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    FASLG Fas ligand [ Homo sapiens (human) ]

    Gene ID: 356, updated on 19-Jul-2021

    Summary

    Official Symbol
    FASLGprovided by HGNC
    Official Full Name
    Fas ligandprovided by HGNC
    Primary source
    HGNC:HGNC:11936
    See related
    Ensembl:ENSG00000117560 MIM:134638
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    APTL; FASL; CD178; CD95L; ALPS1B; CD95-L; TNFSF6; TNLG1A; APT1LG1
    Summary
    This gene is a member of the tumor necrosis factor superfamily. The primary function of the encoded transmembrane protein is the induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death. It has also been implicated in the progression of several cancers. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2014]
    Expression
    Broad expression in lymph node (RPKM 2.5), spleen (RPKM 1.7) and 21 other tissues See more
    Orthologs
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    Genomic context

    See FASLG in Genome Data Viewer
    Location:
    1q24.3
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (172659103..172666876)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (172628243..172636016)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene SUN domain containing ossification factor Neighboring gene RNA, U6 small nuclear 693, pseudogene Neighboring gene Sharpr-MPRA regulatory region 4605 Neighboring gene solute carrier family 25 member 38 pseudogene 1

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Autoimmune lymphoproliferative syndrome Compare labs
    Autoimmune lymphoproliferative syndrome, type 1b
    MedGen: C1866120 GeneReviews: Not available
    Compare labs
    Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.
    GeneReviews: Not available
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    GeneReviews: Not available
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    GeneReviews: Not available
    Lung cancer
    MedGen: C0242379 OMIM: 211980 GeneReviews: Not available
    Compare labs
    Lung carcinoma
    MedGen: C0684249 GeneReviews: Not available
    Compare labs
    Multiple common variants for celiac disease influencing immune gene expression.
    GeneReviews: Not available

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 binds and signals through CD4, which leads to T cell activation with upregulation of the CXCR5, PD-1, Fas, and FasL expression PubMed
    env At high concentrations, HIV-1 gp120 enhances expression of Fas and FasL and promotes apoptosis in human mesangial cells (HMC) PubMed
    env Apoptosis induced by HIV-1 gp120/CD4 cross-linking in Th1 clones is inhibited by anti-CD95 or anti-CD95L neutralizing monoclonal antibodies, as well as by a specific interleukin-1 beta converting enzyme (ICE) inhibitor PubMed
    env Preincubation of T cells with HIV-1 gp120 accelerates the apoptosis observed during CD2-pathway stimulation of the T cells; this process is mediated by Fas/Fas ligand interaction and related to an increased induction of Fas ligand mRNA by gp120 PubMed
    env Binding of HIV-1 gp120 to CD4 downregulates Bcl-2 protein in CD4+ T lymphocytes and facilitates Fas/Fas-ligand triggered apoptosis; addition of IL-2 rescues CD4+ T cells from CD4/gp120-induced Bcl-2 down modulation and apoptosis induction PubMed
    env Depletion of CD4 and CD8 T cells by HIV-1 gp120 is mediated by Fas ligand PubMed
    Envelope surface glycoprotein gp160, precursor env HIV-1 Env co-localizes with FasL in HIV-1 infected CD4+ T cells PubMed
    Nef nef HIV-1 Nef upregulates Fas ligand expression in gene-transfected hepatic cells from rat liver allografts PubMed
    nef Upregulation of Fas ligand by HIV-1 Nef is mediated through a direct interaction of Nef with the T cell Receptor zeta chain and binding of Nef to the Nef-associated kinase (NAK/p62) PubMed
    nef HIV-1 Nef sensitizes CD4+ T lymphoid cells to apoptosis by upregulating the expression of both Fas and Fas ligand, an effect that requires the PxxP motif (amino acids 72-75) in the core region of Nef PubMed
    nef The PxxP domain of HIV-1 Nef is required for upregulation of Fas ligand transcription and p38 MAPK activation by Nef PubMed
    nef Experiments using a dominant-negative isoform of p38 MAPK, p38 siRNA, and inhibitors of p38 activation indicate that p38 is required for HIV-1 Nef-induced Fas ligand upregulation PubMed
    nef Increased expression of Fas ligand was observed in CD4(+) and CD8(+) T cells from Transgenic (Tg) mice expressing HIV-1 Nef compared to that of non-Tg mice PubMed
    Tat tat HIV-1 Tat101 induces more protection against FasL-mediated apoptosis than HIV-1 Tat72 or negative control in FasL-treated CD4+ T cells PubMed
    tat FasL-induced cleavage of BID/p22 and BCL2 is inhibited in HIV-1 Tat101-expressing Jurkat cells PubMed
    tat FasL-induced release of cytochrome c and activation of caspase-9 are inhibited in HIV-1 Tat101-expressing Jurkat cells due to high stability of the mitochondrial inner membrane electrochemical potential PubMed
    tat FasL-induced activation of caspase-3 and -8 proteins is inhibited in HIV-1 Tat101-expressing Jurkat cells PubMed
    tat HIV-1 Tat has a synergistic effect on Cryptosporidium parvum-induced cholangiocyte apoptosis via a paracrine-mediated, FasL-dependent mechanism PubMed
    tat HIV-1 Tat upregulates FasL expression by enhancing Egr-dependent and NF-kappaB mediated transactivation of the FasL promoter PubMed
    tat HIV-1 Tat sensitizes T cells to CD95 mediated apoptosis through the upregulation of CD95 ligand and caspase 8 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytokine activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables death receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables signaling receptor binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables tumor necrosis factor receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in T cell apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within activation of cysteine-type endopeptidase activity involved in apoptotic process IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cell-cell signaling TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cellular chloride ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to interferon-gamma IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in endosomal lumen acidification IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in extrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in extrinsic apoptotic signaling pathway via death domain receptors IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    acts_upstream_of_or_within extrinsic apoptotic signaling pathway via death domain receptors IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in extrinsic apoptotic signaling pathway via death domain receptors IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in inflammatory cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in necroptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in necroptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of angiogenesis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of I-kappaB kinase/NF-kappaB signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in positive regulation of I-kappaB kinase/NF-kappaB signaling IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    acts_upstream_of_or_within positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of endothelial cell apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of epidermal growth factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of phosphatidylserine exposure on apoptotic cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within release of sequestered calcium ion into cytosol by endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to growth factor IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in retinal cell programmed cell death IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in caveola IEA
    Inferred from Electronic Annotation
    more info
     
    located_in cytoplasmic vesicle lumen IEA
    Inferred from Electronic Annotation
    more info
     
    located_in external side of plasma membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in integral component of plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in lysosomal lumen IEA
    Inferred from Electronic Annotation
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
     
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    tumor necrosis factor ligand superfamily member 6
    Names
    CD95 ligand
    Fas ligand (TNF superfamily, member 6)
    apoptosis (APO-1) antigen ligand 1
    apoptosis antigen ligand
    fas antigen ligand
    mutant tumor necrosis factor family member 6
    tumor necrosis factor ligand 1A

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007269.1 RefSeqGene

      Range
      4964..12829
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_58

    mRNA and Protein(s)

    1. NM_000639.3NP_000630.1  tumor necrosis factor ligand superfamily member 6 isoform 1

      See identical proteins and their annotated locations for NP_000630.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      X89102, Z96050
      Consensus CDS
      CCDS1304.1
      UniProtKB/Swiss-Prot
      P48023
      UniProtKB/TrEMBL
      Q53ZZ1
      Related
      ENSP00000356694.2, ENST00000367721.3
      Conserved Domains (1) summary
      cd00184
      Location:146279
      TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...
    2. NM_001302746.2NP_001289675.1  tumor necrosis factor ligand superfamily member 6 isoform 2

      See identical proteins and their annotated locations for NP_001289675.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in the 5' coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AF288573, DA916336, X89102, Z96050
      Consensus CDS
      CCDS76243.1
      UniProtKB/Swiss-Prot
      P48023
      Related
      ENSP00000344739.3, ENST00000340030.4

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

      Range
      172659103..172666876
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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