C1Q deficiency

Summary

C1Q deficiency (MONDO:0013343) is a disease caused by variants in C1QB, C1QA, and C1QC, with 3 cohort genes. The dominant Reactome pathway is Classical antibody-mediated complement activation (3 cohort genes).

At a glance

• Causal genes: C1QB (GenCC Definitive), C1QA (GenCC Strong), C1QC (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	C1Q deficiency
Mondo ID	MONDO:0013343
OMIM	613652
NCIT	C119990
UMLS	C3150902
MedGen	462252
GARD	0012958
Is cancer (heuristic)	no

Also known as: C1Q deficiency · C1q deficiency · C1QD

Data availability: 23 ClinVar variants · 6 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › complement deficiency › immunodeficiency due to a classical component pathway complement deficiency › C1Q deficiency

Related subtypes (5): complement component C1r/C1s deficiency, complement component 2 deficiency, complement component C1s deficiency, complement component 4b deficiency, complement component 4a deficiency

Subtypes (3): C1Q deficiency 1, C1Q deficiency 2, C1Q deficiency 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

23 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 4 pathogenic, 3 conflicting classifications of pathogenicity, 3 likely pathogenic, 2 benign/likely benign, 1 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1332787	NM_015991.4(C1QA):c.79C>T (p.Arg27Ter)	C1QA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17073	NM_015991.4(C1QA):c.622C>T (p.Gln208Ter)	C1QA	Pathogenic	criteria provided, multiple submitters, no conflicts
440740	NM_015991.4(C1QA):c.648G>A (p.Trp216Ter)	C1QA	Pathogenic	no assertion criteria provided
17070	NM_172369.5(C1QC):c.205C>T (p.Arg69Ter)	C1QC	Pathogenic	criteria provided, single submitter
17071	NM_172369.5(C1QC):c.100G>A (p.Gly34Arg)	C1QC	Pathogenic	criteria provided, multiple submitters, no conflicts
636701	NM_015991.4(C1QA):c.470G>A (p.Gly157Asp)	C1QA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
974838	NM_015991.4(C1QA):c.210delinsAA (p.Gly71fs)	C1QA	Likely pathogenic	criteria provided, single submitter
440742	NM_001378156.1(C1QB):c.724G>A (p.Gly242Arg)	C1QB	Likely pathogenic	criteria provided, single submitter
626067	NM_001378156.1(C1QB):c.217G>A (p.Gly73Arg)	C1QB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1164154	NM_172369.5(C1QC):c.8T>C (p.Val3Ala)	C1QC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
625896	NM_172369.5(C1QC):c.19_20delinsAA (p.Ser7Asn)	C1QC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1444785	NM_015991.4(C1QA):c.162G>A (p.Pro54=)	C1QA	Uncertain significance	criteria provided, multiple submitters, no conflicts
1468526	NM_015991.4(C1QA):c.11C>G (p.Pro4Arg)	C1QA	Uncertain significance	criteria provided, multiple submitters, no conflicts
2249605	NM_001378156.1(C1QB):c.371C>A (p.Ala124Asp)	C1QB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1030316	NM_172369.5(C1QC):c.538G>A (p.Val180Met)	C1QC	Uncertain significance	criteria provided, multiple submitters, no conflicts
1351790	NM_172369.5(C1QC):c.551G>A (p.Arg184His)	C1QC	Uncertain significance	criteria provided, multiple submitters, no conflicts
1675123	NM_172369.5(C1QC):c.706G>A (p.Val236Ile)	C1QC	Uncertain significance	criteria provided, multiple submitters, no conflicts
2501741	NM_172369.5(C1QC):c.19delinsAA (p.Ser7fs)	C1QC	Uncertain significance	criteria provided, single submitter
2584937	NM_172369.5(C1QC):c.644AGG[1] (p.Glu216del)	C1QC	Uncertain significance	criteria provided, single submitter
440743	NM_172369.5(C1QC):c.490G>A (p.Gly164Ser)	C1QC	Uncertain significance	criteria provided, single submitter
1167796	NM_015991.4(C1QA):c.276A>G (p.Gly92=)	C1QA	Benign	criteria provided, multiple submitters, no conflicts
522247	NM_015991.4(C1QA):c.67G>A (p.Glu23Lys)	C1QA	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
522248	NM_001378156.1(C1QB):c.543C>T (p.Asn181=)	C1QB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
C1QB	Definitive	Unknown	C1Q deficiency	2
C1QA	Strong	Autosomal recessive	C1Q deficiency	2
C1QC	Strong	Autosomal recessive	C1Q deficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
C1QA	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency
C1QA	Orphanet:300345	Autosomal systemic lupus erythematosus
C1QB	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency
C1QC	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
C1QA	HGNC:1241	ENSG00000173372	P02745	Complement C1q subcomponent subunit A	gencc,clinvar
C1QB	HGNC:1242	ENSG00000173369	P02746	Complement C1q subcomponent subunit B	gencc,clinvar
C1QC	HGNC:1245	ENSG00000159189	P02747	Complement C1q subcomponent subunit C	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C1QA	Complement C1q subcomponent subunit A	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 t…
C1QB	Complement C1q subcomponent subunit B	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 t…
C1QC	Complement C1q subcomponent subunit C	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 t…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
C1QA	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom
C1QB	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom
C1QC	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
decidua	3
spleen	3
right lung	2
ileal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C1QA	260	broad	marker	spleen, right lung, decidua
C1QB	266	broad	marker	right lung, spleen, decidua
C1QC	237	broad	marker	decidua, spleen, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C1QA	3,182
C1QB	2,357
C1QC	1,899

