C1QA

Summary

C1QA (complement C1q A chain, HGNC:1241) is a protein-coding gene on chromosome 1p36.12, encoding Complement C1q subcomponent subunit A (P02745). 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 A-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. 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. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 712 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus related to C1QA (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 161 total — 8 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_015991

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1241
Approved symbol	C1QA
Name	complement C1q A chain
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000173372
Ensembl biotype	protein_coding
OMIM	120550
Entrez	712

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 20 protein_coding

ENST00000374642, ENST00000402322, ENST00000438241, ENST00000695738, ENST00000695739, ENST00000695740, ENST00000695741, ENST00000695742, ENST00000695743, ENST00000695744, ENST00000695745, ENST00000695746, ENST00000882020, ENST00000882021, ENST00000882022, ENST00000882023, ENST00000882024, ENST00000882025, ENST00000965381, ENST00000965382

RefSeq mRNA: 3 — MANE Select: NM_015991 NM_001347465, NM_001347466, NM_015991

CCDS: CCDS226

Canonical transcript exons

ENST00000374642 — 3 exons

Exon	Start	End
ENSE00001413929	22636628	22636702
ENSE00003964895	22637610	22637779
ENSE00003964898	22638833	22639678

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 99.43.

FANTOM5 (CAGE): breadth broad, TPM avg 40.8758 / max 4835.5242, expressed in 400 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1286	29.2969	387
1288	5.4995	324
1287	5.4167	314
1285	0.4276	167
1289	0.1971	80
201406	0.0379	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	99.43	gold quality
right lung	UBERON:0002167	99.12	gold quality
decidua	UBERON:0002450	98.93	gold quality
gall bladder	UBERON:0002110	98.85	gold quality
right coronary artery	UBERON:0001625	98.81	gold quality
lymph node	UBERON:0000029	98.34	gold quality
right adrenal gland cortex	UBERON:0035827	98.28	gold quality
upper lobe of left lung	UBERON:0008952	98.25	gold quality
upper lobe of lung	UBERON:0008948	98.22	gold quality
lower lobe of lung	UBERON:0008949	98.22	gold quality
right adrenal gland	UBERON:0001233	97.82	gold quality
mucosa of stomach	UBERON:0001199	97.69	gold quality
left adrenal gland cortex	UBERON:0035825	97.38	gold quality
left adrenal gland	UBERON:0001234	97.34	gold quality
omental fat pad	UBERON:0010414	97.21	gold quality
peritoneum	UBERON:0002358	97.17	gold quality
descending thoracic aorta	UBERON:0002345	97.11	gold quality
adrenal cortex	UBERON:0001235	97.04	gold quality
coronary artery	UBERON:0001621	97.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.01	gold quality
left coronary artery	UBERON:0001626	96.92	gold quality
layer of synovial tissue	UBERON:0007616	96.79	gold quality
pericardium	UBERON:0002407	96.72	gold quality
thoracic aorta	UBERON:0001515	96.71	gold quality
rectum	UBERON:0001052	96.59	gold quality
ascending aorta	UBERON:0001496	96.56	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.53	gold quality
synovial joint	UBERON:0002217	96.47	gold quality
left uterine tube	UBERON:0001303	95.96	gold quality
small intestine	UBERON:0002108	95.95	gold quality

Single-cell (SCXA)

Detected in 42 experiment(s), a significant marker in 42.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	14204.63
E-MTAB-8495	yes	11926.66
E-GEOD-135922	yes	9317.80
E-MTAB-9906	yes	9151.15
E-MTAB-10553	yes	9044.75
E-MTAB-7407	yes	8750.68
E-MTAB-6308	yes	8749.29
E-MTAB-6701	yes	7180.09
E-MTAB-8322	yes	6968.41
E-CURD-122	yes	6916.57
E-HCAD-9	yes	6328.95
E-MTAB-8410	yes	5942.85
E-MTAB-6653	yes	5640.02
E-CURD-98	yes	5621.32
E-HCAD-36	yes	5181.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA1, MAFB, PITX3

miRNA regulators (miRDB)

7 targeting C1QA, 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-6892-3P	99.68	66.40	1178
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980

Literature-anchored findings (GeneRIF, showing 40)

