C1QB
protein-codingcomplement C1q B chain, the group of Complement system activation components|C1q domain containing
Gene summary
This gene encodes the B-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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:1060228
Submitter: ClinGen
*C1QB* encodes the B-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. *C1QB* was first reported in relation to autosomal recessive systemic lupus erythematosus (SLE) in 1988 (PMID: 2894352). Seven variants (1 nonsense, 1 frameshift, 1 splicing and 4 missense) that have been reported in 8 probands in 8 publications (PMIDs: 2894352, 9476130, 17513176, 23651859, 24160257, 39470951, 39196411, 40506420) are included in this curation. These variants were identified in homozygous states in affected individuals. All probands exhibit confirmed C1q deficiency, presenting with SLE or SLE-like clinical features. *C1QB* variants have been shown to segregate with SLE in three families (PMIDs: 9476130, 17513176, 24160257). The mechanism of pathogenicity is loss of function. In affected individuals, the absence of functional C1q protein (e.g. PMID: 9476130) results in a total loss of classical pathway hemolytic complement activity. The addition of purified human C1q to patient plasma restored CH50 to a normal range (PMID: 24160257). Hematopoietic stem cell transplantation led to significant clinical recovery of patients with C1QB deficiency (PMID: 39470951). In summary, there is **definitive** evidence supporting the relationship between *C1QB* 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 January 14, 2026 (SOP Version 11).
Inheritance Pattern: AR
Disease ID:MONDO:0013343
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: Unknown
Disease ID:MONDO:0013343
Submitter: ClinGen
Clinical Genomic Database (CGD)
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to C1QB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001378156.1. 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 | 52 | 3 | 55 | |||
| missense | 3 | 80 | 6 | 89 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 1 | 3 | ||
| Total | 2 | 7 | 81 | 58 | 3 | 151 |
Highest pathogenic variant AF is 0.000047094924
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001365085.1 | 2 | MANE Select | |
| Ensembl | ENSP00000423689.1 | 2 | MANE Select | |
| RefSeq | NP_000482.3 | 2 | Standard | |
| RefSeq | NP_001358113.2 | 2 | Standard |
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
- complement activation
- complement activation, classical pathway
- regulation of complement activation
- innate immune response
Molecular Function
- serine-type endopeptidase activity
- protein binding
- protein homodimerization activity
Cellular Component
- extracellular region
- collagen trimer
- complement component C1 complex
- collagen-containing extracellular matrix
- blood microparticle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314933
- Coding exons
- 2
- Length
- 8777
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125743
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.29 | 116 | 162 | 0.715 | 0.00000986 | 1643 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Intolerance Scores
- LoFtool
- 0.211
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.01
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Indispensability pred.
- N
- Indispensability score
- 0.0825
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |