C1QBP

complement C1q binding protein

Basic information

Region (hg38): 17:5432776-5448830

Previous symbols: [ "HABP1" ]

Links

ENSG00000108561 ∙ NCBI:708 ∙ OMIM:601269 ∙ HGNC:1243 ∙ Uniprot:Q07021 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation deficiency 33 (Strong), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 33 (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 33	AR	Cardiovascular	Among other features, individuals have been described as manifesting with cardiomyopahty, and awareness may allow early diagnosis and management	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Renal	28942965

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C1QBP gene.

• not provided (102 variants)
• Inborn genetic diseases (11 variants)
• Combined oxidative phosphorylation deficiency 33 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C1QBP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	32	2	35
missense		1	37	4	3	45
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel			3			3
splice donor/acceptor (+/-2bp)			1			1
splice region			4	5	1	10
non coding			1	3	10	14
Total	2	1	43	39	15

Variants in C1QBP

This is a list of pathogenic ClinVar variants found in the C1QBP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-5432868-A-G			Benign (May 10, 2021)
17-5432890-T-C			Benign (May 10, 2021)
17-5432895-A-AT			Benign (May 16, 2021)
17-5433021-G-C		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
17-5433026-T-G			Uncertain significance (May 25, 2022)
17-5433037-T-C		Inborn genetic diseases	Uncertain significance (May 17, 2023)
17-5433040-A-G		Combined oxidative phosphorylation deficiency 33	Pathogenic (Aug 16, 2018)
17-5433041-G-A		Combined oxidative phosphorylation deficiency 33	Pathogenic (Aug 16, 2018)
17-5433059-T-C		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
17-5433072-C-T			Likely benign (Nov 28, 2022)
17-5433077-G-A			Likely benign (Dec 13, 2022)
17-5433077-G-C			Uncertain significance (Jun 16, 2022)
17-5433102-A-G			Likely benign (Aug 17, 2022)
17-5433111-A-G			Likely benign (Dec 13, 2022)
17-5433125-C-A		Combined oxidative phosphorylation deficiency 33	Pathogenic (Oct 12, 2017)
17-5433128-G-A			Pathogenic (Jul 02, 2021)
17-5433131-C-T		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
17-5433132-G-A			Likely benign (Sep 20, 2022)
17-5433147-T-C			Benign (Nov 19, 2023)
17-5433170-A-G			Likely benign (Dec 08, 2023)
17-5433172-G-T		C1QBP-related disorder	Benign/Likely benign (Jan 29, 2024)
17-5433184-C-T			Likely benign (Nov 14, 2023)
17-5433274-C-A			Benign (Jan 29, 2024)
17-5433276-C-A			Likely benign (May 13, 2023)
17-5433289-T-G			Uncertain significance (Oct 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C1QBP	protein_coding	protein_coding	ENST00000225698	6	16054

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.02e-7	0.267	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.06	105	140	0.748	0.00000678	1822
Missense in Polyphen		26	38.245	0.67982		483
Synonymous	-0.452	65	60.5	1.07	0.00000330	564
Loss of Function	0.359	11	12.4	0.890	6.09e-7	145

