Ficolin-1 is an extracellular lectin that functions as a pattern recognition receptor, initiating the lectin pathway of complement activation by recognizing and binding to carbohydrates on pathogen surfaces. The gene shows very low constraint against loss-of-function variants (pLI near zero, LOEUF 1.82), and no clear Mendelian diseases have been definitively associated with FCN1 mutations. While ficolin-1 may play a role in innate immunity and complement activation, the clinical significance of FCN1 variants in pediatric neurological conditions remains unclear.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.81
Clinical SummaryFCN1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.81LOEUF
pLI 0.000
Z-score -1.20
OE 1.32 (0.941.81)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.29Z-score
OE missense 1.06 (0.941.19)
214 obs / 202.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.32 (0.941.81)
00.351.4
Missense OE1.06 (0.941.19)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 22 / 16.7Missense obs/exp: 214 / 202.3Syn Z: -0.83
DN
0.74top 25%
GOF
0.6638th %ile
LOF
0.2776th %ile

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.

DNprediction above median
GOFprediction above median

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FCN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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