Alt. symbols: EDSPD1

Approved name: complement C1r
Alt. names: complement component 1, r subcomponent

Location: 12p13.31: 7080214 - 7092540 (-)
Gene type: protein_coding, 16 transcripts.

Scores: LoFtool: | pLI: 0.77888000 | LOEUF: 0.390

HGNC: 1246

NCBI: 715, RefSeq: NG_062465.1

Ensembl: ENSG00000159403.18

LRG_1321 | Status: public

OMIM: 613785

Expression | ProteinAtlas

C1R encodes the proteolytic subunit C1r of the C1 complex, which is the first component of the classical pathway of the complement system. As a member of the peptidase S1 protein family, C1r combines together with C1q and C1s to form the multimolecular C1 complex. The complement system acts as a mediator in the innate immune response by ultimately triggering phagocytosis, inflammation, and rupturing of the bacterial cell wall. After binding to a pathogen, C1r first autoactivates and then converts C1s to its active form by proteolytic cleavage.

Monoallelic mutations in the gene are associated with the development of Ehlers-Danlos syndrome, periodontal type, 1 (EDSPD1) [MIM:130080]. EDSPD1 is an autosomal dominant disorder characterized by the typical features of Ehlers-Danlos syndrome (hyperextensible skin, atrophic cutaneous scars and joint hyperlaxity) with gingival recession and severe early-onset periodontal disease, leading to premature loss of permanent teeth. The first reported EDSPD1-affected individuals (from 15 unrelated fami lies) were found to carry heterozygous missense or in-frame insertion/deletion mutations in C1R, which segregated with disease and were not found in the ExAC, 1000 Genomes Project, ClinVar, or dbSNP databases (Kapferer-Seebacher et al., 2016). In detail, 12 missense mutations (p.Val50Asp, p.Asp290Gly, p.Gly297Asp, p.Leu300Pro, p.Arg301Pro, p.Tyr302Cys, p.Cys309Trp, p.Cys338Arg, p.Cys358Phe, p.Trp364Cys, p.Cys371Trp and p.Trp435Arg) and two insertion/deletion mutations (p.Ile306_Cys309del-insArgArg and p.Arg401_Tyr405del-insHisValIle) were identified. Another missense variant, p.Cys276Arg, was identified in all three affected members of a Chinese family with clinical features of EDSPD1, whereas in the three healthy members of that family, the variant was not present (Wu et al., 2018). [Load More]