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.000326	0.000326
South Asian	0.000100	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Is believed to be a multifunctional and multicompartmental protein involved in inflammation and infection processes, ribosome biogenesis, protein synthesis in mitochondria, regulation of apoptosis, transcriptional regulation and pre-mRNA splicing. At the cell surface is thought to act as an endothelial receptor for plasma proteins of the complement and kallikrein- kinin cascades. Putative receptor for C1q; specifically binds to the globular "heads" of C1q thus inhibiting C1; may perform the receptor function through a complex with C1qR/CD93. In complex with cytokeratin-1/KRT1 is a high affinity receptor for kininogen- 1/HMWK. Can also bind other plasma proteins, such as coagulation factor XII leading to its autoactivation. May function to bind initially fluid kininogen-1 to the cell membrane. The secreted form may enhance both extrinsic and intrinsic coagulation pathways. It is postulated that the cell surface form requires docking with transmembrane proteins for downstream signaling which might be specific for a cell-type or response. By acting as C1q receptor is involved in chemotaxis of immature dendritic cells and neutrophils and is proposed to signal through CD209/DC-SIGN on immature dendritic cells, through integrin alpha-4/beta-1 during trophoblast invasion of the decidua, and through integrin beta-1 during endothelial cell adhesion and spreading. Signaling involved in inhibition of innate immune response is implicating the PI3K- AKT/PKB pathway. Required for protein synthesis in mitochondria (PubMed:28942965). In mitochondrial translation may be involved in formation of functional 55S mitoribosomes; the function seems to involve its RNA-binding activity. May be involved in the nucleolar ribosome maturation process; the function may involve the exchange of FBL for RRP1 in the association with pre-ribosome particles. Involved in regulation of RNA splicing by inhibiting the RNA- binding capacity of SRSF1 and its phosphorylation. Is required for the nuclear translocation of splicing factor U2AF1L4. Involved in regulation of CDKN2A- and HRK-mediated apoptosis. Stabilizes mitochondrial CDKN2A isoform smARF. May be involved in regulation of FOXC1 transcriptional activity and NFY/CCAAT-binding factor complex-mediated transcription. May play a role in antibacterial defense as it can bind to cell surface hyaluronan and inhibit Streptococcus pneumoniae hyaluronate lyase. May be involved in modulation of the immune response; ligation by HCV core protein is resulting in suppression of interleukin-12 production in monocyte- derived dendritic cells. Involved in regulation of antiviral response by inhibiting DDX58- and IFIH1-mediated signaling pathways probably involving its association with MAVS after viral infection. {ECO:0000269|PubMed:10022843, ECO:0000269|PubMed:10479529, ECO:0000269|PubMed:10722602, ECO:0000269|PubMed:11086025, ECO:0000269|PubMed:11859136, ECO:0000269|PubMed:15243141, ECO:0000269|PubMed:16140380, ECO:0000269|PubMed:16177118, ECO:0000269|PubMed:17881511, ECO:0000269|PubMed:18676636, ECO:0000269|PubMed:19004836, ECO:0000269|PubMed:19164550, ECO:0000269|PubMed:20810993, ECO:0000269|PubMed:21536856, ECO:0000269|PubMed:21544310, ECO:0000269|PubMed:22700724, ECO:0000269|PubMed:28942965, ECO:0000269|PubMed:8662673, ECO:0000269|PubMed:8710908, ECO:0000269|PubMed:9461517}.; FUNCTION: (Microbial infection) In infection processes acts as an attachment site for microbial proteins, including Listeria monocytogenes internalin B and Staphylococcus aureus protein A. {ECO:0000269|PubMed:10722602, ECO:0000269|PubMed:10747014}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 33 (COXPD33) [MIM:617713]: An autosomal recessive disorder caused by multiple mitochondrial respiratory chain defects and impaired mitochondrial energy metabolism. Clinical manifestations are highly variable. Affected infants present with cardiomyopathy accompanied by multisystemic features involving liver, kidney, and brain. Death in infancy is observed in some patients. Children and adults present with myopathy and progressive external ophthalmoplegia. {ECO:0000269|PubMed:28942965}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Herpes simplex infection - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Human Complement System;Mesodermal Commitment Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Intrinsic Pathway of Fibrin Clot Formation;Hemostasis;Formation of Fibrin Clot (Clotting Cascade) (Consensus)

Recessive Scores

• pRec: 0.957

Intolerance Scores

• loftool: 0.273
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

• pHI: 0.750
• hipred: N
• hipred_score: 0.440
• ghis: 0.640

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.863

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: C1qbp
• Phenotype: cellular phenotype; growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; embryo phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;mRNA processing;apoptotic process;immune response;complement activation, classical pathway;blood coagulation, intrinsic pathway;RNA splicing;phosphatidylinositol 3-kinase signaling;viral process;regulation of complement activation;negative regulation of interferon-gamma production;negative regulation of interleukin-12 production;negative regulation of MDA-5 signaling pathway;negative regulation of RIG-I signaling pathway;mature ribosome assembly;positive regulation of apoptotic process;innate immune response;positive regulation of cell adhesion;negative regulation of mRNA splicing, via spliceosome;negative regulation of defense response to virus;positive regulation of protein kinase B signaling;positive regulation of mitochondrial translation;positive regulation of neutrophil chemotaxis;positive regulation of substrate adhesion-dependent cell spreading;positive regulation of trophoblast cell migration;positive regulation of dendritic cell chemotaxis
• Cellular component: extracellular space;nucleus;nucleolus;cytoplasm;mitochondrion;mitochondrial matrix;cytosol;plasma membrane;cell surface;membrane;presynaptic active zone;glutamatergic synapse;GABA-ergic synapse
• Molecular function: complement component C1q binding;transcription corepressor activity;mRNA binding;protein kinase C binding;protein binding;hyaluronic acid binding;transcription factor binding;translation activator activity;kininogen binding;adrenergic receptor binding;mitochondrial ribosome binding