C1QA

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

Basic information

Region (hg38): 1:22635077-22639678

Links

ENSG00000173372 ∙ NCBI:712 ∙ OMIM:120550 ∙ HGNC:1241 ∙ Uniprot:P02745 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• C1Q deficiency (Moderate), 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 1	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; 7594474; 8840296; 9225968; 10776791; 20560256; 22576477
Individuals are also prone to autoimmune disease (eg, glomerulonephritis, SLE)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C1QA gene.

• not provided (5 variants)
• C1Q deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C1QA 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				40	3	43
missense		2	64	2		68
nonsense	1	1				2
start loss						0
frameshift	4	1	1			6
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2			2
non coding			1	6		7
Total	5	4	67	48	3

Variants in C1QA

This is a list of pathogenic ClinVar variants found in the C1QA region.

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

Position	Type	Phenotype	Significance	ClinVar
1-22637623-G-C			Uncertain significance (Dec 18, 2023)
1-22637627-C-G		C1Q deficiency	Uncertain significance (Jul 05, 2022)
1-22637629-C-T			Uncertain significance (Dec 26, 2020)
1-22637630-G-A			Uncertain significance (Jul 06, 2022)
1-22637632-G-A			Uncertain significance (Aug 31, 2021)
1-22637635-T-C			Uncertain significance (Mar 15, 2022)
1-22637640-G-A			Likely benign (Jun 03, 2023)
1-22637643-G-A			Likely benign (Nov 27, 2023)
1-22637655-G-A			Likely benign (Oct 17, 2022)
1-22637655-G-C			Likely benign (Sep 25, 2020)
1-22637663-C-T			Uncertain significance (Dec 26, 2020)
1-22637677-G-A			Uncertain significance (Mar 19, 2022)
1-22637682-C-T			Likely benign (Jul 27, 2022)
1-22637683-G-A		C1Q deficiency • C1QA-related disorder	Benign/Likely benign (Jan 31, 2024)
1-22637683-G-C			Uncertain significance (Dec 22, 2023)
1-22637695-C-G			Uncertain significance (Jul 14, 2022)
1-22637695-C-T		C1Q deficiency	Pathogenic/Likely pathogenic (Aug 10, 2023)
1-22637696-G-A			Uncertain significance (Aug 07, 2022)
1-22637706-C-T			Likely benign (Sep 08, 2023)
1-22637707-G-A			Uncertain significance (Jun 23, 2022)
1-22637729-G-A			Uncertain significance (Mar 18, 2022)
1-22637732-C-T			Uncertain significance (May 20, 2022)
1-22637736-C-A			Likely benign (Mar 10, 2022)
1-22637740-CG-C			Uncertain significance (Aug 22, 2022)
1-22637741-G-A			Uncertain significance (Aug 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C1QA	protein_coding	protein_coding	ENST00000374642	2	3103

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00382	0.862	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.29	106	151	0.703	0.00000944	1535
Missense in Polyphen		18	43.742	0.4115		454
Synonymous	0.554	58	63.6	0.912	0.00000427	528
Loss of Function	1.26	5	9.11	0.549	6.61e-7	81

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000292	0.0000292
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000811	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.000359	0.000359
Other	0.000166	0.000163

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. 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;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: 0.383
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

• pHI: 0.186
• hipred: N
• hipred_score: 0.238
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0298

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: C1qa
• Phenotype: renal/urinary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: proteolysis;complement activation;complement activation, classical pathway;cell-cell signaling;response to iron ion;regulation of complement activation;innate immune response
• Cellular component: extracellular region;collagen trimer;complement component C1 complex;collagen-containing extracellular matrix
• Molecular function: serine-type endopeptidase activity;protein binding