C1Q deficiency 1

Summary

C1Q deficiency 1 (MONDO:0958182) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	C1Q deficiency 1
Mondo ID	MONDO:0958182
OMIM	613652
GARD	0026959
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

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 › C1Q deficiency 1

Related subtypes (2): 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

3 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4685007	NM_001378156.1(C1QB):c.174del (p.Glu59fs)	C1QB	Pathogenic	criteria provided, single submitter
636701	NM_015991.4(C1QA):c.470G>A (p.Gly157Asp)	C1QA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4071526	NM_015991.4(C1QA):c.159G>T (p.Glu53Asp)	C1QA	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
C1QA	HGNC:1241	ENSG00000173372	P02745	Complement C1q subcomponent subunit A	clinvar
C1QB	HGNC:1242	ENSG00000173369	P02746	Complement C1q subcomponent subunit B	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…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

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

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
decidua	2
right lung	2
spleen	2

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

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C1QA	3,182
C1QB	2,357

Intra-cohort edges

A	B	Sources
C1QA	C1QB	intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C1QA	P02745	11
C1QB	P02746	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 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	2	1903.3×	2e-06	C1QA, C1QB
Initial triggering of complement	2	601.0×	1e-05	C1QA, C1QB
Regulation of Complement cascade	2	233.1×	5e-05	C1QA, C1QB
Creation of C4 and C2 activators	1	951.7×	0.002	C1QA
Complement cascade	1	317.2×	0.005	C1QA
Dengue virus activates/modulates innate and adaptive immune responses	1	167.9×	0.008	C1QA
Innate Immune System	1	12.8×	0.088	C1QA
Immune System	1	6.5×	0.148	C1QA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	2	2407.4×	2e-06	C1QA, C1QB
complement activation	2	624.1×	1e-05	C1QA, C1QB
complement activation, classical pathway	2	543.6×	1e-05	C1QA, C1QB
vertebrate eye-specific patterning	1	2808.7×	1e-03	C1QA
complement-mediated synapse pruning	1	2106.5×	0.001	C1QA
innate immune response	2	33.6×	0.002	C1QA, C1QB
neuron remodeling	1	601.9×	0.003	C1QA
astrocyte activation	1	495.6×	0.003	C1QA
microglial cell activation	1	312.1×	0.004	C1QA
synapse organization	1	140.4×	0.008	C1QA
cell-cell signaling	1	34.8×	0.029	C1QA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	C1QA, C1QB

Undrugged target profiles

2 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	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.