FCN1
protein-codingficolin 1, the group of Complement system activation components|Fibrinogen C domain containing
Gene summary
The ficolin family of proteins are characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. The collagen-like and the fibrinogen-like domains are also found separately in other proteins such as complement protein C1q, C-type lectins known as collectins, and tenascins. However, all these proteins recognize different targets, and are functionally distinct. Ficolin 1 encoded by FCN1 is predominantly expressed in the peripheral blood leukocytes, and has been postulated to function as a plasma protein with elastin-binding activity. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FCN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002003.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 20 | 20 | ||||
| missense | 58 | 4 | 62 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 63 | 24 | 0 | 87 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001994.2 | 9 | MANE Select | |
| Ensembl | ENSP00000360871.3 | 9 | MANE Select | |
| Ensembl | ENSP00000537980.1 | 7 | Standard | |
| Ensembl | ENSP00000537980.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Human Complement System
- Neutrophil degranulation
- Innate Immune System
- Immune System
- Initial triggering of complement
Biological Process
- complement activation, lectin pathway
- cell surface pattern recognition receptor signaling pathway
- proteolysis
- complement activation
- G protein-coupled receptor signaling pathway
Molecular Function
- G protein-coupled receptor binding
- serine-type endopeptidase activity
- protein binding
- signaling pattern recognition receptor activity
- carbohydrate binding
Cellular Component
- extracellular region
- collagen trimer
- extrinsic component of external side of plasma membrane
- secretory granule lumen
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371806
- Coding exons
- 9
- Length
- 8379
- Individuals with no LoFs
- 125424
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 324
- Defined
- 125748
- p
- 0.00129
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.292 | 214 | 202 | 1.06 | 0.0000126 | 2108 |
| Missense (PolyPhen) | 71 | 70.613 | 1.0055 | 791 | ||
| Synonymous | -0.829 | 94 | 84.3 | 1.11 | 0.00000574 | 641 |
| Loss of Function | -1.20 | 22 | 16.7 | 1.32 | 9.81e-7 | 171 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00093 | 0.00093 | rare |
| Ashkenazi Jewish | 0.0072 | 0.0072 | notable |
| East Asian | 0.0047 | 0.0047 | notable |
| Finnish | 0.00039 | 0.00037 | rare |
| European (Non-Finnish) | 0.00079 | 0.00078 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0.0031 | 0.0031 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Extracellular lectin functioning as a pattern- recognition receptor in innate immunity. Binds the sugar moieties of pathogen-associated molecular patterns (PAMPs) displayed on microbes and activates the lectin pathway of the complement system. May also activate monocytes through a G protein-coupled receptor, FFAR2, inducing the secretion of interleukin-8/IL-8 (PubMed:21037097). Binds preferentially to 9-O-acetylated 2-6- linked sialic acid derivatives and to various glycans containing sialic acid engaged in a 2-3 linkage. {ECO:0000269|PubMed:20032467, ECO:0000269|PubMed:21037097}.;
Intolerance Scores
- LoFtool
- 0.434
- RVIS EVS
- -0.26
- RVIS percentile EVS
- 34.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.260
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |