C1S Gene (Complement C1s)
Serine protease component of the classical complement pathway
Gene Information Card
| Symbol | C1S |
|---|---|
| Full Name | complement C1s |
| Gene Type | protein-coding |
| Chromosomal Location | 12p13.31 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000182326 |
| UniProt ID | P09871 |
| OMIM ID | 120580 |
| HGNC ID | 1247 |
| Aliases | C1s, complement component 1s subcomponent |
Description
The C1S gene encodes the C1s serine protease, which together with C1r and C1q forms the C1 complex of the classical complement pathway. Upon activation by C1q binding to immune complexes, C1r activates C1s, which then cleaves complement components C4 and C2 to initiate the downstream complement cascade. C1s is essential for innate immunity, clearance of apoptotic cells, and immune complex processing.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Complement component C1s deficiency | Loss-of-function mutations in C1S impair classical pathway activation, leading to increased susceptibility to recurrent infections and immune complex diseases. | OMIM #120580; PMID: 25457149 |
| Systemic lupus erythematosus (SLE) | Homozygous C1S deficiency is strongly associated with SLE due to defective clearance of apoptotic debris and immune complexes. | OMIM #120580; PMID: 24051380 |
| Periodontal Ehlers-Danlos syndrome | Missense mutations in C1S (e.g., p.Arg228His) cause a dominant-negative effect leading to connective tissue fragility and severe periodontitis. | OMIM #617174; PMID: 27652284 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | High |
| Spleen | 8.7 | Medium |
| Lung | 6.2 | Medium |
| Kidney | 4.5 | Low |
| Heart | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocyte cell line; high expression |
| THP-1 | 9.8 | Monocyte cell line; moderate expression |
| A549 | 5.4 | Lung epithelial cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1240C>T (p.Arg414Cys) | Missense | Rare | Loss of function; associated with C1s deficiency |
| c.683G>A (p.Arg228His) | Missense | Rare | Dominant-negative; causes periodontal Ehlers-Danlos syndrome |
| c.1A>G (p.Met1Val) | Missense | Rare | Loss of function; complete C1s deficiency |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that abolish C1s enzymatic activity or secretion, leading to complement deficiency and SLE.
Gain of Function (GOF)
Not reported for C1S.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg228His) that disrupt C1s folding or interaction with C1r/C1q, causing periodontal Ehlers-Danlos syndrome.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase activity (GO:0004252) | • classical pathway (GO:0006958) |
| • proteolysis (GO:0006508) | • extracellular region (GO:0005576) |
| • protein binding (GO:0005515) |
Pathways
• Classical complement pathway (KEGG: hsa04610)
• Complement and coagulation cascades (KEGG: hsa04610)
• Immune system (Reactome: R-HSA-168256)
Protein Summary
C1s is a 688-amino-acid serine protease (mature form) synthesized primarily in the liver and secreted into plasma. It contains an N-terminal CUB domain, an EGF-like domain, a second CUB domain, two CCP (complement control protein) modules, and a C-terminal serine protease domain. In the C1 complex, C1s is activated by C1r-mediated cleavage at Arg428-Ile429, generating a disulfide-linked two-chain active enzyme. Active C1s cleaves C4 and C2 to form the C3 convertase (C4b2a).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| C1S Knockout HEK293 Cell Line | EDJ-KQ4156 | Human | 716 | Details Get a Quote |
| C1S Knockout A-549 Cell Line | EDJ-KQ26593 | Human | 716 | Details Get a Quote |
| C1S Knockout HCT 116 Cell Line | EDJ-KQ26594 | Human | 716 | Details Get a Quote |
| C1S Knockout HeLa Cell Line | EDJ-KQ26595 | Human | 716 | Details Get a Quote |
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