• We report an association between subacute cutaneous lupus erythematosus (SCLE) and a new single nucleotide polymorphism (SNP) in the C1QA gene. We also describe an association between this SNP and lower levels of serum C1q. (PMID:12630757)
• 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 A chain may have evolved as a functionally specialized domain or module with distinct binding properties which together with the B 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 complementary role for Arg162 of the C1q A chain in the C1q-IgG interaction. (PMID:15034050)
• analysis of C-reactive protein binding to FcgammaRI, FcgammaRIIa, and C1q (PMID:15878871)
• fibromodulin activates the classical pathway of complement by directly binding C1q (PMID:16046396)
• These results suggest there could be an association of a single nucleotide polymorphism at position 276 of the C1qA component of complement with breast cancer metastasis to sites linked to hematogenous spread of disease. (PMID:16465510)
• 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)
• Betulin disulphate (B2S) and 9,9-bis(4’-hydroxyphenyl)fluorene disulphate (F2S) inhibit the interaction of C1q and its recombinant globular modules with target molecules IgG1, C-reactive protein (CRP) and long pentraxin 3 (PTX3). (PMID:17929239)
• The dominant types of C1q complexes that circulate in vivo are C1q-C3d and C1q-C4d complexes. (PMID:18054386)
• various conformational isoforms (native, amyloid fibrils, and beta-oligomers) of recombinant human PrP (90-231 and 121-231) bind C1q and activate complement. (PMID:18406463)
• polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma. (PMID:18927313)
• The C1QA gene is associated with subphenotypes of lupus in the African-American and Hispanic subjects. (PMID:19440201)
• Downregulation of C1q enhances prostate hyperplasia and cancerous formation due to failure of WOX1 activation (PMID:19484134)
• C1QA (rs172378)correlates with earlier age of onset in TTR Val30Met familial amyloidotic polyneuropathy. (PMID:19493541)
• M1 blocked the interaction between C1qA and heat-aggregated IgG in vitro and inhibited haemolysis. (PMID:19656971)
• These findings suggest coat protein inhibits C1 and MBL activation via a novel mechanism of interference with the normal interaction of the recognition molecule with its cognate serine proteases. (PMID:19896716)
• Analysis of human C1q by combined bottom-up and top-down mass spectrometry. (PMID:20008834)
• 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)
• rs172378 is linked to a regulatory element affecting gene expression and that allelic preferential expression is altered in tumour samples, but do not support an association between genetic variation in C1QA and breast cancer survival. (PMID:20332777)
• reduced levels of the expression of C1q by dendritic cells and macrophages in the esophagus may play a role in the formation of immune responses associated with the formation of specialized intestinal metaplasia and the development of adenocarcinoma. (PMID:20496011)
• 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 29-month-old boy presented with facial rash and history of early death of a sibling with infections, was found to have a selective deficiency of C1q with a homozygous point mutation in the C1qA gene cahin. (PMID:20560256)
• Results suggest a novel mechanism for pathogen entry into host cells as well as a new function for C1q- alpha2beta1 integrin interactions. (PMID:21134100)
• The presence of anti-globular head fragment in both healthy and diseased humans also implies that these antibodies, unlike anti-collagen-like region, may have a contribution to an onset of autoimmunity. (PMID:21159384)
• Data show that the C1q binding assay could discriminate between different levels of aggregates where ACA had reached a plateau. (PMID:21256764)
• we present evidence suggesting that microglia are capable of phagocytosing and clearing cellular debris of degenerating neurons from the substantia nigra pars compacta through a C1q-mediated pathway (PMID:21343881)
• C1q may induce tolerogenic properties in developing dendritic cells. (PMID:21429584)
• 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)
• There was no association between C1QA rs292001 genetic variants and schizophrenia when compared to healthy subjects. (PMID:21951915)
• A genetic association of the TRAF1/C5, C1q, and eNOS gene polymorphism, but not of STAT4 and PTPN22, was found to confer a degree of risk for systemic lupus erythematosus in the Turkish population. (PMID:21968398)
• The C1qA SNPs, rs172378 and rs665691, confer no genetic predisposition to systemic lupus erythematosus in a Chinese Han population (PMID:22236909)
• C1qA can counteract the function of the C1q receptor gC1qR in RIG-I-mediated signalling (PMID:22260551)
• This study demonstrated that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surfac. (PMID:22356764)
• identification of a new mutation in C1qA that disrupts the start codon (ATG to AGG (Met1Arg)) expands the knowledge and importance of the C1q gene in the pathogenesis of lupus, especially in the high-risk African-American population (PMID:22472776)
• C1q/gC1qR may regulate dendritic cells differentiation and function through the DC-SIGN-mediated induction of cell-signaling pathways. (PMID:22700724)
• We identified a major linear epitope of C1q that is the target of anti-C1q in systemic lupus erythematosis. (PMID:22740328)
• Annexin A2 and A5 serve as new ligands for C1q on apoptotic cells (PMID:22879587)
• The ability of C1q to sense both human and bacterial GAPDHs sheds new insights on the role of this important defense collagen molecule in modulating the immune response. (PMID:23086952)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1qa	ENSDARG00000044613
mus_musculus	C1qa	ENSMUSG00000036887
rattus_norvegicus	C1qa	ENSRNOG00000012807

