C1QC

protein-coding

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

Gene summary

This gene encodes the C-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q is composed of 18 polypeptide chains which include 6 A-chains, 6 B-chains, and 6 C-chains. Each chain contains an N-terminal collagen-like region and a C-terminal C1q globular domain. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. [provided by RefSeq, Dec 2016]

Previous symbols:

C1QG

MANE transcript

NM_172369.5

Inheritance

ClinVar variants

P:4U:76B:84

Top phenotype

C1q deficiency 3

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr1:22,643,014-22,648,110

External References & Databases

Ensembl (ENSG00000159189)

Transcript & Mutation Effects

hg38 • Region Span ~5.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

systemic lupus erythematosus related to C1QCDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:1060227

Submitter: ClinGen

*C1QC* encodes the C-chain of the complement component C1q, a core part of the C1 complex—the first component of the classical complement pathway. Together with C1r and C1s, C1q forms a complex essential for immune defense by recognizing immune complexes and initiating complement activation. *C1QC* was first reported in relation to autosomal recessive systemic lupus erythematosus (SLE) in 1995 (PMID: 7594474). Ten variants (3 nonsense, 2 frameshift, 1 in-frame deletion and 4 missense) that have been reported in 23 probands in 17 publications (PMIDs: 7594474, 8630118, 18682415, 20810037, 21654842, 24331529, 28082982, 30008451, 30608615, 30707351, 31357913, 31362757, 34993161, 36416474, 38263665, 39196411, 39470951) are included in this curation. These variants are identified in both homozygous and compound heterozygous states in affected individuals. All probands exhibit confirmed C1q deficiency, presenting with SLE or SLE-like clinical features. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is a loss of function. In affected individuals, the absence of functional C1q protein (e.g. PMID: 38263665) results in a complete loss of classical pathway hemolytic complement activity. In summary, there is **definitive** evidence supporting the relationship between *C1QC* and autosomal recessive Systemic Lupus Erythematosus. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Monogenic Systemic and Incomplete Lupus Erythematosus GCEP on the meeting date February 11, 2026 (SOP Version 11).

C1Q deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013343

Submitter: Labcorp Genetics (formerly Invitae)

C1Q deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013343

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

C1q deficiency 3AR

Manifestation: Allergy/Immunology/Infectious; Dermatologic; Renal

Intervention: Allergy/Immunology/Infectious

Rationale: 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

Comments: Individuals are also prone to glomerulonephritis and SLE

Refs: 6445507; 6319055; 8630118; 225968

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to C1QC variants in ClinVar

7 Conditions Cataloged

not providedTotal: 148

Inborn genetic diseasesTotal: 31

not specifiedTotal: 19

C1Q deficiencyTotal: 10

C1QC-related disorderTotal: 3

C1Q deficiency 3Total: 3

C1QC-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172369.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	77 clinvar		78
missense	1 clinvar		71 clinvar	6 clinvar	1 clinvar	79
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift		2 clinvar	3 clinvar			5
splice donor/acceptor (+/-2bp)						0
Total	2	2	76	83	1	164

Highest pathogenic variant AF is 0.000082124214

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172369.5	RefSeq	NP_758957.2	2	MANE Select
ENST00000374640.9	Ensembl	ENSP00000363771.4	2	MANE Select
NM_001114101.3	RefSeq	NP_001107573.1	2	Standard
NM_001347619.2	RefSeq	NP_001334548.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
c1qc	Danio rerio	Structure: blood circulation Quality: disrupted abnormal

Gene / Model

Organism

Observed Phenotype

c1qc

Danio rerio

Structure: blood circulation

Quality: disrupted

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

proteolysis
immune response
complement activation
complement activation, classical pathway
regulation of complement activation

Molecular Function

serine-type endopeptidase activity
protein binding

Cellular Component

extracellular region
collagen trimer
extracellular space
collagen-containing extracellular matrix
blood microparticle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374639
Coding exons: 2
Length: 4481
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.432	132	147	0.900	0.00000918	1543
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000082	0.000079	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.196

Intolerance Scores

LoFtool: 0.231
RVIS EVS: -0.58
RVIS percentile EVS: 18.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.427

Gene Damage Prediction

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