FCN2
Chr 9ficolin 2
Also known as: EBP-37, FCNL, P35, ficolin-2
FCN2 encodes ficolin-2, a calcium-dependent lectin that functions as a pattern recognition receptor, binding carbohydrates on pathogen surfaces and initiating the lectin pathway of complement activation to enhance immune responses. Mutations cause ficolin-2 deficiency, an autosomal recessive primary immunodeficiency that predisposes to recurrent infections, particularly respiratory tract infections. The gene is highly tolerant to loss-of-function variants (very low pLI), consistent with the recessive inheritance pattern observed in clinical practice.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
119 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 43 | 0 | 43 |
Likely Pathogenic | 1 | 0 | 1 | 0 | 2 |
VUS | 0 | 52 | 13 | 0 | 65 |
Likely Benign | 0 | 1 | 0 | 1 | 2 |
Benign | 0 | 5 | 1 | 1 | 7 |
| Total | 1 | 58 | 58 | 2 | 119 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FCN2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools