C1QC

Summary

C1QC (complement C1q C chain, HGNC:1245) is a protein-coding gene on chromosome 1p36.12, encoding Complement C1q subcomponent subunit C (P02747). 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 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.

Source: NCBI Gene 714 — RefSeq curated summary.

At a glance

• Gene–disease (curated): C1Q deficiency (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 178 total — 2 pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_172369

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1245
Approved symbol	C1QC
Name	complement C1q C chain
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000159189
Ensembl biotype	protein_coding
OMIM	120575
Entrez	714

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000374637, ENST00000374639, ENST00000374640, ENST00000695749, ENST00000695750, ENST00000695751, ENST00000695752, ENST00000695753, ENST00000867664, ENST00000867665, ENST00000968848

RefSeq mRNA: 4 — MANE Select: NM_172369 NM_001114101, NM_001347619, NM_001347620, NM_172369

CCDS: CCDS227, CCDS90877

Canonical transcript exons

ENST00000374640 — 3 exons

Exon	Start	End
ENSE00001464106	22644011	22644204
ENSE00003964915	22647227	22648108
ENSE00003964919	22643633	22643714

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 99.54.

FANTOM5 (CAGE): breadth broad, TPM avg 53.2190 / max 8504.9069, expressed in 374 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1293	52.7904	374
1295	0.2159	88
1294	0.1068	31
1296	0.1059	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.54	gold quality
spleen	UBERON:0002106	99.24	gold quality
ileal mucosa	UBERON:0000331	99.22	gold quality
lower lobe of lung	UBERON:0008949	99.17	gold quality
right coronary artery	UBERON:0001625	98.71	gold quality
pericardium	UBERON:0002407	98.69	gold quality
gall bladder	UBERON:0002110	98.66	gold quality
right lung	UBERON:0002167	98.58	gold quality
lymph node	UBERON:0000029	98.44	gold quality
right adrenal gland cortex	UBERON:0035827	98.35	gold quality
vermiform appendix	UBERON:0001154	98.23	gold quality
right adrenal gland	UBERON:0001233	97.85	gold quality
trigeminal ganglion	UBERON:0001675	97.79	gold quality
synovial joint	UBERON:0002217	97.48	gold quality
left adrenal gland cortex	UBERON:0035825	97.39	gold quality
left adrenal gland	UBERON:0001234	97.32	gold quality
adrenal cortex	UBERON:0001235	97.30	gold quality
inferior vagus X ganglion	UBERON:0005363	97.28	gold quality
left ventricle myocardium	UBERON:0006566	97.28	gold quality
mucosa of stomach	UBERON:0001199	97.27	gold quality
upper lobe of lung	UBERON:0008948	97.24	gold quality
upper lobe of left lung	UBERON:0008952	97.13	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.02	gold quality
descending thoracic aorta	UBERON:0002345	97.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.98	gold quality
coronary artery	UBERON:0001621	96.76	gold quality
layer of synovial tissue	UBERON:0007616	96.65	gold quality
left coronary artery	UBERON:0001626	96.61	gold quality
omental fat pad	UBERON:0010414	96.31	gold quality
peritoneum	UBERON:0002358	96.28	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	8491.09
E-MTAB-9906	yes	6925.64
E-MTAB-7407	yes	6839.16
E-GEOD-135922	yes	6003.90
E-MTAB-6701	yes	5115.16
E-HCAD-15	yes	5057.36
E-MTAB-6308	yes	4842.77
E-MTAB-10553	yes	4201.79
E-MTAB-8322	yes	3503.11
E-MTAB-8495	yes	3445.98
E-CURD-98	yes	3099.78
E-HCAD-1	yes	2998.13
E-MTAB-10042	yes	2818.18
E-MTAB-8410	yes	2779.50
E-MTAB-6678	yes	2754.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting C1QC, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-6769A-5P	97.99	64.16	851
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-601	95.98	67.59	421

Literature-anchored findings (GeneRIF, showing 29)

• 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 C chain may have evolved as a functionally specialized domain or module with distinct binding properties which together with the A and B 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 complementary role for Arg156 of C1Q C chain in the C1q-IgG interaction. (PMID:15034050)
• 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)
• C1q polymorphisms are associated with SLE, serum C1q and CH50 levels in a stable founder population of patients with SLE. (PMID:18504288)
• The peripheral globular region of the C1q molecule displays a lectin-like activity, which contributes to DNA binding through interaction with its deoxy-d-ribose moiety and may participate in apoptotic cell recognition. (PMID:18703056)
• Complement C1q chemoattracts human dendritic cells and enhances migration of mature dendritic cells to CCL19 via activation of AKT and MAPK pathways.( (PMID:18838169)
• Complement protein C1q and anti-hexon antibodies together can mediate efficient adenovirus infection in coxsackie and adenovirus receptor-negative cell types. (PMID:19115936)
• C1QC (rs9434) correlates with later age of onset in TTR Val30Met familial amyloidotic polyneuropathy. C1QC (rs15940) does not. (PMID:19493541)
• prevents monocyte-derived dendritic cell differentiation (PMID:19710097)
• C1q deficiency is such a strong risk factor for systemic lupus erythematosus. (PMID:19790049)
• 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)
• Three single nucleotide polymorphisms (STAT6 rs703817, C1qG rs17433222, and MBP rs3794845) were found to be significantly associated with childhood leukemia risk in Koreans. (PMID:20438785)
• 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)
• These results suggest a novel pathway in which C1q and MBL influence removal and metabolism of atherogenic forms of LDL in the early stages of atherosclerosis. (PMID:20833838)
• 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)
• C1q and C1q receptor interaction may be responsible for the C1q-mediated migration of mesenchymal stromal cells. (PMID:22264191)
• 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)
• C1q deficiency due to a Gly164Ser mutation may have a role in Rothmund-Thomson syndrome and glomerulonephritis [case report] (PMID:24157463)
• Neuromyelitis optica patients had higher levels of C3a and anti-C1q antibodies than healthy controls. (PMID:25109258)
• C1QA was associated with later onset, whereas C1QC may have a double role: variants may confer earlier or later age-at-onset (PMID:31019999)
• 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)
• Complement C1QC as a potential prognostic marker and therapeutic target in colon carcinoma based on single-cell RNA sequencing and immunohistochemical analysis. (PMID:35765947)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1qc	ENSDARG00000095627
mus_musculus	C1qc	ENSMUSG00000036896
rattus_norvegicus	C1qc	ENSRNOG00000012804

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), COL8A2 (ENSG00000171812), C1QTNF4 (ENSG00000172247), C1QB (ENSG00000173369), 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 C — P02747 (reviewed: P02747)

All UniProt accessions (5): A0A024RAA7, A0A8Q3SIZ0, A0A8Q3WKR2, A0A8Q3WKR6, P02747

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. O-linked glycans consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups.

Disease relevance. C1q deficiency 3 (C1QD3) [MIM:620322] 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 (4): NP_001107573, NP_001334548, NP_001334549, NP_758957* (*=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 12, sequence conflict 12, strand 10, mutagenesis site 3, domain 2, disulfide bond 2, compositionally biased region 2, signal peptide 1, chain 1, glycosylation site 1, sequence variant 1, helix 1, region of interest 1, turn 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-P02747-F1	81.69	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.

Post-translational modifications (12): 45, 54, 63, 75, 81, 93, 96, 99, 105, 36, 39, 42

Disulfide bonds (2): 32, 179–193

Glycosylation sites (1): 75

Mutagenesis-validated functional residues (3):

Position	Phenotype
86	in lysc58; impaired ability to associate with c1r and c1s.
129	has no effect on binding to igm.
198	decreases binding to igm.

Function

Pathways and Gene Ontology

Reactome pathways

7 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
R-HSA-166658	Complement cascade
R-HSA-166786	Creation of C4 and C2 activators
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 284 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_COLLAGEN_TRIMER, REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS, GOCC_CELL_SURFACE, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_COMPLEMENT_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (7): immune response (GO:0006955), complement activation, classical pathway (GO:0006958), negative regulation of granulocyte differentiation (GO:0030853), innate immune response (GO:0045087), negative regulation of macrophage differentiation (GO:0045650), synapse pruning (GO:0098883), immune system process (GO:0002376)

GO Molecular Function (4): phosphatidylserine binding (GO:0001786), IgM binding (GO:0001791), IgG binding (GO:0019864), protein binding (GO:0005515)

GO Cellular Component (14): extracellular region (GO:0005576), collagen trimer (GO:0005581), complement component C1 complex (GO:0005602), obsolete extracellular space (GO:0005615), cell surface (GO:0009986), extracellular matrix (GO:0031012), synapse (GO:0045202), complement component C1q complex (GO:0062167), blood microparticle (GO:0072562), postsynapse (GO:0098794), extrinsic component of presynaptic membrane (GO:0098888), extrinsic component of postsynaptic membrane (GO:0098890), glutamatergic synapse (GO:0098978), symbiont cell surface (GO:0106139)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Complement cascade	2
Creation of C4 and C2 activators	1
Innate Immune System	1
Initial triggering of complement	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of myeloid leukocyte differentiation	2
immunoglobulin binding	2
extracellular protein-containing complex	2
synapse	2
extrinsic component of synaptic membrane	2
immune system process	1
response to stimulus	1
humoral immune response mediated by circulating immunoglobulin	1
complement activation	1
granulocyte differentiation	1
regulation of granulocyte differentiation	1
immune response	1
defense response to symbiont	1
macrophage differentiation	1
regulation of macrophage differentiation	1
synapse organization	1
cell junction disassembly	1
biological_process	1
phospholipid binding	1
anion binding	1
modified amino acid binding	1
binding	1
protein-containing complex	1
complement component C1q complex	1
external encapsulating structure	1
cell junction	1
extracellular region	1
presynaptic membrane	1
postsynaptic membrane	1
other organism part	1

Protein interactions and networks

STRING

1830 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QC	C1QA	P02745	984
C1QC	C1QB	P02746	983
C1QC	C1R	P00736	933
C1QC	C1S	P09871	920
C1QC	C4A	P01028	701
C1QC	C4A	P01028	640
C1QC	APOE	P02649	602
C1QC	CSF1R	P07333	587
C1QC	AIF1	P55008	561
C1QC	C3	P01024	550
C1QC	PTX3	P26022	547
C1QC	CLU	P10909	524
C1QC	C3AR1	Q16581	513
C1QC	CCR1	P32246	494
C1QC	MASP2	O00187	483

IntAct

39 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
TM2D3	TXNDC12	psi-mi:“MI:0914”(association)	0.640
C1QBP	C1QC	psi-mi:“MI:0407”(direct interaction)	0.580
C1QC	C1QBP	psi-mi:“MI:0407”(direct interaction)	0.580
C1QBP	C1QC	psi-mi:“MI:0403”(colocalization)	0.580
C1QC	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
C1QC	ZNF534	psi-mi:“MI:0915”(physical association)	0.560
CD33	C1QA	psi-mi:“MI:0915”(physical association)	0.520
C1QC	C1QC	psi-mi:“MI:0407”(direct interaction)	0.440
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
C1QC	PTS	psi-mi:“MI:0915”(physical association)	0.370
C1QC	TFAP2A	psi-mi:“MI:0915”(physical association)	0.370
APOA1	CNMD	psi-mi:“MI:0914”(association)	0.350
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
F13B	A2M	psi-mi:“MI:0914”(association)	0.350
S	IGLL5	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
SCRIB	CHD2	psi-mi:“MI:0914”(association)	0.350
C1QC	C1QL1	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
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
RHBDD1	A2ML1	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): UBQLN2 (Two-hybrid), ZNF534 (Two-hybrid), PDP1 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), COL6A1 (Affinity Capture-MS), USP30 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), COL5A1 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL2A1 (Affinity Capture-MS), CCNB1 (Affinity Capture-MS), BANP (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), HYOU1 (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, P02747, P08125, P0C862, P14106, P14282, P23206, P25067, P25318, P27658, P31720, P31721, P31722, P83371, P98085, P98086, Q00780, Q02105, Q03692, Q05306, Q05A80, Q06575, Q06576, Q0II24, Q15848, Q2KIV9, Q2KIX7, Q3Y5Z3, Q4ZJM7, Q4ZJM9, Q4ZJN1, Q5E9E3, Q5FVH0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
C1QC	“form complex”	“Complement C1q”	binding
C1QBP	“down-regulates activity”	C1QC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	76
Likely benign	79
Benign	12

