Alt. symbols: APT1LG1 | TNFSF6 | FasL | CD178

Approved name: Fas ligand
Alt. names: tumor necrosis factor (ligand) superfamily, member 6, Fas ligand (TNF superfamily, member 6)

Location: 1q24.3: 172659103 - 172666876 (+)
Gene type: protein_coding, 2 transcripts.

Scores: LoFtool: 0.071400 | pLI: 0.61167021 | LOEUF: 0.716

HGNC: 11936

NCBI: 356, RefSeq: NG_007269.1

Ensembl: ENSG00000117560.8

LRG_58 | Status: public

OMIM: 134638

Expression | ProteinAtlas

Fas ligand (FasL) is a homotrimeric type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family and that is expressed on cytotoxic T cells. Binding of FasL with its receptor (Fas or FasR) induces trimerization of FasR, which usually 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.

Both monoallelic and biallelic mutations in this gene have been associated with autoimmune lymphoproliferative syndrome (ALPS), type IB [MIM:601859]. The first reported mutation, a heterozygous 84-bp deletion within exon 4, was found in one patient initially diagnosed with SLE and lymphadenopathy (Wu J. et al 1996). And the first, and probably only, monoallelic dominant negative mutation (p.Arg156Gly) reported to date, was found in a North-American patient with ALPS (Bi, L. et al. 2007). However , there are more cases described with ALPS caused by biallelic loss of function mutations in FASLG, including two frameshift: p.Pro69Alafs*75 and p.Phe87fs*95, and two missense mutations: p.Ala247Glu and p.Gly277Ser (Del-Rey, M. et al. 2006; Magerus-Chatinet et al. 2013; Nabhani, S. et al. 2014; Sobh, A. et al. 2016). In addition, a polymorphism in the promoter region of FASLG (-844T-C) was associated with susceptibility to lung cancer [MIM:211980] (Zhang et al. 2005). The study showed that homozygous carriers (-844CC) had a more than 4-fold increased risk. Sun et al. (2005) found that the allele with -844T was expressed more highly on stimulated T cells than the allele with -844C. T cells with the -844C allele exhibited increased activation-induced cell death. This case-control study of Han Chinese women showed a statistically significant 3-fold increased risk of cervical cancer in -844CC homozygotes compared with -844TT homozygotes; but not in -844CT heterozygotes. Sun et al. (2005) proposed that polymorphisms in the FasR-FasL pathway confer susceptibility to cervical cancers, possibly caused by tumor cells escaping effector T cells due to enhanced activation-induced cell death. [Load More]