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), C1QB (ENSG00000173369), C1QTNF1 (ENSG00000173918), ADIPOQ (ENSG00000181092), OTOL1 (ENSG00000182447), C1QTNF8 (ENSG00000184471), C1QL4 (ENSG00000186897), C1QTNF9B (ENSG00000205863), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Complement C1q subcomponent subunit A — P02745 (reviewed: P02745)

All UniProt accessions (8): A0A024RAG6, A0A8Q3SI02, A0A8Q3SI08, A0A8Q3SI41, A0A8Q3SI59, A0A8Q3SI63, P02745, X6RLJ0

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). Interacts with CR1 (via Sushi 24 and Sushi 25 domains). Interacts (via C-terminus) with CD33; this interaction activates CD33 inhibitory motifs. (Microbial infection) Interacts with Staphylococcus aureus protein Cna; this interaction results in the inhibition of the classical complement pathway.

Subcellular location. Secreted. Cell surface.

Post-translational modifications. O-linked glycans are assumed to be the Glc-Gal disaccharides typically found as secondary modifications of hydroxylated lysines in collagen-like domains.

Disease relevance. C1q deficiency 1 (C1QD1) [MIM:613652] 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_001334394, NP_001334395, NP_057075* (*=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 (47 total): strand 13, modified residue 11, glycosylation site 5, sequence conflict 5, domain 2, disulfide bond 2, mutagenesis site 2, signal peptide 1, chain 1, sequence variant 1, turn 1, region of interest 1, compositionally biased region 1, binding site 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-P02745-F1	83.68	0.55

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 (1): 199

Post-translational modifications (11): 48, 54, 57, 67, 73, 79, 85, 100, 33, 39, 45

Disulfide bonds (2): 26, 172–190

Glycosylation sites (5): 33, 48, 67, 100, 146

Mutagenesis-validated functional residues (2):

Position	Phenotype
81	in lysa59; impaired ability to associate with c1r and c1s.
222	decreases binding to igm and igg.

Function

Pathways and Gene Ontology

Reactome pathways

8 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-9920588	Dengue virus activates/modulates innate and adaptive immune responses
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: 306 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, MODULE_92, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MYOGENIN_Q6, HNF3ALPHA_Q6, MCLACHLAN_DENTAL_CARIES_UP, GOBP_INFLAMMATORY_RESPONSE, GOCC_COLLAGEN_TRIMER, REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS, GOBP_NEURON_MATURATION, GOBP_GLIAL_CELL_DEVELOPMENT, GOCC_CELL_SURFACE, AREB6_01, GOBP_NEUROGENESIS

GO Biological Process (12): microglial cell activation (GO:0001774), complement activation (GO:0006956), complement activation, classical pathway (GO:0006958), cell-cell signaling (GO:0007267), neuron remodeling (GO:0016322), innate immune response (GO:0045087), astrocyte activation (GO:0048143), synapse organization (GO:0050808), synapse pruning (GO:0098883), complement-mediated synapse pruning (GO:0150062), vertebrate eye-specific patterning (GO:0150064), immune system process (GO:0002376)

GO Molecular Function (5): amyloid-beta binding (GO:0001540), phosphatidylserine binding (GO:0001786), IgM binding (GO:0001791), IgG binding (GO:0019864), protein binding (GO:0005515)

GO Cellular Component (12): 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), 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-6 pathways:

Category	Pathways
Complement cascade	2
Creation of C4 and C2 activators	1
Dengue Virus-Host Interactions	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	3
glial cell activation	2
immunoglobulin binding	2
extracellular protein-containing complex	2
synapse	2
extrinsic component of synaptic membrane	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
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
cell communication	1
signaling	1
neuron maturation	1
immune response	1
defense response to symbiont	1
astrocyte development	1
cell junction organization	1
synapse organization	1
cell junction disassembly	1
synapse pruning	1
regionalization	1
central nervous system development	1
visual system development	1
biological_process	1
peptide binding	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
presynaptic membrane	1
postsynaptic membrane	1
other organism part	1

