C1R
protein-codingcomplement C1r, the group of Complement system activation components|Sushi domain containing
Gene summary
This gene encodes a member of the peptidase S1 protein family. The encoded protein is a proteolytic subunit in the complement system C1 complex. The complement system acts as a mediator in the innate immune response by ultimately triggering phagocytosis, inflammation, and rupturing the bacterial cell wall. Mutations in this gene are associated with Ehlers-Danlos Syndrome. [provided by RefSeq, Dec 2018]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0020684
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0020684
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0007527
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0020684
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0013743
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Cardiovascular; Dental; Dermatologic; Gastrointestinal; Musculoskeletal
Intervention: Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal
Rationale: The condition has been described as inolving risk of arterial and gastrointestinal rupture, and awareness may allow prompt diagnosis and management; Individuals have been described as being prone to recurrent infections, and awareness may allow prompt diagnosis and management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to C1R variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001733.7. 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 | 33 | 7 | 40 | |||
| missense | 10 | 9 | 51 | 30 | 1 | 101 |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 11 | 9 | 55 | 63 | 9 | 147 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001724.4 | 11 | MANE Select | |
| Ensembl | ENSP00000497341.1 | 11 | MANE Select | |
| RefSeq | NP_001341275.1 | 11 | Standard | |
| Ensembl | ENSP00000438636.3 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Complement and coagulation cascades - Homo sapiens (human)
- Pertussis - Homo sapiens (human)
- Systemic lupus erythematosus - Homo sapiens (human)
- Phagosome - Homo sapiens (human)
- Staphylococcus aureus infection - Homo sapiens (human)
Biological Process
- immune response
- complement activation
- complement activation, classical pathway
- regulation of complement activation
- zymogen activation
Molecular Function
- serine-type endopeptidase activity
- calcium ion binding
- protein binding
- serine-type peptidase activity
Cellular Component
- extracellular region
- extracellular space
- extracellular exosome
- blood microparticle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000542285
- Coding exons
- 10
- Length
- 57691
- Individuals with no LoFs
- 124622
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 124650
- p
- 0.000112
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.03 | 271 | 383 | 0.708 | 0.0000226 | 4278 |
| Missense (PolyPhen) | 92 | 148.7 | 0.61871 | 1767 | ||
| Synonymous | -0.0472 | 160 | 159 | 1.00 | 0.0000102 | 1232 |
| Loss of Function | 3.92 | 5 | 27.0 | 0.185 | 0.00000115 | 321 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00018 | 0.00017 | rare |
| Finnish | 0.00051 | 0.00051 | rare |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000038 | 0.000033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.;
- Disease
- DISEASE: Ehlers-Danlos syndrome, periodontal type, 1 (EDSPD1) [MIM:130080]: A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSPD1 is characterized by the association of typical features of Ehlers-Danlos syndrome with gingival recession and severe early- onset periodontal disease, leading to premature loss of permanent teeth. EDSPD1 inheritance is autosomal dominant. {ECO:0000269|PubMed:27745832}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Essentials
- Essential (CRISPR2)
- S
- Indispensability pred.
- E
- Indispensability score
- 0.503
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |