C1QB

Summary

C1QB (complement C1q B chain, HGNC:1242) is a protein-coding gene on chromosome 1p36.12, encoding Complement C1q subcomponent subunit B (P02746). Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

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.

Source: NCBI Gene 713 — RefSeq curated summary.

At a glance

• Gene–disease (curated): C1Q deficiency (Definitive, ClinGen)
• Clinical variants (ClinVar): 155 total — 2 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 26
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001378156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1242
Approved symbol	C1QB
Name	complement C1q B chain
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000173369
Ensembl biotype	protein_coding
OMIM	120570
Entrez	713

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 21 protein_coding

ENST00000432749, ENST00000509305, ENST00000510260, ENST00000695754, ENST00000695755, ENST00000695756, ENST00000695757, ENST00000695758, ENST00000695759, ENST00000695760, ENST00000695761, ENST00000695762, ENST00000695763, ENST00000897310, ENST00000897311, ENST00000897312, ENST00000897313, ENST00000897314, ENST00000952201, ENST00000952202, ENST00000952203

RefSeq mRNA: 3 — MANE Select: NM_001378156 NM_000491, NM_001371184, NM_001378156

CCDS: CCDS90878

Canonical transcript exons

ENST00000509305 — 3 exons

Exon	Start	End
ENSE00001273267	22659440	22659643
ENSE00003964933	22660812	22661637
ENSE00003964936	22653236	22653303

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 99.42.

FANTOM5 (CAGE): breadth broad, TPM avg 89.7124 / max 19760.7187, expressed in 417 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1316	87.0144	416
1326	0.6789	170
1320	0.4210	124
1315	0.3293	121
1313	0.1962	78
1329	0.1642	65
1325	0.1537	67
1327	0.1438	46
1322	0.1065	45
1314	0.0905	28

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.42	gold quality
spleen	UBERON:0002106	99.40	gold quality
decidua	UBERON:0002450	99.17	gold quality
right coronary artery	UBERON:0001625	99.03	gold quality
gall bladder	UBERON:0002110	98.98	gold quality
right adrenal gland cortex	UBERON:0035827	98.94	gold quality
right adrenal gland	UBERON:0001233	98.68	gold quality
upper lobe of left lung	UBERON:0008952	98.63	gold quality
upper lobe of lung	UBERON:0008948	98.52	gold quality
mucosa of stomach	UBERON:0001199	98.35	gold quality
left adrenal gland	UBERON:0001234	98.22	gold quality
left adrenal gland cortex	UBERON:0035825	98.22	gold quality
lymph node	UBERON:0000029	98.11	gold quality
lower lobe of lung	UBERON:0008949	97.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.87	gold quality
descending thoracic aorta	UBERON:0002345	97.85	gold quality
adrenal cortex	UBERON:0001235	97.74	gold quality
left coronary artery	UBERON:0001626	97.62	gold quality
coronary artery	UBERON:0001621	97.55	gold quality
omental fat pad	UBERON:0010414	97.47	gold quality
peritoneum	UBERON:0002358	97.41	gold quality
middle frontal gyrus	UBERON:0002702	97.35	gold quality
pericardium	UBERON:0002407	97.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.13	gold quality
thoracic aorta	UBERON:0001515	97.12	gold quality
vermiform appendix	UBERON:0001154	97.07	gold quality
transverse colon	UBERON:0001157	96.99	gold quality
ascending aorta	UBERON:0001496	96.94	gold quality
adrenal gland	UBERON:0002369	96.76	gold quality
small intestine	UBERON:0002108	96.72	gold quality

Single-cell (SCXA)

Detected in 40 experiment(s), a significant marker in 40.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	13888.98
E-MTAB-10553	yes	11597.57
E-CURD-122	yes	10317.88
E-MTAB-7407	yes	9984.04
E-MTAB-6308	yes	9805.07
E-GEOD-149689	yes	9779.73
E-GEOD-135922	yes	9272.48
E-HCAD-15	yes	9241.99
E-MTAB-6653	yes	7615.67
E-CURD-126	yes	7397.41
E-HCAD-9	yes	7186.88
E-MTAB-8322	yes	7091.05
E-CURD-98	yes	6104.31
E-MTAB-6701	yes	5655.23
E-MTAB-9906	yes	5615.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF8, SPI1, STAT1

miRNA regulators (miRDB)

20 targeting C1QB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-1293	96.16	64.69	916
HSA-MIR-6835-5P	95.81	64.27	500

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 28)

• Experiments with recombinant globular head domains of human C1q A, B, and C chains indicated that C1q interacts with PTX3 via its globular head region. Binding of C1q to immobilized PTX3 induced activation of the classical complement pathway. (PMID:12645945)
• The C-terminal globular region of the C1Q B chain may have evolved as a functionally specialized domain or module with distinct binding properties which together with the A and C chains confers versatility and flexibility to the whole C1q molecule. (PMID:12847249)
• The structure refined to 1.9 A of resolution of C1q reveals the conformation of subunits A, B, and C and their compact, almost spherical heterotrimeric assembly held together mainly by non-polar interactions, with a Ca2+ ion bound at the top. (PMID:12960167)
• Complementary interacting sites on the C1q globular domain have been precisely defined. Characterization of point mutants suggests a central role for Arg114 and a complementary role for Arg129, Arg163, and His117 of C1Q B chain in the C1q-IgG interaction. (PMID:15034050)
• The first analysis of C1q by mass spectrometry yields evidence that the B chain moiety of the globular head is involved in the interaction with fucoidan and underscores the particular role of arginine-109 in the charge pattern recognition property of C1q. (PMID:15709773)
• results suggest that charged residues belonging to the apex of the gC1q heterotrimer (with participation of all three chains) as well as the side of the ghB are crucial for C1q binding to ligands, IgG1, C-reactive protein, and pentraxin 3. (PMID:16566583)
• No C1q or low molecular weight C1q was detected in sera and no anti-C1q autoantibodies were found. Sequencing of the C1q genes revealed a novel missense mutation (Gly-Arg) in codon 217 of the B chain. (PMID:17513176)
• Data show that C1q, C4, C3, and C9 bind to thrombin receptor-activating peptide-activated platelets in lepirudin-anticoagulated platelet-rich plasma (PRP) and whole blood. (PMID:20139276)
• In a large family-based association study of C1Q gene cluster polymorphisms no evidence for a genetic role of C1Q locus SNP in systemic lupus erythematosus risk predisposition was obtained in patients of European ancestry. (PMID:20528885)
• a 2-gene signature consisting of PLEK2 and C1QB led to the best result that correctly classified 93.3% melanoma patients and 90% healthy controls (PMID:21698244)
• analysis of the molecular mechanisms for synchronized transcription of three complement C1q subunit genes (A, B and C) in dendritic cells and macrophages (PMID:21862594)
• The susceptibility for schizophrenia was particularly associated with C1QB rs291982 GG genotype. (PMID:21951915)
• We identified a major linear epitope of C1q that is the target of anti-C1q in systemic lupus erythematosus. (PMID:22740328)
• Single nucleotide polymorphisms in and around the C1q genes, C1qA, C1qB and C1qC, correlated with C1q serum levels and may be a risk for the development of rheumatoid arthritis. (PMID:23607884)
• Analysis of its interaction properties by surface plasmon resonance shows that rC1q retains the ability of serum C1q to associate with the C1s-C1r-C1r-C1s tetramer, to recognize physiological C1q ligands such as IgG and pentraxin 3 (PMID:23650384)
• Data indicate that Cna binds to C1q. (PMID:23720782)
• PepO facilitates C1q-mediated bacterial adherence, whereas its localized release consumes complement as a result of its activation following binding of C1q, thus representing an additional mechanism of human complement escape by this versatile pathogen. (PMID:24739385)
• no significant association found to either rs15940 (C1QA) or rs172378 (C1QC) when analysed in just Parkinson disease cases , just controls or combined (PMID:25817358)
• C1QB expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• results suggested that four differentially expressed genes, Jun, Gal, Cd74, and C1qb, had the potential to serve as prognostic or predictive markers for neuropathic pain, suggesting a potential application in the improvement of prognostic tools and treatments. (PMID:29331040)
• C1Q polymorphisms are associated with systemic lupus erythematosus. (PMID:29795138)
• The C allele at the rs631090 locus of C1q, the G allele at 1525A/G site of TRAIL, and the G allele of Tim-1 at -1454G/A site are susceptibility variants associated with SLE. the frequency of the T allele at the rs631090 locus in the study group was lower than that in the controls, and the frequency of the C allele was higher in the study group than in the healthy donors. (PMID:30183357)
• C1q-binding DSA and allograft outcomes in pediatric kidney transplant recipients. (PMID:33131194)
• Clinical and prognostic significance of C1q deposition in IgAN patients-a retrospective study. (PMID:33182045)
• Neuroinflammation and psychiatric disorders: Relevance of C1q, translocator protein (18 kDa) (TSPO), and neurosteroids. (PMID:34320915)
• Activation of complement C1q and C3 in glomeruli might accelerate the progression of diabetic nephropathy: Evidence from transcriptomic data and renal histopathology. (PMID:34932275)
• C1QA, C1QB, and GZMB are novel prognostic biomarkers of skin cutaneous melanoma relating tumor microenvironment. (PMID:36443341)
• Identifying C1QB, ITGAM, and ITGB2 as potential diagnostic candidate genes for diabetic nephropathy using bioinformatics analysis. (PMID:37250717)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	C1qb	ENSMUSG00000036905
rattus_norvegicus	C1qb	ENSRNOG00000012749

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), COL8A2 (ENSG00000171812), C1QTNF4 (ENSG00000172247), C1QA (ENSG00000173372), C1QTNF1 (ENSG00000173918), ADIPOQ (ENSG00000181092), OTOL1 (ENSG00000182447), C1QTNF8 (ENSG00000184471), C1QL4 (ENSG00000186897), C1QTNF9B (ENSG00000205863), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Complement C1q subcomponent subunit B — P02746 (reviewed: P02746)

All UniProt accessions (9): A0A0A0MSV6, A0A8Q3SI33, A0A8Q3SI50, A0A8Q3SI72, A0A8Q3WKR5, A0A8Q3WLT6, A0A8Q3WM25, D6R934, D6RGJ1

UniProt curated annotations — full annotation on UniProt →

Function. Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. The classical complement pathway is initiated by the C1Q subcomplex of the C1 complex, which specifically binds IgG or IgM immunoglobulins complexed with antigens, forming antigen-antibody complexes on the surface of pathogens: C1QA, together with C1QB and C1QC, specifically recognizes and binds the Fc regions of IgG or IgM via its C1q domain. Immunoglobulin-binding activates the proenzyme C1R, which cleaves C1S, initiating the proteolytic cascade of the complement system. The C1Q subcomplex is activated by a hexamer of IgG complexed with antigens, while it is activated by a pentameric IgM. The C1Q subcomplex also recognizes and binds phosphatidylserine exposed on the surface of cells undergoing programmed cell death, possibly promoting activation of the complement system.

Subunit / interactions. Core component of the complement C1 complex, a calcium-dependent complex composed of 1 molecule of the C1Q subcomplex, 2 molecules of C1R and 2 molecules of C1S. The C1Q subcomplex is composed 18 subunits: 3 chains of C1QA, C1QB, and C1QC trimerize to form 6 collagen-like triple helices connected to six globular ligand-recognition modules (C1q domain).

Subcellular location. Secreted. Cell surface.

Post-translational modifications. Hydroxylated on lysine and proline residues. Hydroxylated lysine residues can be glycosylated. Human C1Q contains up to 68.3 hydroxylysine-galactosylglucose residues and up to 2.5 hydroxylysine-galactose per molecule. Total percentage hydroxylysine residues glycosylated is 86.4%.

Disease relevance. C1q deficiency 2 (C1QD2) [MIM:620321] An autosomal recessive disorder caused by impaired activation of the complement classical pathway. It generally leads to severe immune complex disease characterized by recurrent skin lesions, chronic infections, an increased risk of systemic lupus erythematosus, and glomerulonephritis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The C1Q subcomplex is inhibited by sulfated molecules, such as triterpenoid sulfates, heparan sulfate, or chondroitin sulfates.

Domain organisation. The C1q domain is the ligand-recognition domain, which specifically recognizes and binds the Fc regions of IgG or IgM immunoglobulins. The collagen-like domain interacts with C1R and C1S proenzymes.

RefSeq proteins (3): NP_000482, NP_001358113, NP_001365085* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008160	Collagen	Repeat
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR050392	Collagen/C1q_domain	Family

Pfam: PF00386, PF01391

UniProt features (50 total): modified residue 18, strand 10, binding site 3, domain 3, sequence conflict 3, compositionally biased region 3, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, mutagenesis site 1, helix 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2WNV	X-RAY DIFFRACTION	1.25
5HKJ	X-RAY DIFFRACTION	1.35
5HZF	X-RAY DIFFRACTION	1.55
1PK6	X-RAY DIFFRACTION	1.85
2JG9	X-RAY DIFFRACTION	1.9
2JG8	X-RAY DIFFRACTION	2.05
6Z6V	X-RAY DIFFRACTION	2.19
2WNU	X-RAY DIFFRACTION	2.3
9C9L	ELECTRON MICROSCOPY	3.7
9C9U	ELECTRON MICROSCOPY	4.5
6FCZ	ELECTRON MICROSCOPY	10

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02746-F1	79.87	0.51

Antibody-complex structures (SAbDab): 1 — 6Z6V

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 200; 206; 199

Post-translational modifications (18): 28, 35, 38, 41, 53, 56, 59, 62, 65, 77, 83, 86, 92, 98, 101, 104, 107, 110

Disulfide bonds (2): 31, 181–198

Mutagenesis-validated functional residues (1):

Position	Phenotype
88	in lysb61; impaired ability to associate with c1r and c1s.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-166663	Initial triggering of complement
R-HSA-173623	Classical antibody-mediated complement activation
R-HSA-977606	Regulation of Complement cascade

MSigDB gene sets: 348 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, GOCC_COLLAGEN_TRIMER, REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS, GOCC_CELL_SURFACE, IVANOVA_HEMATOPOIESIS_MATURE_CELL, WIELAND_UP_BY_HBV_INFECTION, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY, MODULE_66, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, MARTINEZ_RB1_TARGETS_UP, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (5): complement activation (GO:0006956), complement activation, classical pathway (GO:0006958), innate immune response (GO:0045087), synapse pruning (GO:0098883), inner ear development (GO:0048839)

GO Molecular Function (5): phosphatidylserine binding (GO:0001786), IgM binding (GO:0001791), IgG binding (GO:0019864), protein binding (GO:0005515), identical protein binding (GO:0042802)

GO Cellular Component (14): extracellular region (GO:0005576), collagen trimer (GO:0005581), complement component C1 complex (GO:0005602), cell surface (GO:0009986), extracellular matrix (GO:0031012), synapse (GO:0045202), complement component C1q complex (GO:0062167), blood microparticle (GO:0072562), postsynapse (GO:0098794), symbiont cell surface (GO:0106139), membrane (GO:0016020), extrinsic component of presynaptic membrane (GO:0098888), extrinsic component of postsynaptic membrane (GO:0098890), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Complement cascade	2
Creation of C4 and C2 activators	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
immunoglobulin binding	2
extracellular protein-containing complex	2
synapse	2
extrinsic component of synaptic membrane	2
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
humoral immune response mediated by circulating immunoglobulin	1
complement activation	1
immune response	1
defense response to symbiont	1
synapse organization	1
cell junction disassembly	1
ear development	1
anatomical structure development	1
phospholipid binding	1
anion binding	1
modified amino acid binding	1
binding	1
protein binding	1
protein-containing complex	1
complement component C1q complex	1
external encapsulating structure	1
cell junction	1
extracellular region	1
other organism part	1
presynaptic membrane	1
postsynaptic membrane	1

Protein interactions and networks

STRING

2230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QB	C1QA	P02745	984
C1QB	C1QC	P02747	983
C1QB	C1S	P09871	880
C1QB	C1R	P00736	879
C1QB	APOD	P05090	778
C1QB	CSTB	P04080	766
C1QB	SERPING1	P05155	729
C1QB	C4A	P01028	728
C1QB	MT2A	P02795	720
C1QB	CTSS	P25774	704
C1QB	TYROBP	O43914	689
C1QB	C4A	P01028	679
C1QB	APOE	P02649	655
C1QB	ITGB2	P05107	620
C1QB	B2M	P01884	599

IntAct

32 interactions, top by confidence:

A	B	Type	Score
C1QA	C1QB	psi-mi:“MI:0915”(physical association)	0.810
C1QA	C1QB	psi-mi:“MI:0914”(association)	0.810
C1QA	C1QB	psi-mi:“MI:0407”(direct interaction)	0.810
C1QBP	C1QB	psi-mi:“MI:0407”(direct interaction)	0.580
C1QB	C1QBP	psi-mi:“MI:0407”(direct interaction)	0.580
C1QBP	C1QB	psi-mi:“MI:0403”(colocalization)	0.580
C1QB	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
CD33	C1QA	psi-mi:“MI:0915”(physical association)	0.520
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
RELA	C1QB	psi-mi:“MI:0915”(physical association)	0.370
C1QB	EDA2R	psi-mi:“MI:0915”(physical association)	0.370
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
C1QB	FN1	psi-mi:“MI:0914”(association)	0.350
S	IGLL5	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
UBE2U	IGLL5	psi-mi:“MI:0914”(association)	0.350
C1QB	MANBA	psi-mi:“MI:0914”(association)	0.350
C1QB	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
	C1QB	psi-mi:“MI:0915”(physical association)	0.000
sbcD	C1QB	psi-mi:“MI:0915”(physical association)	0.000
C1QB	olgH	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (95): C1QB (Two-hybrid), C1QB (Affinity Capture-MS), ATP12A (Affinity Capture-MS), METAP2 (Affinity Capture-MS), COLGALT2 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), FN1 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), USP30 (Affinity Capture-MS), GK (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), LEPREL2 (Affinity Capture-MS), VHL (Affinity Capture-MS), VHL (Affinity Capture-MS), FN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, P02745, P02746, P02747, P08125, P0C862, P12106, P14106, P20849, P23206, P23805, P31720, P31721, P31722, P35246, P35247, P35248, P42916, P50404, P83371, P98085, P98086, Q02105, Q05306, Q05722, Q0II24, Q0VF58, Q14993, Q15848, Q1PBC5, Q2KIV9, Q3Y5Z3, Q4ZJM7, Q4ZJN1, Q5E9E3, Q60994, Q641F3

Diamond homologs: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, O75973, O88992, P02745, P02746, P08125, P0C862, P14106, P14282, P23206, P25067, P25318, P27658, P31720, P31721, P83371, P98085, P98086, Q00780, Q02105, Q03692, Q05306, Q05A80, Q06575, Q06576, Q06577, Q0II24, Q15848, Q2KIU3, Q2KIX7, Q3Y5Z3, Q4ZJM7, Q4ZJM9, Q4ZJN1, Q5E9E3, Q5FVH0, Q5RJ80

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
C1QB	“form complex”	“Complement C1q”	binding
C1QBP	“down-regulates activity”	C1QB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Innate Immune System	5	8.0×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

155 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	5
Uncertain significance	78
Likely benign	47
Benign	13

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
440741	NM_001378156.1(C1QB):c.181+1G>T	Pathogenic
4685007	NM_001378156.1(C1QB):c.174del (p.Glu59fs)	Pathogenic
17072	NM_001378156.1(C1QB):c.523C>T (p.Arg175Ter)	Likely pathogenic
3580835	NM_001378156.1(C1QB):c.181+1G>A	Likely pathogenic
3580849	NM_001378156.1(C1QB):c.262G>A (p.Gly88Ser)	Likely pathogenic
424891	NM_001378156.1(C1QB):c.394del (p.Leu132fs)	Likely pathogenic
440742	NM_001378156.1(C1QB):c.724G>A (p.Gly242Arg)	Likely pathogenic

SpliceAI

325 predictions. Top by Δscore:

Variant	Effect	Δscore
1:22659434:CCACA:C	acceptor_loss	1.0000
1:22659438:AGG:A	acceptor_loss	1.0000
1:22659636:A:T	donor_gain	1.0000
1:22660807:TCCA:T	acceptor_loss	1.0000
1:22660810:A:AT	acceptor_loss	1.0000
1:22660811:G:GC	acceptor_loss	1.0000
1:22653299:CCCAG:C	donor_loss	0.9900
1:22653302:AGGT:A	donor_loss	0.9900
1:22653303:GGTG:G	donor_loss	0.9900
1:22653304:GTG:G	donor_loss	0.9900
1:22653305:T:A	donor_loss	0.9900
1:22659438:A:AG	acceptor_gain	0.9900
1:22659438:AG:A	acceptor_gain	0.9900
1:22659438:AGGAG:A	acceptor_gain	0.9900
1:22659439:G:GG	acceptor_gain	0.9900
1:22659439:GG:G	acceptor_gain	0.9900
1:22659439:GGA:G	acceptor_gain	0.9900
1:22659439:GGAGG:G	acceptor_gain	0.9900
1:22659626:GGA:G	donor_gain	0.9900
1:22659642:AGGTA:A	donor_loss	0.9900
1:22659643:GG:G	donor_loss	0.9900
1:22659644:G:A	donor_loss	0.9900
1:22660810:A:AG	acceptor_gain	0.9900
1:22660810:AG:A	acceptor_gain	0.9900
1:22660810:AGG:A	acceptor_gain	0.9900
1:22660811:G:GG	acceptor_gain	0.9900
1:22660811:GG:G	acceptor_gain	0.9900
1:22660811:GGG:G	acceptor_gain	0.9900
1:22660811:GGGC:G	acceptor_gain	0.9900
1:22659436:ACAG:A	acceptor_gain	0.9800