Protein interactions and networks

STRING

3068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QA	C1QB	P02746	984
C1QA	C1QC	P02747	984
C1QA	C1S	P09871	845
C1QA	C4A	P01028	822
C1QA	C1R	P00736	820
C1QA	CD93	Q9NPY3	802
C1QA	CFB	P00751	786
C1QA	C5AR1	P21730	783
C1QA	MBL2	P11226	759
C1QA	TYROBP	O43914	755
C1QA	C3AR1	Q16581	753
C1QA	TREM2	Q9NZC2	730
C1QA	CSF1R	P07333	706
C1QA	AIF1	P55008	702
C1QA	C4A	P01028	690

IntAct

45 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	C1QA	psi-mi:“MI:0407”(direct interaction)	0.700
C1QA	C1QBP	psi-mi:“MI:0407”(direct interaction)	0.700
C1QBP	C1QA	psi-mi:“MI:0403”(colocalization)	0.700
C1QA	UBQLN2	psi-mi:“MI:0915”(physical association)	0.670
C1QA	SGTB	psi-mi:“MI:0915”(physical association)	0.560
CD33	C1QA	psi-mi:“MI:0915”(physical association)	0.520
CFHR5	C1QA	psi-mi:“MI:0407”(direct interaction)	0.440
PTX3	C1QA	psi-mi:“MI:0915”(physical association)	0.400
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
HSPB2	C1QA	psi-mi:“MI:0915”(physical association)	0.370
NLGN3	C1QA	psi-mi:“MI:0915”(physical association)	0.370
HMGB1	C1QA	psi-mi:“MI:0915”(physical association)	0.370
C1QA	PIAS2	psi-mi:“MI:0915”(physical association)	0.370
GNPNAT1	C1QA	psi-mi:“MI:0915”(physical association)	0.370
C1QA	SGTA	psi-mi:“MI:0915”(physical association)	0.370
BAG6	C1QA	psi-mi:“MI:0915”(physical association)	0.370
C1QA	UBQLN1	psi-mi:“MI:0915”(physical association)	0.370
C1QA	SLC25A47	psi-mi:“MI:0915”(physical association)	0.370
PPP1CC	C1QA	psi-mi:“MI:0915”(physical association)	0.370
PPP1CA	C1QA	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (69): RAC1 (Affinity Capture-Western), RAC1 (Affinity Capture-Luminescence), C1QA (Two-hybrid), C1QA (Two-hybrid), UBQLN2 (Two-hybrid), SGTB (Two-hybrid), C1QA (Reconstituted Complex), DCN (Reconstituted Complex), C1S (Affinity Capture-Western), C1R (Affinity Capture-Western), FN1 (Reconstituted Complex), C1QA (Two-hybrid), TUBA4A (Affinity Capture-MS), MANBA (Affinity Capture-MS), NPTX1 (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
C1QA	“form complex”	“Complement C1q”	binding
C1QBP	“down-regulates activity”	C1QA	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	3
Uncertain significance	83
Likely benign	60
Benign	3

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1364617	NM_015991.4(C1QA):c.151_152insCGGGTAAGCA (p.Gln51fs)	Pathogenic
17073	NM_015991.4(C1QA):c.622C>T (p.Gln208Ter)	Pathogenic
1969587	NM_015991.4(C1QA):c.209del (p.Gln70fs)	Pathogenic
2025923	NM_015991.4(C1QA):c.129del (p.Arg44fs)	Pathogenic
2421419	NM_015991.4(C1QA):c.577dup (p.Thr193fs)	Pathogenic
2834881	NM_015991.4(C1QA):c.306_307insG (p.Lys103fs)	Pathogenic
3714817	NM_015991.4(C1QA):c.334C>T (p.Gln112Ter)	Pathogenic
440740	NM_015991.4(C1QA):c.648G>A (p.Trp216Ter)	Pathogenic
1215669	NM_015991.4(C1QA):c.469G>T (p.Gly157Cys)	Likely pathogenic
636701	NM_015991.4(C1QA):c.470G>A (p.Gly157Asp)	Likely pathogenic
974838	NM_015991.4(C1QA):c.210delinsAA (p.Gly71fs)	Likely pathogenic

SpliceAI

749 predictions. Top by Δscore:

