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target has curated data in GtoImmuPdb
Target id: 1875
Nomenclature: Fas
Systematic Nomenclature: TNFRSF6
Gene and Protein Information  |
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| 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 |
| 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 |
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| Alphafold | P25445 (Hs), P25446 (Mm), Q63199 (Rn) |
| ChEMBL Target | CHEMBL4523207 (Hs), CHEMBL2417350 (Rn) |
| Ensembl Gene | ENSG00000026103 (Hs), ENSMUSG00000024778 (Mm), ENSRNOG00000019142 (Rn) |
| Entrez Gene | 355 (Hs), 14102 (Mm), 246097 (Rn) |
| Human Protein Atlas | ENSG00000026103 (Hs) |
| KEGG Gene | hsa:355 (Hs), mmu:14102 (Mm), rno:246097 (Rn) |
| OMIM | 134637 (Hs) |
| Pharos | P25445 (Hs) |
| UniProtKB | P25445 (Hs), P25446 (Mm), Q63199 (Rn) |
| Wikipedia | FAS (Hs) |
| Natural/Endogenous Ligands |
| 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 | ||
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| Immuno Disease Associations | ||||||||||
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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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]
