FCAR gene

The FCAR gene (FCAR stands for: Fc alpha Receptor) is a protein-coding gene that is localized on chromosome 19q13.42, in the Leucocyte Receptor Cluster (LRC). This localization is unusual, as the genes for other Fc receptors are usually located on chromosome 11. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. Individual gene variants (e.g. Ser/Gly at position 248) influence the ability to release cytokines such as IL-6 .

The gene belongs to the superfamily of immunoglobulin genes and encodes a receptor for the Fc region of IgA. The Fc alpha receptor is a transmembrane glycoprotein found on the surface of myeloid lineage cells such as neutrophils, monocytes, macrophages and eosinophils, where it mediates immunological responses to pathogens. The receptor protein binds to the Fc region of immunoglobulin alpha. Mediates several functions, including cytokine production. The encoded protein interacts with IgA-opsonized targets and triggers several immunological defense processes, including phagocytosis, antibody-dependent cell-mediated cytotoxicity and stimulation of inflammatory mediator release.

Diseases associated with FCAR gene include IgA glomerulonephritis and alcoholic liver cirrhosis (Huang W et al. 2011). Zhong Z et al. found that four SNPs (rs11264794, rs7865684, rs11264799 and rs6691569) are significantly associated with susceptibility to IgA glomerulonephritis.

Pemphigus foliaceus (PF) is a blistering autoimmune disease of the skin that occurs rarely worldwide but is endemic in certain regions of Brazil. PF is characterized by autoantibodies against desmoglein 1.

Genetic polymorphisms and variable expression levels in the leukocyte receptor complex (LRC) are associated with PF. Three SNPs are associated with different susceptibility to PF.

• The intergenic variant rs465169, which is located in a region that may regulate several immune-related genes, including VSTM1, LILRB1/2, LAIR1/2, LILRA3/4 and LENG8.
• The SNPs rs35336528 and rs1865097 in the LENG8 and FCAR genes.
• A further four haplotypes with SNPs within the KIR3, DL2/3, LAIR2 and LILRB1 genes associated with PF have been identified (Farias TDJ et al. 2019).

1. Farias TDJ et al. (2019) Screening the full leucocyte receptor complex genomic region revealed associations with pemphigus that might be explained by gene regulation. Immunology 156:86-93.

2. Huang W et al. (2011) Association of -27T>C and its haplotype at the putative promoter for IgA-specific receptor gene with IgA nephropathy among the Chinese Han population. Nephrol Dial Transplant 26:2537-2544.
3. Zhong Z et al. (2019) Association of FCRL3 Gene Polymorphisms with IgA Nephropathy in a Chinese Han Population. DNA Cell Biol 38:1155-1165.