C1R: Complement C1r Subcomponent
Key Initiator of the Classical Complement Pathway
Gene Information Card
| Symbol | C1R |
|---|---|
| Full Name | Complement C1r Subcomponent |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.31 |
| NCBI Gene ID | 715 ncbi.nlm.nih.gov/gene/715 |
| Ensembl ID | ENSG00000159403 |
| UniProt ID | P00736 |
| OMIM ID | 613785 |
| HGNC ID | 1246 |
| Aliases | C1r, complement component 1r |
Description
The C1R gene encodes complement C1r, a serine protease that forms the C1 complex with C1q and C1s. Upon C1q binding to immune complexes, C1r autoactivates and cleaves C1s, initiating the classical complement pathway. This pathway is critical for pathogen opsonization, immune clearance, and inflammation. C1R deficiency is associated with immune complex diseases and connective tissue disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Periodontal Ehlers-Danlos syndrome | Loss-of-function mutations in C1R impair complement activation, leading to connective tissue fragility and severe periodontitis. | OMIM #130080; ClinVar |
| Systemic lupus erythematosus (SLE) | C1R deficiency reduces clearance of apoptotic cells and immune complexes, promoting autoimmunity. | OMIM #613785; NCBI Gene |
| Complement component 1r deficiency | Homozygous or compound heterozygous mutations cause absent C1r activity, increasing susceptibility to infections and SLE-like syndromes. | OMIM #613785; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Spleen | 8.3 | Medium |
| Lung | 6.1 | Medium |
| Kidney | 4.7 | Low |
| Heart | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocyte line; high expression |
| THP-1 | 9.8 | Monocyte line; moderate expression |
| A549 | 5.4 | Lung epithelial line; low expression |
| K562 | 2.1 | Erythroleukemia line; very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1157G>A (p.Trp386Ter) | Nonsense | Rare | Loss of function; truncation of serine protease domain |
| c.1342C>T (p.Arg448Cys) | Missense | Rare | Impaired catalytic activity; associated with periodontal Ehlers-Danlos syndrome |
| c.1A>G (p.Met1Val) | Missense (start loss) | Rare | Loss of translation initiation; complete deficiency |
Mutation functional classification
Loss of Function (LOF)
Most reported C1R mutations are loss-of-function, leading to reduced or absent C1r activity and impaired classical complement pathway.
Gain of Function (GOF)
No gain-of-function mutations have been documented in C1R.
Dominant Negative (DN)
No dominant-negative effects have been described for C1R mutations.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Classical complement pathway (Reactome: R-HSA-166663)
• Complement cascade (KEGG: hsa04610)
Protein Summary
Complement C1r is a 705-amino-acid serine protease synthesized as a zymogen. It consists of six domains: two CUB domains, an EGF-like domain, two CCP modules, and a serine protease domain. Upon C1 complex activation, C1r undergoes autoactivation via cleavage at Arg463-Ile464, generating an active form that cleaves C1s. The protein is primarily secreted by the liver and circulates in plasma. Structural defects in the serine protease domain impair catalytic function, leading to complement deficiency and disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| C1R Knockout HEK293 Cell Line | EDJ-KQ1987 | Human | 715 | Details Get a Quote |
| C1RL Knockout HEK293 Cell Line | EDJ-KQ2415 | Human | 51279 | Details Get a Quote |
| C1R Knockout A-549 Cell Line | EDJ-KQ21971 | Human | 715 | Details Get a Quote |
| C1R Knockout HCT 116 Cell Line | EDJ-KQ21972 | Human | 715 | Details Get a Quote |
| C1R Knockout HeLa Cell Line | EDJ-KQ21973 | Human | 715 | Details Get a Quote |
| C1RL Knockout HCT 116 Cell Line | EDJ-KQ22919 | Human | 51279 | Details Get a Quote |
| C1RL Knockout HeLa Cell Line | EDJ-KQ22920 | Human | 51279 | Details Get a Quote |
| C1RL Knockout A-549 Cell Line | EDJ-KQ21593 | Human | 51279 | Details Get a Quote |
