FAS
Fas cell surface death receptor, the group of CD molecules|Tumor necrosis factor receptor superfamily|Death inducing signaling complex
Basic information
Region (hg38): 10:88953813-89029605
Previous symbols: [ "FAS1", "APT1", "TNFRSF6" ]
Links
Phenotypes
GenCC
Source:
- autoimmune lymphoproliferative syndrome type 1 (Definitive), mode of inheritance: AD
- autoimmune lymphoproliferative syndrome (Supportive), mode of inheritance: AD
- autoimmune lymphoproliferative syndrome type 1 (Strong), mode of inheritance: AD
- autoimmune lymphoproliferative syndrome type 1 (Moderate), mode of inheritance: AR
- autoimmune lymphoproliferative syndrome (Definitive), mode of inheritance: AD
- autoimmune lymphoproliferative syndrome (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Autoimmune lymphoproliferative syndrome, type IA | AD/AR | Allergy/Immunology/Infectious; Oncologic | Lymphoproliferation can be suppressed with medications such as corticosteroids, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil; BMT/HSCT the only curative treatment for ALPS, has to date mostly been reported in patients with severe clinical findings; Surveillance for manifestations of lymphoproliferation and autoimmunity, and specialized imaging studies to detect malignant transformation may be beneficial | Allergy/Immunology/Infectious; Hematologic; Oncologic; Renal | 4165068; 1386609; 7540117; 8929361; 10709732; 15459302; 20301287 |
ClinVar
This is a list of variants' phenotypes submitted to
- Autoimmune_lymphoproliferative_syndrome_type_1 (391 variants)
- not_provided (68 variants)
- Inborn_genetic_diseases (22 variants)
- not_specified (20 variants)
- AUTOIMMUNE_LYMPHOPROLIFERATIVE_SYNDROME,_TYPE_IA (17 variants)
- FAS-related_disorder (9 variants)
- SQUAMOUS_CELL_CARCINOMA,_BURN_SCAR-RELATED,_SOMATIC (3 variants)
- Splenomegaly (1 variants)
- Autoimmune_lymphoproliferative_syndrome (1 variants)
- Inherited_Immunodeficiency_Diseases (1 variants)
- See_cases (1 variants)
- Hepatoblastoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FAS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000043.6. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 57 | 2 | 61 | ||
| missense | 19 | 23 | 186 | 12 | 240 | |
| nonsense | 12 | 3 | 2 | 17 | ||
| start loss | 0 | |||||
| frameshift | 28 | 12 | 2 | 42 | ||
| splice donor/acceptor (+/-2bp) | 11 | 7 | 5 | 23 | ||
| Total | 70 | 45 | 197 | 69 | 2 |
Highest pathogenic variant AF is 0.000016731838
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FAS | protein_coding | protein_coding | ENST00000355740 | 9 | 25129 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 125734 | 0 | 2 | 125736 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.23 | 121 | 166 | 0.731 | 0.00000803 | 2214 |
| Missense in Polyphen | 22 | 53.688 | 0.40977 | 746 | ||
| Synonymous | 0.399 | 55 | 58.9 | 0.934 | 0.00000300 | 591 |
| Loss of Function | 3.01 | 2 | 14.3 | 0.140 | 6.14e-7 | 189 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death- inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS- mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro). {ECO:0000269|PubMed:19118384, ECO:0000269|PubMed:7533181}.;
- Disease
- DISEASE: Autoimmune lymphoproliferative syndrome 1A (ALPS1A) [MIM:601859]: A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia. {ECO:0000269|PubMed:10090885, ECO:0000269|PubMed:10340403, ECO:0000269|PubMed:10515860, ECO:0000269|PubMed:11418480, ECO:0000269|PubMed:17336828, ECO:0000269|PubMed:20935634, ECO:0000269|PubMed:7540117, ECO:0000269|PubMed:8929361, ECO:0000269|PubMed:9028321, ECO:0000269|PubMed:9028957, ECO:0000269|PubMed:9322534, ECO:0000269|PubMed:9821419, ECO:0000269|PubMed:9927496}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Type I diabetes mellitus - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Allograft rejection - Homo sapiens (human);Graft-versus-host disease - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Autoimmune thyroid disease - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Apoptosis - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);miRNA Regulation of DNA Damage Response;Apoptosis Modulation and Signaling;Alzheimers Disease;Allograft Rejection;Adipogenesis;Nanomaterial induced apoptosis;Integrated Lung Cancer Pathway;Apoptosis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Photodynamic therapy-induced AP-1 survival signaling.;Apoptotic Signaling Pathway;TP53 Regulates Transcription of Cell Death Genes;MAPK Signaling Pathway;Apoptosis Modulation by HSP70;VEGFA-VEGFR2 Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;DNA Damage Response;Signal Transduction;Gene expression (Transcription);il-2 receptor beta chain in t cell activation;hiv-1 nef: negative effector of fas and tnf;stress induction of hsp regulation;keratinocyte differentiation;Generic Transcription Pathway;Fas;TP53 Regulates Transcription of Cell Death Genes;Regulation of necroptotic cell death;Dimerization of procaspase-8;Regulation by c-FLIP;Ligand-dependent caspase activation;RNA Polymerase II Transcription;Caspase activation via extrinsic apoptotic signalling pathway;Apoptosis;CASP8 activity is inhibited;Regulated Necrosis;Programmed Cell Death;p73 transcription factor network;RIPK1-mediated regulated necrosis;fas signaling pathway (cd95);FasL/ CD95L signaling;Validated transcriptional targets of TAp63 isoforms;Death Receptor Signalling;Transcriptional Regulation by TP53;Direct p53 effectors;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;FAS (CD95) signaling pathway;TP53 Regulates Transcription of Death Receptors and Ligands
(Consensus)
Recessive Scores
- pRec
- 0.872
Intolerance Scores
- loftool
- 0.0628
- rvis_EVS
- 0.46
- rvis_percentile_EVS
- 78.46
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.597
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Zebrafish Information Network
- Gene name
- fas
- Affected structure
- post-vent region
- Phenotype tag
- abnormal
- Phenotype quality
- increased curvature
Gene ontology
- Biological process
- positive regulation of protein phosphorylation;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;immune response;signal transduction;regulation of stress-activated MAPK cascade;cellular response to amino acid starvation;Fas signaling pathway;regulation of apoptotic process;positive regulation of apoptotic process;negative regulation of apoptotic process;protein-containing complex assembly;cellular response to mechanical stimulus;cellular response to hyperoxia;apoptotic signaling pathway;extrinsic apoptotic signaling pathway;necroptotic signaling pathway;regulation of extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors;positive regulation of apoptotic signaling pathway;positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
- Cellular component
- cytosol;plasma membrane;cell surface;integral component of membrane;nuclear body;death-inducing signaling complex;CD95 death-inducing signaling complex;membrane raft;extracellular exosome
- Molecular function
- transmembrane signaling receptor activity;protein binding;calmodulin binding;kinase binding;signaling receptor activity;identical protein binding