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
17070	NM_172369.5(C1QC):c.205C>T (p.Arg69Ter)	Pathogenic
17071	NM_172369.5(C1QC):c.100G>A (p.Gly34Arg)	Pathogenic

SpliceAI

358 predictions. Top by Δscore:

Variant	Effect	Δscore
1:22644009:A:AG	acceptor_gain	0.9900
1:22644010:G:GG	acceptor_gain	0.9900
1:22644010:GTTCC:G	acceptor_gain	0.9900
1:22647222:TCCA:T	acceptor_loss	0.9900
1:22647224:CAG:C	acceptor_loss	0.9900
1:22647226:G:A	acceptor_loss	0.9900
1:22644007:CCAGT:C	acceptor_loss	0.9800
1:22644008:CAGTT:C	acceptor_loss	0.9800
1:22644010:GTT:G	acceptor_gain	0.9800
1:22644010:GTTC:G	acceptor_gain	0.9800
1:22644200:GCCAG:G	donor_gain	0.9800
1:22644201:CCAG:C	donor_loss	0.9800
1:22644205:GTG:G	donor_loss	0.9800
1:22644206:T:G	donor_loss	0.9800
1:22647220:T:G	acceptor_gain	0.9800
1:22647225:A:AG	acceptor_gain	0.9800
1:22647226:G:GG	acceptor_gain	0.9800
1:22647226:GGA:G	acceptor_gain	0.9800
1:22647219:A:AG	acceptor_gain	0.9700
1:22647225:AG:A	acceptor_gain	0.9700
1:22647226:GG:G	acceptor_gain	0.9700
1:22644010:GT:G	acceptor_gain	0.9600
1:22644161:G:T	donor_gain	0.9600
1:22644205:G:GG	donor_gain	0.9500
1:22643713:AGGTG:A	donor_loss	0.9400
1:22643714:GG:G	donor_loss	0.9400
1:22643715:GTGAG:G	donor_loss	0.9400
1:22646986:G:T	donor_gain	0.9400
1:22647226:GGAAT:G	acceptor_gain	0.9400
1:22643717:G:GT	donor_loss	0.9300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000071806 (1:22642776 C>A,T), RS1000735542 (1:22645185 C>T), RS1000742008 (1:22643023 G>A), RS1001879721 (1:22647919 C>T), RS1002132450 (1:22646152 G>A), RS1002478614 (1:22644700 C>A,G,T), RS1002522936 (1:22643270 C>T), RS1003415069 (1:22641852 G>A), RS1003478565 (1:22648073 T>G), RS1005042302 (1:22642143 G>A), RS1005727858 (1:22644497 C>A), RS1005871828 (1:22647945 T>A,C,G), RS1006551987 (1:22645458 T>G), RS1006583116 (1:22645106 G>A), RS1006819802 (1:22648056 T>C)

Disease associations

OMIM: gene MIM:120575 | disease phenotypes: MIM:613652, MIM:620322

GenCC curated gene-disease

Disease	Classification	Inheritance
C1Q deficiency	Strong	Autosomal recessive

Mondo (2): C1Q deficiency (MONDO:0013343), C1Q deficiency 3 (MONDO:0958188)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003493	Antinuclear antibody positivity
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0007274	Recurrent bacterial meningitis
HP:0007417	Discoid lupus rash
HP:0011463	Childhood onset
HP:0032435	Neonatal omphalitis
HP:0034601	Decreased circulating C1q concentration

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_1810	Blood protein levels	2.000000e-78

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
2,4,6-tribromophenol	decreases expression	1
peroben	increases activity, affects binding	1
tetrabromobisphenol A	decreases expression	1
nickel sulfate	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	affects binding	1
Calcitriol	decreases expression	1
Copper	affects binding	1
Naled	affects expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	increases methylation	1
Zinc	affects binding	1
Aflatoxin B1	decreases methylation	1
Medroxyprogesterone Acetate	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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