FASLG Fas ligand [Homo sapiens (human)] - Gene

Summary

Official Symbol: FASLGprovided by HGNC
Official Full Name: Fas ligandprovided by HGNC
Primary source: HGNC:HGNC:11936
See related: Ensembl:ENSG00000117560 MIM:134638; AllianceGenome:HGNC:11936
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: mouse all
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Genomic context

Location:: 1q24.3

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (172659103..172666876)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (172016214..172023987)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (172628243..172636016)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Synthesis of N-Glycosylated Soluble Fas Ligand.
Title: Synthesis of N-Glycosylated Soluble Fas Ligand.
CD95L concatemers highlight different stoichiometries of CD95-mediated apoptotic and nonapoptotic pathways.
Title: CD95L concatemers highlight different stoichiometries of CD95-mediated apoptotic and nonapoptotic pathways.
The complex web of FasL: cell type-specific roles in affecting and controlling acute graft-vs-host disease.
Title: The complex web of FasL: cell type-specific roles in affecting and controlling acute graft-vs-host disease.
Plasma Levels of sFas-sFasL and FASL Gene Expression Are Associated with Tuberculosis.
Title: Plasma Levels of sFas-sFasL and FASL Gene Expression Are Associated with Tuberculosis.
Fas cell surface death receptor/Fas ligand genetic variants in gastric cancer patients: A case-control study.
Title: Fas cell surface death receptor/Fas ligand genetic variants in gastric cancer patients: A case-control study.
The role of FASL, BCL-2 and BAX polymorphisms in brazilian patients with prostate cancer and benign prostatic hyperplasia.
Title: The role of FASL, BCL-2 and BAX polymorphisms in brazilian patients with prostate cancer and benign prostatic hyperplasia.
miR-24-3p down-regulates the expression of the apoptotic factors FasL and BIM in human natural killer cells.
Title: miR-24-3p down-regulates the expression of the apoptotic factors FasL and BIM in human natural killer cells.
Cleaved CD95L perturbs in vitro macrophages responses to Toxoplasma gondii.
Title: Cleaved CD95L perturbs in vitro macrophages responses to Toxoplasma gondii.
Cord blood soluble Fas ligand linked to allergic rhinitis and lung function in seven-year-old children.
Title: Cord blood soluble Fas ligand linked to allergic rhinitis and lung function in seven-year-old children.
Differential cancer risk and survival in Indian oral cancer patients with genic region FAS and FASL polymorphisms.
Title: Differential cancer risk and survival in Indian oral cancer patients with genic region FAS and FASL polymorphisms.

Submit: New GeneRIF Correction See all GeneRIFs (553)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autoimmune lymphoproliferative syndrome type 1 MedGen: C1328840 OMIM: 601859 GeneReviews: Autoimmune Lymphoproliferative Syndrome	Compare labs
Autoimmune lymphoproliferative syndrome, type 1b MedGen: C1866120 GeneReviews: Not available	Compare labs
Lung cancer MedGen: C0242379 OMIM: 211980 GeneReviews: Not available	Compare labs
Lung carcinoma MedGen: C0684249 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S3717 (e-PCR)
- UniSTS:10533

PMC86001P1 (e-PCR)
- UniSTS:273502

PMC86001P2 (e-PCR)
- UniSTS:273503

PMC135646P4 (e-PCR)
- UniSTS:270768

D1S3209 (e-PCR)
- UniSTS:75969

G42266 (e-PCR)
- UniSTS:93939

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine activity	IDA Inferred from Direct Assay more info	PubMed
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 apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to type II interferon	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
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 intracellular chloride ion homeostasis	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
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 canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IEP Inferred from Expression Pattern 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 extrinsic apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor 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
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay 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

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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)

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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

NG_007269.1 RefSeqGene

Range

4964..12829

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_58

mRNA and Protein(s)

NM_000639.3 → NP_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, Q9BZP9

UniProtKB/TrEMBL

A0A0H3VB22, Q0VHD7, Q53ZZ1

Related

ENSP00000356694.2, ENST00000367721.3

Conserved Domains (1) summary

cd00184
Location:146 → 279

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 ...
NM_001302746.2 → NP_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