C1Q deficiency 2

Summary

C1Q deficiency 2 (MONDO:0958187) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 32

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	C1Q deficiency 2
Mondo ID	MONDO:0958187
OMIM	620321
UMLS	C5830422
MedGen	1841058
GARD	0026963
Is cancer (heuristic)	no

Data availability: 32 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 2

Related subtypes (2): C1Q deficiency 1, 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

32 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 4 conflicting classifications of pathogenicity, 3 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
440741	NM_001378156.1(C1QB):c.181+1G>T	C1QB	Pathogenic	no assertion criteria provided
17072	NM_001378156.1(C1QB):c.523C>T (p.Arg175Ter)	C1QB	Likely pathogenic	criteria provided, single submitter
3580835	NM_001378156.1(C1QB):c.181+1G>A	C1QB	Likely pathogenic	criteria provided, single submitter
3580849	NM_001378156.1(C1QB):c.262G>A (p.Gly88Ser)	C1QB	Likely pathogenic	criteria provided, single submitter
1483546	NM_001378156.1(C1QB):c.129dup (p.Thr44fs)	C1QB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1934332	NM_001378156.1(C1QB):c.51G>A (p.Leu17=)	C1QB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2231190	NM_001378156.1(C1QB):c.358A>G (p.Ile120Val)	C1QB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626067	NM_001378156.1(C1QB):c.217G>A (p.Gly73Arg)	C1QB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1020369	NM_001378156.1(C1QB):c.61G>A (p.Asp21Asn)	C1QB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1362954	NM_001378156.1(C1QB):c.400C>T (p.Arg134Trp)	C1QB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1435489	NM_001378156.1(C1QB):c.427G>A (p.Val143Met)	C1QB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1443928	NM_001378156.1(C1QB):c.91G>A (p.Gly31Arg)	C1QB	Uncertain significance	criteria provided, multiple submitters, no conflicts
2150388	NM_001378156.1(C1QB):c.388G>A (p.Val130Ile)	C1QB	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431801	NM_001378156.1(C1QB):c.623G>A (p.Gly208Asp)	C1QB	Uncertain significance	criteria provided, single submitter
3580799	NM_001378156.1(C1QB):c.36G>A (p.Met12Ile)	C1QB	Uncertain significance	criteria provided, single submitter
3580803	NM_001378156.1(C1QB):c.46C>T (p.Leu16Phe)	C1QB	Uncertain significance	criteria provided, single submitter
3580815	NM_001378156.1(C1QB):c.89C>G (p.Thr30Ser)	C1QB	Uncertain significance	criteria provided, single submitter
3580824	NM_001378156.1(C1QB):c.95C>A (p.Pro32His)	C1QB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3580831	NM_001378156.1(C1QB):c.134C>G (p.Pro45Arg)	C1QB	Uncertain significance	criteria provided, single submitter
3580837	NM_001378156.1(C1QB):c.203A>G (p.Asp68Gly)	C1QB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3580841	NM_001378156.1(C1QB):c.205C>T (p.His69Tyr)	C1QB	Uncertain significance	criteria provided, single submitter
3580853	NM_001378156.1(C1QB):c.305C>T (p.Pro102Leu)	C1QB	Uncertain significance	criteria provided, single submitter
3580860	NM_001378156.1(C1QB):c.374C>T (p.Thr125Ile)	C1QB	Uncertain significance	criteria provided, single submitter
3580872	NM_001378156.1(C1QB):c.401G>C (p.Arg134Pro)	C1QB	Uncertain significance	criteria provided, single submitter
3580876	NM_001378156.1(C1QB):c.409A>T (p.Thr137Ser)	C1QB	Uncertain significance	criteria provided, single submitter
3580882	NM_001378156.1(C1QB):c.428T>C (p.Val143Ala)	C1QB	Uncertain significance	criteria provided, single submitter
3580885	NM_001378156.1(C1QB):c.434C>A (p.Thr145Asn)	C1QB	Uncertain significance	criteria provided, single submitter
3580888	NM_001378156.1(C1QB):c.449A>G (p.Asn150Ser)	C1QB	Uncertain significance	criteria provided, single submitter
3580895	NM_001378156.1(C1QB):c.461G>A (p.Arg154His)	C1QB	Uncertain significance	criteria provided, single submitter
3580899	NM_001378156.1(C1QB):c.527G>A (p.Gly176Glu)	C1QB	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
C1QB	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
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)
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: 1 · 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	1	1.8×	0.558

Per-gene assignment

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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
decidua	1
right lung	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C1QB	266	broad	marker	right lung, spleen, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C1QB	2,357

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C1QB	P02746	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 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 1 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	1	1903.3×	0.002	C1QB
Initial triggering of complement	1	601.0×	0.002	C1QB
Regulation of Complement cascade	1	233.1×	0.004	C1QB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 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	1	2407.4×	0.002	C1QB
complement activation	1	624.1×	0.002	C1QB
complement activation, classical pathway	1	543.6×	0.002	C1QB
innate immune response	1	33.6×	0.030	C1QB

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
C1QB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	C1QB

Undrugged target profiles

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

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.