C1QB

complement C1q B chain, the group of Complement system activation components|C1q domain containing

Basic information

Region (hg38): 1:22652761-22661637

Links

ENSG00000173369 ∙ NCBI:713 ∙ OMIM:120570 ∙ HGNC:1242 ∙ Uniprot:P02746 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• C1Q deficiency (Strong), mode of inheritance: AR
• C1Q deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
C1q deficiency 2	AR	Allergy/Immunology/Infectious	While the majority of sequelae may involve autoimmune manifestations (for which treatment with FFP may be beneficial), some individuals have been described with frequent and/or severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Dermatologic; Renal	6445507; 6319055; 2894352; 23651859
Individuals are also prone to glomerulonephritis and SLE

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C1QB gene.

• not provided (83 variants)
• Inborn genetic diseases (9 variants)
• C1Q deficiency (3 variants)
• C1QB-related condition (1 variants)
• C1Q deficiency 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C1QB 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			1	28	8	37
missense			38	3	1	42
nonsense						0
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	2	6	9
Total	0	1	41	33	15

Variants in C1QB

This is a list of pathogenic ClinVar variants found in the C1QB region.

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

Position	Type	Phenotype	Significance	ClinVar
1-22659292-AGATG-A			Benign (Jun 18, 2021)
1-22659292-A-AGATG			Benign (Jun 18, 2021)
1-22659292-A-AGATGGATG			Benign (Jun 18, 2021)
1-22659460-A-T			Uncertain significance (Oct 12, 2020)
1-22659475-T-G			Uncertain significance (Aug 19, 2022)
1-22659487-C-T		Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
1-22659499-T-C			Likely benign (Nov 13, 2023)
1-22659502-C-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2023)
1-22659513-G-A			Likely benign (Sep 16, 2022)
1-22659522-C-A		C1QB-related disorder	Benign (Jan 25, 2024)
1-22659522-C-T			Likely benign (Nov 25, 2023)
1-22659523-G-A		Inborn genetic diseases	Uncertain significance (Jan 20, 2023)
1-22659539-A-G			Uncertain significance (Jan 23, 2024)
1-22659540-G-C			Uncertain significance (Dec 14, 2023)
1-22659552-C-T			Likely benign (Dec 13, 2022)
1-22659553-G-A			Uncertain significance (Jul 09, 2022)
1-22659558-C-G			Likely benign (May 19, 2021)
1-22659564-C-G		C1QB-related disorder	Benign (Jan 29, 2024)
1-22659578-C-T			Uncertain significance (Aug 27, 2021)
1-22659579-G-A			Likely benign (Jan 11, 2024)
1-22659588-T-TG			Uncertain significance (Jul 19, 2022)
1-22659597-T-A			Likely benign (Dec 20, 2022)
1-22659603-C-T			Likely benign (Jul 19, 2022)
1-22659604-G-A			Uncertain significance (Jun 08, 2021)
1-22659618-G-A			Benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C1QB	protein_coding	protein_coding	ENST00000314933	2	8777

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.154	0.783	125731	0	12	125743	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.29	116	162	0.715	0.00000986	1643
Missense in Polyphen		36	68.649	0.52441		702
Synonymous	-0.583	74	67.9	1.09	0.00000448	542
Loss of Function	1.52	2	6.02	0.332	3.22e-7	70

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000622	0.0000615
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
• Disease: DISEASE: Complement component C1q deficiency (C1QD) [MIM:613652]: A disorder caused by impaired activation of the complement classical pathway. It generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis. {ECO:0000269|PubMed:9476130}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Prion diseases - Homo sapiens (human);Complement and coagulation cascades - Homo sapiens (human);Pertussis - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Staphylococcus aureus infection - Homo sapiens (human);Allograft Rejection;Spinal Cord Injury;Dengue-2 Interactions with Complement and Coagulation Cascades;Microglia Pathogen Phagocytosis Pathway;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)

Intolerance Scores

• loftool: 0.211
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.01

Haploinsufficiency Scores

• pHI: 0.165
• hipred: N
• hipred_score: 0.208
• ghis: 0.395

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0825

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: C1qb

Gene ontology

• Biological process: proteolysis;complement activation;complement activation, classical pathway;regulation of complement activation;innate immune response;inner ear development
• Cellular component: extracellular region;collagen trimer;complement component C1 complex;collagen-containing extracellular matrix;blood microparticle
• Molecular function: serine-type endopeptidase activity;protein binding;protein homodimerization activity