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000595464
- Coding exons
- 1
- Length
- 11203
- Individuals with no LoFs
- 125634
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125646
- p
- 0.0000478
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.146 | 214 | 208 | 1.03 | 0.0000151 | 2092 |
| Missense (PolyPhen) | 61 | 63.127 | 0.9663 | 726 | ||
| Synonymous | -0.726 | 110 | 101 | 1.09 | 0.00000759 | 794 |
| Loss of Function | 1.19 | 1 | 3.35 | 0.298 | 2.32e-7 | 27 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000052 | 0.000046 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for the chemotactic and inflammatory C3a, C4a and C5a anaphylatoxin peptides and also for their dearginated forms ASP/C3adesArg, C4adesArg and C5adesArg respectively. Couples weakly to G(i)-mediated signaling pathways. {ECO:0000269|PubMed:11773063, ECO:0000269|PubMed:15833747, ECO:0000269|PubMed:19615750}.;
Recessive Scores
- pRec
- 0.153
Intolerance Scores
- RVIS EVS
- -0.33
- RVIS percentile EVS
- 30.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |