C1QC

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

Basic information

Region (hg38): 1:22643013-22648110

Previous symbols: [ "C1QG" ]

Links

ENSG00000159189 ∙ NCBI:714 ∙ OMIM:120575 ∙ HGNC:1245 ∙ Uniprot:P02747 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
C1q deficiency 3	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; 8630118; 225968
Individuals are also prone to glomerulonephritis and SLE

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C1QC gene.

• not provided (112 variants)
• C1Q deficiency (9 variants)
• Inborn genetic diseases (7 variants)
• C1Q deficiency 3 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C1QC 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	44	3	48
missense	1		50	2	1	54
nonsense	1		1			2
start loss						0
frameshift			2			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				1	7	8
Total	2	0	56	47	11

Highest pathogenic variant AF is 0.0000460

Variants in C1QC

This is a list of pathogenic ClinVar variants found in the C1QC region.

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

Position	Type	Phenotype	Significance	ClinVar
1-22644027-G-A			Uncertain significance (Nov 22, 2021)
1-22644027-G-T			Uncertain significance (Nov 25, 2023)
1-22644029-C-T			Likely benign (Dec 15, 2023)
1-22644031-T-C		C1Q deficiency	Conflicting classifications of pathogenicity (Dec 21, 2023)
1-22644037-C-G			Uncertain significance (Jun 25, 2022)
1-22644042-T-A			Likely benign (Nov 05, 2018)
1-22644042-T-AA		C1Q deficiency	Uncertain significance (Mar 30, 2021)
1-22644042-TC-AA		C1Q deficiency	Conflicting classifications of pathogenicity (Jan 25, 2024)
1-22644043-C-A			Likely benign (Nov 05, 2018)
1-22644046-T-C			Uncertain significance (Jul 15, 2022)
1-22644053-C-T			Likely benign (Dec 30, 2022)
1-22644065-G-A			Likely benign (Aug 17, 2023)
1-22644066-C-T			Likely benign (Mar 16, 2021)
1-22644071-G-A			Likely benign (Feb 18, 2022)
1-22644077-C-CCTG			Uncertain significance (Feb 19, 2022)
1-22644083-G-C			Likely benign (Sep 10, 2022)
1-22644113-A-G			Likely benign (Mar 23, 2022)
1-22644122-C-T			Likely benign (Dec 12, 2023)
1-22644123-G-A		C1Q deficiency	Pathogenic (Jan 09, 2024)
1-22644126-A-G			Uncertain significance (Feb 04, 2021)
1-22644140-C-T			Likely benign (Jul 09, 2023)
1-22644149-C-T			Benign (Feb 01, 2024)
1-22644170-G-T			Likely benign (Jun 25, 2022)
1-22644173-C-T			Likely benign (Oct 04, 2023)
1-22644175-A-T			Uncertain significance (Dec 19, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C1QC	protein_coding	protein_coding	ENST00000374639	2	4481

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0486	0.866	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.432	132	147	0.900	0.00000918	1543
Missense in Polyphen		46	62.228	0.73921		647
Synonymous	-1.03	86	74.7	1.15	0.00000600	538
Loss of Function	1.42	3	7.08	0.424	3.88e-7	81

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000823	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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:8630118}. 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;Dengue-2 Interactions with Complement and Coagulation Cascades;Microglia Pathogen Phagocytosis Pathway;Oxidative Damage;TYROBP Causal Network;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)

Recessive Scores

• pRec: 0.196

Intolerance Scores

• loftool: 0.231
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.44

Haploinsufficiency Scores

• pHI: 0.183
• hipred: N
• hipred_score: 0.201
• ghis: 0.487

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.427

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: C1qc

Zebrafish Information Network

• Gene name: c1qc
• Affected structure: blood circulation
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: proteolysis;immune response;complement activation;complement activation, classical pathway;regulation of complement activation;negative regulation of granulocyte differentiation;innate immune response;negative regulation of macrophage differentiation
• Cellular component: extracellular region;collagen trimer;extracellular space;collagen-containing extracellular matrix;blood microparticle
• Molecular function: serine-type endopeptidase activity;protein binding