C1R

Chr 12p13.31

complement C1r

MANE:: ENST00000647956.2

OMIM: 613785 ↗NCBI: 715 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

C1R · P00736

v62025-08-01

Predicted Aligned Error matrix for C1R — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

87.0/ 100

Confident

705 residues

Confidence breakdown

Very high(≥ 90)64%
Confident(70–90)24%
Low(50–70)7%
Very low(< 50)4%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ehlers Danlos syndrome with a likely monogenic cause
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Ehlers-Danlos syndrome, periodontitis type
0.71
immunodeficiency due to a classical component pathway complement deficiency
0.55
systemic lupus erythematosus
0.47
complement deficiency
0.46
Ehlers-Danlos syndrome, periodontal type 2
0.41
coronary artery disorder
0.39
Autosomal recessive systemic lupus erythematosus
0.37
Abdominal pain
0.30
Ehlers-Danlos syndrome
0.26
vascular dementia
0.14

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Complement C1r subcomponent

Serine protease component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:17996945, PubMed:19473974, PubMed:29449492). C1R catalyzes the first enzymatic step in the classical complement pathway: it is activated by the C1Q subcomplex of the C1 complex, which associates with IgG or IgM immunoglobulins complexed with antigens to form antigen-antibody complexes on the surface of pathogens (PubMed:29449492, PubMed:34155115). Immunoglobulin-binding promotes the autocatalytic cleavage and activation of C1R (PubMed:11445589, PubMed:11673533, PubMed:17996945, PubMed:20178990, PubMed:6254570, PubMed:6271784). Activated C1R then cleaves and activates C1S, the second protease of the classical complement pathway (PubMed:11445589, PubMed:11673533, PubMed:6271784). It is unclear if C1R activates C1S within single, strained C1 complexes or between neighboring C1 complexes on surfaces (PubMed:28104818, PubMed:29311313, PubMed:29449492)