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Fas

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Target id: 1875

Nomenclature: Fas

Systematic Nomenclature: TNFRSF6

Family: Tumour necrosis factor (TNF) receptor family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 335 10q23.31 FAS Fas cell surface death receptor
Mouse 1 327 19 29.48 cM Fas Fas cell surface death receptor
Rat 1 324 1q52 Fas Fas cell surface death receptor
Previous and Unofficial Names Click here for help
APO-1 | CD95 | apoptosis-mediating surface antigen FAS | Fas receptor | FASLG receptor | Fas cell surface death receptor | FAS1 | TNFRSF6A | Fas (TNF receptor superfamily member 6)
Database Links Click here for help
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
Fas ligand {Sp: Human}
Adaptor proteins (Human)
FADD
Immunopharmacology Comments
Fas receptor (CD95) is a cell surface protein that belongs to the tumor necrosis factor receptor family, that along with its ligand CD95L (or FasL), generates a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. This system is also important in the immune elimination of virus-infected cells, cancer cells and autoreactive T cells. Mouse strains with mutations in Fas or FasL develop lymphoproliferative conditions, indicating the importance of these proteins to immune cell homeostasis [3]. The phenotype of Fas-mutant mice presents in a systemic lupus erythematosus-like autoimmune disease [4]. Fas or FasL knockout mice show a more severe autoimmune phenotype than the mutant mice mentioned. Humans with type 1a and 1b autoimmune lymphoproliferative syndrome (ALPS) carry mutations in Fas and CD95L respectively. An epitope within the second of Fas' three external cysteine-rich domains has been identified as being crucial for Fas/FasL activation of apoptotic signalling in tumour cells and T cells [2]. This is an important discovery as Fas-mediated bystander killing is a vital component of the success of CAR-T cancer immunotherapies, as it may pave the way forward for improved efficacy of the CAR-T approach in solid tumours.
Immuno Process Associations
Immuno Process:  B cell (activation)
Immuno Process:  Cellular signalling
Immuno Process:  Cytokine production & signalling
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  T cell (activation)
Immuno Disease Associations
Disease Name:  Autoimmune lymphoproliferative syndrome; ALPS
Disease Synonyms:  no synonynms
Comment:  Type IA ALPS is caused by mutations in Fas receptor (CD95).
Disease X-refs:  Disease Ontology: DOID:6688
OMIM: 601859
Orphanet: ORPHA3261
References:  1
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0002722 abnormal immune system organ morphology PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0008750 abnormal interferon level PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0000717 abnormal lymphocyte cell number PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0005325 abnormal renal glomerulus morphology PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0002703 abnormal renal tubule morphology PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0008752 abnormal tumor necrosis factor level PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0002871 albuminuria PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0000702 enlarged lymph nodes PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0000691 enlarged spleen PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0002743 glomerulonephritis PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0001859 kidney inflammation PMID: 16267157 
Ccr2tm1Blck|Faslpr Ccr2tm1Blck/Ccr2tm1Blck,Faslpr/Faslpr
MRL.Cg-Ccr2 Fas
MGI:106185  MGI:95484  MP:0002083 premature death PMID: 16267157 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Autoimmune lymphoproliferative syndrome; ALPS
Description: ALPS covers a set of heterogenic heritable conditions characterised by a failure of apoptosis, that results in the accumulation of autoreactive lymphocytes. It manifests in early childhood as nonmalignant lymphadenopathy with hepatosplenomegaly and autoimmune cytopenias. Genes carrying ALPS-causing mutations include Fas receptor (type IA), fas ligand (type IB), caspase 10 (type IIA), caspase 8 (type IIB), PRKCD (ALPS3), NRAS (ALPS4) and CTLA4 (ALPS5).
Disease Ontology: DOID:6688
OMIM: 601859
Orphanet: ORPHA3261

References

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1. Bidère N, Su HC, Lenardo MJ. (2006) Genetic disorders of programmed cell death in the immune system. Annu Rev Immunol, 24: 321-52. [PMID:16551252]

2. Mondal T, Gaur H, Wamba BEN, Michalak AG, Stout C, Watson MR, Aleixo SL, Singh A, Condello S, Faller R et al.. (2023) Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer. Cell Death Differ, 30 (11): 2408-2431. [PMID:37838774]

3. Takahashi T, Tanaka M, Brannan CI, Jenkins NA, Copeland NG, Suda T, Nagata S. (1994) Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell, 76 (6): 969-76. [PMID:7511063]

4. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature, 356 (6367): 314-7. [PMID:1372394]

Contributors

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