C2

complement C2, the group of Complement system activation components|Sushi domain containing

Basic information

Region (hg38): 6:31897785-31945673

Links

ENSG00000166278 ∙ NCBI:717 ∙ OMIM:613927 ∙ HGNC:1248 ∙ Uniprot:P06681 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complement component 2 deficiency (Strong), mode of inheritance: AR
• complement component 2 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Complement component 2 deficiency	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial for infectious manifestations; Patients may also develop autoimmune manifestations, and treatment with immune modulators has been described	Allergy/Immunology/Infectious; Renal	14446782; 4161820; 1124106; 2582254; 1542325; 1361318; 1577763; 8621452; 15643297; 16026838; 20417301; 20890976; 22842196

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C2 gene.

• not_provided (329 variants)
• not_specified (86 variants)
• Complement_component_2_deficiency (57 variants)
• Age_related_macular_degeneration_14 (46 variants)
• Macular_degeneration (10 variants)
• Atypical_hemolytic-uremic_syndrome (8 variants)
• C2-related_disorder (7 variants)
• C2_deficiency,_type_II (2 variants)
• Atypical_hemolytic-uremic_syndrome_with_B_factor_anomaly (1 variants)
• C2_deficiency,_type_I (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000063.6. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	3	86	1	91
missense	1		179	29		209
nonsense	6	1	2			9
start loss						0
frameshift	5	3				8
splice donor/acceptor (+/-2bp)	1	9		1		11
Total	13	14	184	116	1

Highest pathogenic variant AF is 0.0057364567

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C2	protein_coding	protein_coding	ENST00000299367	18	47888

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.35e-16	0.270	124496	2	1250	125748	0.00499

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	361	426	0.847	0.0000266	4954
Missense in Polyphen		128	169.65	0.75448		1985
Synonymous	1.06	151	168	0.896	0.0000108	1478
Loss of Function	1.42	30	39.6	0.757	0.00000232	421

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00503	0.00501
Ashkenazi Jewish	0.0115	0.0116
East Asian	0.000273	0.000272
Finnish	0.00520	0.00514
European (Non-Finnish)	0.00726	0.00725
Middle Eastern	0.000273	0.000272
South Asian	0.000559	0.000555
Other	0.00440	0.00441

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase.
• Disease: DISEASE: Complement component 2 deficiency (C2D) [MIM:217000]: A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. Skin and joint manifestations are common and renal disease is relatively rare. Patients with complement component 2 deficiency are also reported to have recurrent invasive infections. {ECO:0000269|PubMed:8621452, ECO:0000269|PubMed:9670930}. 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);Staphylococcus aureus infection - Homo sapiens (human);Allograft Rejection;Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Oxidative Damage;Complement Activation;Complement and Coagulation Cascades;classical complement pathway;lectin induced complement pathway;Innate Immune System;Immune System;Activation of C3 and C5;Initial triggering of complement;Regulation of Complement cascade;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.260
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.78

Haploinsufficiency Scores

• pHI: 0.219
• hipred: N
• hipred_score: 0.432
• ghis: 0.428

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.895

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: C2

Gene ontology

• Biological process: proteolysis;complement activation;complement activation, classical pathway;response to nutrient;regulation of complement activation;innate immune response;positive regulation of apoptotic cell clearance
• Cellular component: extracellular region;extracellular space;extracellular exosome
• Molecular function: serine-type endopeptidase activity;protein binding;metal ion binding