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FASLG Fas ligand [ Homo sapiens (human) ]

Gene ID: 356, updated on 1-Jun-2020

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

Genomic context

See FASLG in Genome Data Viewer
Location:
1q24.3
Exon count:
4
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (172659008..172666876)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (172628185..172636013)

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 solute carrier family 25 member 38 pseudogene 1 Neighboring gene uncharacterized LOC107985225

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
Lung cancer
MedGen: C0684249 OMIM: 211980 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.
NHGRI GWA Catalog
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog
Multiple common variants for celiac disease influencing immune gene expression.
NHGRI GWA Catalog

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

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_001302746.1NP_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
    Consensus CDS
    CCDS76243.1
    UniProtKB/Swiss-Prot
    P48023
    Related
    ENSP00000344739.3, ENST00000340030.4

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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
    172659008..172666876
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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