Intra-cohort edges

A	B	Sources
C1QA	C1QB	intact, string_interaction
C1QA	C1QC	intact, string_interaction
C1QB	C1QC	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C1QA	P02745	11
C1QB	P02746	11
C1QC	P02747	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Classical antibody-mediated complement activation	3	1903.3×	6e-10	C1QA, C1QB, C1QC
Initial triggering of complement	3	601.0×	2e-08	C1QA, C1QB, C1QC
Regulation of Complement cascade	3	233.1×	2e-07	C1QA, C1QB, C1QC
Creation of C4 and C2 activators	2	1268.9×	1e-06	C1QA, C1QC
Complement cascade	2	423.0×	1e-05	C1QA, C1QC
Innate Immune System	2	17.0×	0.006	C1QA, C1QC
Dengue virus activates/modulates innate and adaptive immune responses	1	112.0×	0.010	C1QA
Immune System	2	8.6×	0.017	C1QA, C1QC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
synapse pruning	3	2407.4×	6e-10	C1QA, C1QB, C1QC
complement activation, classical pathway	3	543.6×	4e-08	C1QA, C1QB, C1QC
complement activation	2	416.1×	3e-05	C1QA, C1QB
innate immune response	3	33.6×	9e-05	C1QA, C1QB, C1QC
vertebrate eye-specific patterning	1	1872.4×	0.001	C1QA
complement-mediated synapse pruning	1	1404.3×	0.002	C1QA
negative regulation of granulocyte differentiation	1	702.2×	0.002	C1QC
negative regulation of macrophage differentiation	1	702.2×	0.002	C1QC
neuron remodeling	1	401.2×	0.004	C1QA
astrocyte activation	1	330.4×	0.004	C1QA
microglial cell activation	1	208.1×	0.006	C1QA
synapse organization	1	93.6×	0.012	C1QA
cell-cell signaling	1	23.2×	0.046	C1QA
immune response	1	15.7×	0.062	C1QC

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
C1QA	0	0
C1QB	0	0
C1QC	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	C1QA, C1QB, C1QC

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
C1QA	0	—
C1QB	0	—
C1QC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.