Variant	Effect	Δscore
1:22637726:G:GT	donor_gain	1.0000
1:22638827:CCACA:C	acceptor_loss	1.0000
1:22638828:CACAG:C	acceptor_loss	1.0000
1:22638829:ACAGG:A	acceptor_gain	1.0000
1:22638830:CA:C	acceptor_loss	1.0000
1:22638831:A:AG	acceptor_gain	1.0000
1:22638831:A:G	acceptor_loss	1.0000
1:22638831:AGG:A	acceptor_gain	1.0000
1:22638831:AGGG:A	acceptor_gain	1.0000
1:22638832:G:GA	acceptor_loss	1.0000
1:22638832:G:GG	acceptor_gain	1.0000
1:22638832:GGG:G	acceptor_gain	1.0000
1:22638832:GGGG:G	acceptor_gain	1.0000
1:22638832:GGGGC:G	acceptor_gain	1.0000
1:22637608:A:AG	acceptor_gain	0.9900
1:22637609:G:GG	acceptor_gain	0.9900
1:22637609:GA:G	acceptor_gain	0.9900
1:22637609:GAGGC:G	acceptor_gain	0.9900
1:22637709:G:GT	donor_gain	0.9900
1:22637709:G:T	donor_gain	0.9900
1:22637718:G:T	donor_gain	0.9900
1:22638829:A:AG	acceptor_gain	0.9900
1:22638829:ACAG:A	acceptor_gain	0.9900
1:22638831:AG:A	acceptor_gain	0.9900
1:22638832:GG:G	acceptor_gain	0.9900
1:22637604:CCACA:C	acceptor_loss	0.9800
1:22637605:CACA:C	acceptor_loss	0.9800
1:22637606:ACAG:A	acceptor_loss	0.9800
1:22637608:AG:A	acceptor_loss	0.9800
1:22637608:AGAG:A	acceptor_gain	0.9800

AlphaMissense

1567 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:22639018:T:C	F117L	0.994
1:22639020:C:A	F117L	0.994
1:22639020:C:G	F117L	0.994
1:22639066:T:C	F133L	0.992
1:22639068:C:A	F133L	0.992
1:22639068:C:G	F133L	0.992
1:22639019:T:G	F117C	0.991
1:22639019:T:C	F117S	0.989
1:22639067:T:G	F133C	0.989
1:22639151:T:C	F161S	0.988
1:22639120:T:C	F151L	0.987
1:22639121:T:G	F151C	0.987
1:22639122:C:A	F151L	0.987
1:22639122:C:G	F151L	0.987
1:22639384:T:C	F239L	0.987
1:22639386:C:A	F239L	0.987
1:22639386:C:G	F239L	0.987
1:22639376:T:C	F236S	0.985
1:22639128:C:G	C153W	0.984
1:22639024:G:C	A119P	0.981
1:22639121:T:C	F151S	0.980
1:22639067:T:C	F133S	0.979
1:22639150:T:C	F161L	0.979
1:22639152:C:A	F161L	0.979
1:22639152:C:G	F161L	0.979
1:22639369:A:C	S234R	0.978
1:22639371:C:A	S234R	0.978
1:22639371:C:G	S234R	0.978
1:22639376:T:G	F236C	0.978
1:22639382:G:A	G238D	0.978

dbSNP variants (sampled 300 via entrez): RS1002520235 (1:22637266 A>T), RS1002672995 (1:22639059 G>A,C), RS1003138233 (1:22639443 G>A), RS1004719999 (1:22636753 G>A), RS1004772191 (1:22636425 C>T), RS1005389641 (1:22639786 C>T), RS1006015434 (1:22636221 G>A,T), RS1006393868 (1:22638446 G>T), RS1006443157 (1:22638058 G>A), RS1006608432 (1:22640139 C>T), RS1007071868 (1:22639907 G>A), RS1007616758 (1:22638763 G>A,C,T), RS1008101886 (1:22634874 C>T), RS1008245346 (1:22638404 A>G), RS1008445524 (1:22635162 G>A)

Disease associations

OMIM: gene MIM:120550 | disease phenotypes: MIM:613652

GenCC curated gene-disease

Disease	Classification	Inheritance
C1Q deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
systemic lupus erythematosus related to C1QA	Definitive	AR

Mondo (2): C1Q deficiency (MONDO:0013343), C1Q deficiency 1 (MONDO:0958182)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000793	Membranoproliferative glomerulonephritis
HP:0002719	Recurrent infections
HP:0002725	Systemic lupus erythematosus
HP:0002960	Autoimmunity
HP:0005356	Decreased circulating complement factor I concentration

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90000584_1	Inflammatory biomarkers (multivariate analysis)	1.000000e-73

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004872	inflammatory biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
peroben	affects binding, increases activity	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
nickel sulfate	decreases expression	1
monomethylpropion	increases expression	1
di-n-butylphosphoric acid	affects expression	1
lipopolysaccharide, E coli O55-B5	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Allergens	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	increases methylation	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.