AlphaMissense

1630 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:22661103:T:C	F160S	0.997
1:22660994:T:C	F124L	0.996
1:22660995:T:C	F124S	0.996
1:22660996:C:A	F124L	0.996
1:22660996:C:G	F124L	0.996
1:22661103:T:G	F160C	0.996
1:22661133:T:C	F170S	0.996
1:22661048:T:C	F142L	0.995
1:22661050:C:A	F142L	0.995
1:22661050:C:G	F142L	0.995
1:22661126:T:G	Y168D	0.995
1:22661342:A:C	S240R	0.995
1:22661344:C:A	S240R	0.995
1:22661344:C:G	S240R	0.995
1:22660995:T:G	F124C	0.994
1:22661049:T:C	F142S	0.994
1:22661102:T:C	F160L	0.994
1:22661104:C:A	F160L	0.994
1:22661104:C:G	F160L	0.994
1:22661110:C:G	C162W	0.993
1:22661265:T:C	L214P	0.993
1:22661289:T:A	V222D	0.993
1:22661349:T:C	F242S	0.993
1:22661354:G:T	G244W	0.993
1:22661357:T:C	F245L	0.993
1:22661359:C:A	F245L	0.993
1:22661359:C:G	F245L	0.993
1:22661165:T:A	C181S	0.992
1:22661166:G:C	C181S	0.992
1:22661216:T:A	C198S	0.992

dbSNP variants (sampled 300 via entrez): RS1000208895 (1:22656899 G>A), RS1000519920 (1:22656602 C>A), RS1000602760 (1:22660744 A>G), RS1000714519 (1:22653764 G>A), RS1000916810 (1:22661874 T>C), RS1001119914 (1:22655108 A>T), RS1001189332 (1:22653956 CA>C), RS1001306745 (1:22657886 T>C), RS1001436182 (1:22651429 A>C,G), RS1001568214 (1:22651647 C>A,T), RS1001744505 (1:22657842 T>C), RS1001819870 (1:22651840 T>A,C,G), RS1002284615 (1:22659397 A>G), RS1002314386 (1:22659672 A>C), RS1002345936 (1:22656182 T>C)

Disease associations

OMIM: gene MIM:120570 | disease phenotypes: MIM:620321, MIM:613652, MIM:219700

GenCC curated gene-disease

Disease	Classification	Inheritance
C1Q deficiency	Definitive	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
C1Q deficiency	Definitive	AR

Mondo (4): C1Q deficiency 2 (MONDO:0958187), C1Q deficiency (MONDO:0013343), cystic fibrosis (MONDO:0009061), C1Q deficiency 1 (MONDO:0958182)

Orphanet (1): Cystic fibrosis (Orphanet:586)

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000155	Oral ulcer
HP:0000403	Recurrent otitis media
HP:0001041	Facial erythema
HP:0001369	Arthritis
HP:0001903	Anemia
HP:0002110	Bronchiectasis
HP:0002783	Recurrent lower respiratory tract infections
HP:0002829	Arthralgia
HP:0002923	Rheumatoid factor positive
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0007417	Discoid lupus rash
HP:0009710	Chilblains
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0011463	Childhood onset
HP:0020102	Pneumocystis jirovecii pneumonia
HP:0025300	Malar rash
HP:0025434	Reduced circulating CH50 activity
HP:0033040	Anti-Sm antibody positivity
HP:0033399	Persistent fever
HP:0033476	Extractable nuclear antigen positivity
HP:0034601	Decreased circulating C1q concentration
HP:0100750	Atelectasis
HP:0100806	Sepsis
HP:0200029	Vasculitis in the skin

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	affects binding, increases expression	3
Zinc	affects binding, increases expression	2
propionaldehyde	decreases expression	1
peroben	affects binding, increases activity	1
nimesulide	increases expression, decreases reaction	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
nickel sulfate	decreases expression	1
monomethylpropion	increases expression	1
Arsenic Trioxide	increases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	affects binding	1
Calcitriol	decreases expression	1
Cholic Acids	affects cotreatment, affects expression	1
Methotrexate	decreases expression	1
Naled	affects expression	1
Selenium	increases expression	1
1-Naphthylisothiocyanate	affects cotreatment, affects expression	1
Cyclosporine	affects cotreatment, affects expression	1
Medroxyprogesterone Acetate	increases expression	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis