FCN2
protein-codingficolin 2, the group of Fibrinogen C domain containing|Complement system activation components
Gene summary
The product of this gene belongs to the ficolin family of proteins. This family is 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. This gene is predominantly expressed in the liver, and has been shown to have carbohydrate binding and opsonic activities. Alternatively spliced transcript variants encoding different isoforms have been identified. [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 ~6.7 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 FCN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004108.3. 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 | 11 | 1 | 12 | |||
| missense | 54 | 5 | 59 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 54 | 16 | 1 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004099.2 | 8 | MANE Select | |
| Ensembl | ENSP00000291744.6 | 8 | MANE Select | |
| RefSeq | NP_056652.1 | 7 | Standard | |
| Ensembl | ENSP00000291741.5 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Human Complement System
- Innate Immune System
- Immune System
- Initial triggering of complement
- Ficolins bind to repetitive carbohydrate structures on the target cell surface
Biological Process
- complement activation, lectin pathway
- proteolysis
- complement activation
- opsonization
- recognition of apoptotic cell
Molecular Function
- antigen binding
- serine-type endopeptidase activity
- protein binding
- proteoglycan binding
- metal ion binding
Cellular Component
- extracellular region
- collagen trimer
- extracellular exosome
- blood microparticle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000291744
- Coding exons
- 8
- Length
- 7271
- Individuals with no LoFs
- 125493
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 254
- Defined
- 125748
- p
- 0.00101
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.361 | 204 | 190 | 1.07 | 0.0000113 | 2009 |
| Missense (PolyPhen) | 64 | 57.809 | 1.1071 | 694 | ||
| Synonymous | -0.767 | 90 | 81.2 | 1.11 | 0.00000523 | 633 |
| Loss of Function | -0.0309 | 16 | 15.9 | 1.01 | 9.52e-7 | 150 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00070 | 0.00068 | rare |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0074 | 0.0074 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00056 | 0.00055 | rare |
| South Asian | 0.00086 | 0.00085 | rare |
| Other | 0.00099 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May function in innate immunity through activation of the lectin complement pathway. Calcium-dependent and GlcNAc- binding lectin. Enhances phagocytosis of S.typhimurium by neutrophils, suggesting an opsonic effect via the collagen region. {ECO:0000269|PubMed:10679061, ECO:0000269|PubMed:17215869}.;
Recessive Scores
- pRec
- 0.0963
Intolerance Scores
- LoFtool
- 0.573
- RVIS EVS
- 0.58
- RVIS percentile EVS
- 82.3
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.421
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | Medium | High |