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

ENSG00000026103 ∙ NCBI:355 ∙ OMIM:134637 ∙ HGNC:11920 ∙ Uniprot:P25445 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the FAS gene.

• Autoimmune lymphoproliferative syndrome type 1 (47 variants)
• not provided (8 variants)
• Autoimmune lymphoproliferative syndrome, type 1a (5 variants)
• FAS-related disorder (1 variants)
• Inborn genetic diseases (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	42	4	47
missense	10	13	139	10	1	173
nonsense	8	1		1		10
start loss						0
frameshift	21	7	1			29
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	10	4				14
splice region	2	2	13	4	2	23
non coding	1		20	37	36	94
Total	50	26	164	90	41

Highest pathogenic variant AF is 0.00000657

Variants in FAS

This is a list of pathogenic ClinVar variants found in the FAS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-88989499-G-A		LUNG CANCER, SUSCEPTIBILITY TO • not specified	Benign (Jan 24, 2024)
10-88990206-A-G		Autoimmune lymphoproliferative syndrome type 1	Benign (Dec 06, 2020)
10-88990523-TCC-T		Familial thoracic aortic aneurysm and aortic dissection • Autoimmune lymphoproliferative syndrome type 1 • Moyamoya disease • Multisystemic smooth muscle dysfunction syndrome	Likely benign (Jun 14, 2016)
10-88990530-C-T		Moyamoya disease • Autoimmune lymphoproliferative syndrome type 1 • Multisystemic smooth muscle dysfunction syndrome • Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Jun 14, 2016)
10-88990540-G-A		Multisystemic smooth muscle dysfunction syndrome • Moyamoya disease • Autoimmune lymphoproliferative syndrome type 1 • Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 14, 2016)
10-88990582-G-A		Multisystemic smooth muscle dysfunction syndrome • Autoimmune lymphoproliferative syndrome type 1 • Moyamoya disease • Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Jun 14, 2016)
10-88990589-C-T		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Jan 12, 2018)
10-88990703-G-A		Multisystemic smooth muscle dysfunction syndrome • Moyamoya disease • Familial thoracic aortic aneurysm and aortic dissection • Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Jun 14, 2016)
10-88990782-G-A		Familial thoracic aortic aneurysm and aortic dissection • Multisystemic smooth muscle dysfunction syndrome • Autoimmune lymphoproliferative syndrome type 1 • Moyamoya disease	Benign/Likely benign (Jun 14, 2016)
10-88990843-A-G		Multisystemic smooth muscle dysfunction syndrome • Autoimmune lymphoproliferative syndrome type 1 • Moyamoya disease • not specified • Familial thoracic aortic aneurysm and aortic dissection	Benign/Likely benign (Jun 14, 2016)
10-88990867-C-A		Autoimmune lymphoproliferative syndrome type 1 • Moyamoya disease • Familial thoracic aortic aneurysm and aortic dissection • Multisystemic smooth muscle dysfunction syndrome	Uncertain significance (Jun 14, 2016)
10-88990880-C-T		Autoimmune lymphoproliferative syndrome type 1	Likely benign (Jul 31, 2023)
10-88990888-C-G		FAS-related disorder	Uncertain significance (Mar 08, 2024)
10-88990891-G-C		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Sep 01, 2022)
10-88990896-T-C		Autoimmune lymphoproliferative syndrome type 1	Likely pathogenic (May 20, 2023)
10-88990903-T-C		Autoimmune lymphoproliferative syndrome type 1	Likely benign (Aug 01, 2023)
10-88990908-T-C		Autoimmune lymphoproliferative syndrome type 1 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 15, 2023)
10-88990912-C-T		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Jan 12, 2018)
10-88990918-C-T		Autoimmune lymphoproliferative syndrome type 1	Benign (Jan 22, 2024)
10-88990917-T-TCCTGC		Autoimmune lymphoproliferative syndrome type 1	Likely benign (Feb 14, 2023)
10-88990925-G-A		Autoimmune lymphoproliferative syndrome type 1	Benign (Jan 29, 2024)
10-88990925-G-T		Autoimmune lymphoproliferative syndrome type 1	Likely benign (Oct 13, 2023)
10-88990926-G-A		Autoimmune lymphoproliferative syndrome type 1	Likely benign (Mar 12, 2022)
10-88991152-C-T		not specified	Benign (Jan 24, 2024)
10-88991225-T-G		not specified	Benign (Jan 24, 2024)

GnomAD

Source: gnomAD

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
0.812	0.188	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: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.0909
• hipred: Y
• hipred_score: 0.671
• ghis: 0.432

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

Mouse Genome Informatics

• Gene name: Fas
• Phenotype: neoplasm; pigmentation phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; craniofacial phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

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