Alt. symbols: FCNH | HAKA1

Approved name: ficolin 3
Alt. names: ficolin (collagen/fibrinogen domain-containing) 3 (Hakata antigen), ficolin (collagen/fibrinogen domain containing) 3 | Hakata antigen

Location: 1p36.11: 27369110 - 27374824 (-)
Gene type: protein_coding, 6 transcripts.

Scores: LoFtool: 0.600000 | pLI: 0.01725134 | LOEUF: 0.896

HGNC: 3625

NCBI: 8547, RefSeq: NG_016279.1

Ensembl: ENSG00000142748.14

LRG_171 | Status: public

OMIM: 604973

Expression | ProteinAtlas

The FCN3 gene encodes ficolin-3, a multimeric lectin protein that plays an important role in innate immunity through the activation of the lectin complement pathway. Ficolins are a group of proteins that are made of of a cysteine-rich domain (where monomers bind to each other), a collagen-like domain and a fibrinogen-like domain. Ficolin-3 is a is a thermolabile beta-2-macroglycoprotein found in all human serum that has affinity with GalNAc, GlcNAc, D-fucose, as mono/oligosaccharide and lipopolysaccharides from S.typhimurium and S.minnesota. The protein can activate the complement system through the lectin pathway, in association with MASPs and sMAP, thereby aiding in host defense against pathogens. According to RNA expression data (HPA, GTEx and FANTOM5 datasets) FCN3 is mainly expressed in the lungs and, with a less extend, in the liver. However, protein expression analysis shows that, besides the lungs and liver, ficolin-3 is also found in various organs in the body, but primarily in the brain, the endocrine glands, and the gastrointestinal tract. Ficolin-3 was initially known as H-ficolin or the Hakata antigen, because it was initially found as an autoantigen in sera from patients with systemic lupus erythematosus who lived in the city of Hakata.

Ficolin 3 deficiency (FCN3D) [MIM: 613860]: An autosomal recessive disorder characterized by immunodeficiency, recurrent infections, brain abscesses and recurrent warts on the fingers. Affected individuals have normal levels of lymphocytes, normal T-cell responses, and normal antibodies, but a selective deficient antibody response to pneumococcal polysaccharide vaccine (PMID: 19535802). To date, the only variant that has ever been linked to disease susceptibility in FCN3 is the c.349delC / p.Leu 117Serfs*65, which is found in the literature as g.1637delC. According to gnomAD populations, this polymorphism has an allele frequency of ~1.6-1.8%, being present in heterozygosity in 3.14-3.6% of control individuals, and in homozygosity in 0.042-0.046% of individuals. Heterozygous carriers have reduced serum levels of ficolin-3 and are healthy, but homozygous individuals lack ficolin-3 in serum. This has been associated with immunodeficiency in 1 individual (Munthe-Fog et al., 2009), and with necrotising enterocolitis in 2 premature neonates (Schlapbach et al., 2011). Michalski and colleagues also reported 3 cases (one adult and two infants) with diverse clinical presentations carrying this homozygous variant (Michalski et al. 2012, Michalski et al. 2015). Michaski et al. (2012) also observed that both pre-term deliveries and low birthweight were significantly associated with low H-ficolin concentrations in serum but not with heterozygosity for the g.1637delC frameshift mutation. The role of ficolin-3 serum levels was also evaluated in patients with leprosy (Andrade et al., 2017), and the authors suggested that those polymorphisms in FCN3 that cooperate to increase ficolin-3 concentration in serum, might contribute to leprosy susceptibility. [Load More]