Alt. symbols: FAS1 | APT1 | TNFRSF6 | CD95 | APO-1

Approved name: Fas cell surface death receptor
Alt. names: tumor necrosis factor receptor superfamily, member 6, Fas (TNF receptor superfamily, member 6) | TNF receptor superfamily member 6

Location: 10q23.31: 88953813 - 89029605 (+)
Gene type: protein_coding, 61 transcripts.

Scores: LoFtool: 0.062800 | pLI: 0.72617334 | LOEUF: 0.441

HGNC: 11920

NCBI: 355, RefSeq: NG_009089.2

Ensembl: ENSG00000026103.25

LRG_134 | Status: public

OMIM: 134637

Expression | ProteinAtlas

This gene encodes for a cell surface protein receptor known as Fas (or FasR). Binding of Fas-ligand (FasL) to FasR induces its trimerization and initiates the caspase cascade, which ultimately leads to apoptosis, or cell death. FasL/FasR signalling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells, cytotoxic T lymphocyte induced cell death and natural killer cell-mediated apoptosis, or for the progression of cancer. It is suspected that FAS-mediated apoptosis has also a role in the induction of peripheral tolerance. Soluble Fas ligand is generated by cleaving membrane-bound FasL at a conserved cleavage site by the external matrix metalloproteinase MMP-7. This cytoplasmic form induces gene transcription inhibition.

Monoallelic mutations in FAS cause the most common and best-characterized form of autoimmune lymphoproliferative syndrome (ALPS, type IA) [MIM:601859]. In ALPS-FAS non-malignant lymphoproliferation typically manifests in the first years of life, which often decreases without treatment in the second decade of life. However, in many patients neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. Biallelic mutations in FAS cause severe lymphoproliferation perinatally and usually results in early death. Somatic mutations can cause a similar phenotype to that observed in individuals with heterozygous germline FAS mutations, although lower incidence of splenectomy and lower lymphocyte counts are observed. In addition FAS mutations have been associated with increased risk of developing cancer, including cancers of the lung, breast, and esophagus. More than 115 mutations in FAS have been associated with disease thus far. [Load More]