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FLASH GENE
Symbol FAS contributors: mct/ - updated : 05-03-2014
HGNC name Fas (TNF receptor superfamily, member 6)
HGNC id 11920
Corresponding disease
CSS1 Canale-Smith syndrome 1
TAL4 childhood acute lymphoblastic leukemia (T cell)
Location 10q23.31      Physical location : 90.750.287 - 90.775.541
Synonym name
  • cell differentiation antigen CD95
  • Fas antigen mediating apoptosis
  • FASLG receptor
  • APO-1 antigen
  • tumor necrosis factor receptor superfamily, member 6
  • CD95 antigen
  • Fas AMA
  • Synonym symbol(s) APO1, CD95, APT1, FASTM, TNR6, TNFRSF6, FAS1, LFG, ALPS1A, FAIM2, NMP35
    DNA
    TYPE functioning gene
    STRUCTURE 25.25 kb     9 Exon(s)
    regulatory sequence Promoter
    Binding site   transcription factor
    motif repetitive sequence   other
    text structure
  • SNP in the promoter playing a role in Alzheimer
  • G to A substitution at -1377 bp and an A to G substitution at -670 bp, which occur within SP1 and signal transducers and activators of transcription 1(variation in the promoter may affect gene expression and modulate apoptotic signaling)
  • one TP53 responsive-element within the first intron of the gene and 3 REs within the promoter
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 2755 37.7 335 - 2002 12359741
    8 splicing 2692 33.7 314 - 2002 12359741
  • lacking an in frame coding segment
  • precursor
  • 8 splicing 2730 23.1 220 - 2002 12359741
  • lacking a codin segment leading to a translation fameshift
  • precursor
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
     pharynx    
    Endocrineadrenal gland    
    Lymphoid/Immunethymus   highly
    Reproductivefemale systemuterus   
    Respiratorylung    
    Urinarybladder    
     kidney    
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period fetal
    Text muscle
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three extracytoplasmic cysteine-rich pseudo-repeats CRD1, CRD2, CRD3 typical for the TNFR superfamily
  • a preligand assembly domain (PLAD) in CRD1 mediating ligand-independent receptor assembly and signaling
  • a small cytoplasmic domain
  • a DEATH domain, associating under activation with the DEATH domain of FADD and CASP8
  • conjugated GlycoP
    mono polymer homomer , trimer
    HOMOLOGY
    Homologene
    FAMILY
  • tumor necrosis factor receptor superfamily
  • CATEGORY antigen , receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text isoforms lacking the transmembrane domain are secreted
    basic FUNCTION
  • mediating apoptosis of inactivated T cells for instance in negative regulation of erythropoiesis through sequential activation of ICE-like (CASP4, CASP5 and CPP32-like (CASP3)) caspases
  • blocking after stimulation T lymphocyte calcium channels through the activation of acidic sphingomyelinase (SMPD1) and ceramide release
  • involved in extra-thymic self-tolerance and tumor immune escape
  • playing a central role in the physiological regulation of programmed cell death, and involved in the pathogenesis of various malignancies and diseases of the immune system
  • activating NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells
  • isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform
  • its stimulation results in the formation of a novel death effector domain protein-containing complex
  • death receptor whose stimulation by either the physiologic ligand FASL or the agonistic antibodies leads to the formation of a multi-molecular complex termed DISC (death-inducing signaling complex)
  • death receptor that regulates tissue homeostasis mainly in the immune system through the induction of apoptosis
  • could actually promote the growth of tumours through its non-apoptotic activities
  • having a role in the tumorigenesis of ovarian cancer
  • induces a potent apoptotic signal
  • promotes apoptosis through well-defined signalling pathway
  • FAS/FASLG system plays a central role in maintaining peripheral immune tolerance
  • the site-specific FAS mRNA editing mutation may play a critical role in human immune responses and in the pathogenesis of human chronic inflammatory diseases
  • plays a pivotal role in immune surveillance and immune tolerance
  • induces invasion by stimulating the expression of extracellular matrix (ECM)-degrading proteases, and by stimulating the formation of actin-driven cell protrusions through Rac and the cofilin pathway
  • FAS-stimulation triggers localized Ca2+ influx through the redistribution of STIM1/ORAI1 into the FAS-Cap, and this influx inhibits the initial steps of the FAS signaling pathway
  • FAS-mediated Ca2+ response controls the initial steps in the receptor signaling pathway to promote the transmission of nonapoptotic signals
  • FAS and NFKB play a role in the initiation and development of breast cancer, while VEGFC appears to promote lymph node metastasis
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • trimerization may be dependent of TNFSF6 or independent
  • FAS/FASLG induces erythroblast apoptosis
  • FAS/FADD/caspase-8 complex is known as the death-inducing signaling complex (DISC)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding DAXX, RIPK1, FAIM2
  • interacting with HIPK3, BRE
  • interacting with CASP8AP2
  • interacting with CFL1 (cofilin activation is required for FAS-stimulated formation of membrane protrusions and increased tumour cell invasion)
  • biological role of Ca2+ and the ORAI1 channel that drives a transient negative feedback loop, introducing a lag phase in the early steps of the FAS signal (
  • hyperoxia-induced MAP1LC3B activation regulates the FAS apoptotic pathway and thus confers cytoprotection in lung epithelial cells (interaction of MAP1LC3B and FAS pathways requires CAV1)
  • LAT is proteolytically cleaved following FAS engagement in a tyrosine phosphorylation-dependent fashion
  • cell & other
    REGULATION
    activated by its natural ligand FASL (leads to the formation of the death-inducing signaling complex)
    induced by TP53-responsive elements, and TP63, TP73
    ASSOCIATED DISORDERS
    corresponding disease(s) CSS1 , TAL4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fusion with ESR1 in several cancer lines (prostate, breast cervical, bladder)
    tumoral somatic mutation      
    mutated in the death domain in the non small cell lung cancer, in non lymphoid malignancie, T cell lymphoma and Hodgkin's disease, thyroid lymphoma, nasal NK/T cell lymphoma
    tumoral       loss of function
  • retention of intron 5 and encodes a dysfunctional protein
  • impairment of Fas-induced apoptosis resulting from aberrant splicing potentially contributes to the development and progression of cutaneous T-cell lymphoma
  • tumoral somatic mutation      
    in nodal diffuse large B-cell lymphoma
    tumoral     --over  
    in epithelial ovarian cancer
    Susceptibility
  • implicated early-onset Alzheimer with inconsistant results
  • to autoimmune diabetes
  • systemic lupus erythematous with loss of regulation of B lymphocytes
  • to acute myeloid leukemia (AML)
  • to myocardial infarction (MI)
  • Variant & Polymorphism SNP , other
  • promoter playing a role in Alzheimer disease
  • increased risk of AML associated with heterozygotes (GA) and homozygote variants (AA) at position -1377 bp
  • SNP (-670G/A), may be a risk factor of MI occurrence
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    locking FAS in apoptosis-mode may be a more promising anti-cancer strategy than simply inhibiting or stimulating FAS
    ANIMAL & CELL MODELS