Immunodeficiency due to ficolin3 deficiency

Summary

Immunodeficiency due to ficolin3 deficiency (MONDO:0013467) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		1	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency due to ficolin3 deficiency
Mondo ID	MONDO:0013467
OMIM	613860
Orphanet	331190
SNOMED CT	766705006
UMLS	C3151226
MedGen	462576
GARD	0017513
Is cancer (heuristic)	no

Data availability: 11 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › complement deficiency › disorder of lectin complement activation pathway › immunodeficiency due to ficolin3 deficiency

Related subtypes (2): immunodeficiency due to MASP-2 deficiency, mannose-binding lectin deficiency

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

11 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 2 likely pathogenic, 1 likely benign, 1 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3336683	NM_003665.4(FCN3):c.381_382insA (p.Gly128fs)	FCN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4813073	NM_003665.4(FCN3):c.219del (p.Lys74fs)	FCN3	Likely pathogenic	criteria provided, single submitter
4845898	NM_003665.4(FCN3):c.74_77dup (p.His26fs)	FCN3	Likely pathogenic	criteria provided, single submitter
1030693	NM_003665.4(FCN3):c.620A>G (p.Tyr207Cys)	FCN3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441402	NM_003665.4(FCN3):c.797G>A (p.Arg266His)	FCN3	Uncertain significance	criteria provided, single submitter
2441403	NM_003665.4(FCN3):c.440G>T (p.Trp147Leu)	FCN3	Uncertain significance	criteria provided, single submitter
2464933	NM_003665.4(FCN3):c.142G>A (p.Gly48Arg)	FCN3	Uncertain significance	criteria provided, multiple submitters, no conflicts
5285	NM_003665.4(FCN3):c.349del (p.Leu117fs)	FCN3	Uncertain significance	criteria provided, multiple submitters, no conflicts
984510	NM_003665.4(FCN3):c.232+1G>A	FCN3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1285028	NM_003665.4(FCN3):c.498G>C (p.Glu166Asp)	FCN3	Likely benign	criteria provided, single submitter
710189	NM_003665.4(FCN3):c.750C>T (p.His250=)	FCN3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
FCN3	Moderate	Autosomal recessive	immunodeficiency due to ficolin3 deficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FCN3	Orphanet:331190	Immunodeficiency due to ficolin3 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
FCN3	HGNC:3625	ENSG00000142748	O75636	Ficolin-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FCN3	Ficolin-3	Calcium-dependent lectin, which acts as a pattern recognition receptor that initiates the lectin 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)
FCN3	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_C_1, Fibrinogen_CS

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
right lung	1
upper lobe of left lung	1
upper lobe of lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FCN3	172	tissue_specific	marker	right lung, upper lobe of left lung, upper lobe of lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FCN3	968

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FCN3	O75636	3

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
Ficolins bind to repetitive carbohydrate structures on the target cell surface	1	2284.0×	0.001	FCN3
Lectin pathway of complement activation	1	1268.9×	0.001	FCN3
Initial triggering of complement	1	601.0×	0.002	FCN3

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
negative regulation of RNA biosynthetic process	1	16852.0×	5e-04	FCN3
recognition of apoptotic cell	1	2407.4×	0.001	FCN3
complement activation, lectin pathway	1	1685.2×	0.001	FCN3
positive regulation of opsonization	1	1685.2×	0.001	FCN3
cell surface pattern recognition receptor signaling pathway	1	1404.3×	0.001	FCN3
host-mediated suppression of symbiont invasion	1	702.2×	0.002	FCN3
complement activation	1	624.1×	0.002	FCN3
defense response to virus	1	69.3×	0.016	FCN3
proteolysis	1	34.2×	0.029	FCN3

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
FCN3	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	FCN3

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)
FCN3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.