C1R

complement C1r, the group of Complement system activation components|Sushi domain containing

Basic information

Region (hg38): 12:7080214-7092540

Links

ENSG00000159403 ∙ NCBI:715 ∙ OMIM:613785 ∙ HGNC:1246 ∙ Uniprot:P00736 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ehlers-Danlos syndrome, periodontal type 1 (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, periodontal type 1 (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, periodontitis type (Supportive), mode of inheritance: AD
• autosomal systemic lupus erythematosus type 16 (Supportive), mode of inheritance: AD
• Ehlers-Danlos syndrome, periodontal type 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ehlers-Danlos syndrome, periodontal type 1	AD	Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal	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	Allergy/Immunology/Infectious; Cardiovascular; Dental; Dermatologic; Gastrointestinal; Musculoskeletal	27745832

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C1R gene.

• Ehlers-Danlos syndrome, periodontal type 1 (14 variants)
• Ehlers-Danlos syndrome, periodontal type 2 (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C1R gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				10	1	11
missense	11	3	23	7	3	47
nonsense						0
start loss						0
frameshift	1					1
inframe indel	2					2
splice donor/acceptor (+/-2bp)			1			1
splice region				1		1
non coding			1	7	11	19
Total	14	3	25	24	15

Variants in C1R

This is a list of pathogenic ClinVar variants found in the C1R region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-7080480-GT-G			Benign (May 10, 2021)
12-7080550-C-T			Likely benign (Jun 01, 2022)
12-7080559-G-C			Likely benign (Feb 01, 2024)
12-7080577-G-A		not specified	Likely benign (Nov 07, 2022)
12-7080637-C-T		C1R-related disorder	Likely benign (Feb 01, 2024)
12-7080650-C-T		not specified	Uncertain significance (Feb 27, 2023)
12-7080673-T-C		not specified	Likely benign (Jul 07, 2017)
12-7080724-G-C			Uncertain significance (Jul 12, 2023)
12-7081019-G-A			Uncertain significance (Mar 19, 2019)
12-7081221-A-AGG		Ehlers-Danlos syndrome, periodontal type 1	Pathogenic (-)
12-7081258-G-T			Benign (May 04, 2021)
12-7081476-GT-G			Benign (May 20, 2021)
12-7082043-C-T			Uncertain significance (Mar 01, 2022)
12-7082077-A-G		Ehlers-Danlos syndrome, periodontal type 1 • Ehlers-Danlos syndrome, periodontal type 2	Pathogenic (Aug 23, 2016)
12-7085919-GTAGTACTGGATACGG-TATTACATGA		Ehlers-Danlos syndrome, periodontal type 1 • Ehlers-Danlos syndrome, periodontal type 2	Pathogenic (Aug 23, 2016)
12-7085932-C-T		Ehlers-Danlos syndrome, periodontal type 1	Likely benign (Mar 31, 2022)
12-7086383-G-C		Ehlers-Danlos syndrome, periodontal type 1 • Ehlers-Danlos syndrome, periodontal type 2	Pathogenic (Aug 23, 2016)
12-7086404-C-G		Ehlers-Danlos syndrome, periodontal type 1 • Ehlers-Danlos syndrome, periodontal type 2	Pathogenic (Aug 23, 2016)
12-7086423-C-A		Ehlers-Danlos syndrome, periodontal type 1 • Ehlers-Danlos syndrome, periodontal type 2	Pathogenic (Aug 23, 2016)
12-7086423-C-T		Ehlers-Danlos syndrome, periodontal type 1	Likely pathogenic (Jan 27, 2023)
12-7088459-A-G			Benign (May 10, 2021)
12-7088490-T-C			Likely benign (Jul 01, 2024)
12-7088532-A-G			Benign (May 19, 2021)
12-7088615-T-G			Benign (May 04, 2021)
12-7088636-A-G		Ehlers-Danlos syndrome, periodontal type 1 • Ehlers-Danlos syndrome, periodontal type 2	Pathogenic (Sep 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C1R	protein_coding	protein_coding	ENST00000542285	10	57691

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.779	0.221	124622	0	28	124650	0.000112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.03	271	383	0.708	0.0000226	4278
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000211	0.000211
Ashkenazi Jewish	0.000103	0.0000994
East Asian	0.000176	0.000167
Finnish	0.000511	0.000511
European (Non-Finnish)	0.0000359	0.0000354
Middle Eastern	0.000176	0.000167
South Asian	0.0000376	0.0000327
Other	0.000334	0.000330

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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);Dengue-2 Interactions with Complement and Coagulation Cascades;Oxidative Damage;Complement Activation;Complement and Coagulation Cascades;classical complement pathway;Innate Immune System;Immune System;Initial triggering of complement;Classical antibody-mediated complement activation;Regulation of Complement cascade;Creation of C4 and C2 activators;Complement cascade (Consensus)

Haploinsufficiency Scores

• ghis: 0.531

Essentials

• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.503

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: C1rb

Gene ontology

• Biological process: immune response;complement activation;complement activation, classical pathway;regulation of complement activation;zymogen activation;innate immune response
• Cellular component: extracellular region;extracellular space;extracellular exosome;blood microparticle
• Molecular function: serine-type endopeptidase activity;calcium ion binding;protein binding;serine-type peptidase activity