FASLG

Fas ligand, the group of CD molecules|Tumor necrosis factor superfamily|Death inducing signaling complex

Basic information

Region (hg38): 1:172659102-172666876

Previous symbols: [ "APT1LG1", "TNFSF6" ]

Links

ENSG00000117560 ∙ NCBI:356 ∙ OMIM:134638 ∙ HGNC:11936 ∙ Uniprot:P48023 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autoimmune lymphoproliferative syndrome (Supportive), mode of inheritance: AD
• autoimmune lymphoproliferative syndrome type 1 (Limited), mode of inheritance: AD
• autoimmune lymphoproliferative syndrome type 1 (Strong), mode of inheritance: AR
• autoimmune lymphoproliferative syndrome type 1 (Limited), mode of inheritance: AD
• autoimmune lymphoproliferative syndrome type 1 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoimmune lymphoproliferative syndrome, type IB	AD	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	8787672; 15004557; 16627752; 17605793; 20301287
Biallelic variants have been described as resulting in more severe presentations, including as relates to autoimmunity and lymphoproliferation

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FASLG gene.

• Autoimmune lymphoproliferative syndrome type 1 (162 variants)
• not provided (11 variants)
• Inborn genetic diseases (8 variants)
• not specified (4 variants)
• Autoimmune lymphoproliferative syndrome type 1;Lung cancer (2 variants)
• Autoimmune lymphoproliferative syndrome, type 1b (1 variants)
• Immunodeficiency 98 with autoinflammation, X-linked (1 variants)
• FASLG-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FASLG 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	35	2	38
missense			64	5		69
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel			11			11
splice donor/acceptor (+/-2bp)						0
splice region			1	2		3
non coding			11	14	13	38
Total	2	0	87	54	15

Variants in FASLG

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

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

Position	Type	Phenotype	Significance	ClinVar
1-172659186-T-C		Autoimmune lymphoproliferative syndrome type 1	Likely benign (Jan 13, 2018)
1-172659232-C-G		not specified	Uncertain significance (Jan 03, 2024)
1-172659243-G-C		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Jan 13, 2018)
1-172659244-GT-G		Autoimmune lymphoproliferative syndrome type 1	Pathogenic (Oct 05, 2023)
1-172659250-A-C		Autoimmune lymphoproliferative syndrome type 1 • FASLG-related disorder	Uncertain significance (Dec 18, 2023)
1-172659252-C-A		not specified	Uncertain significance (May 04, 2022)
1-172659255-T-A		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Mar 28, 2020)
1-172659273-C-A		Autoimmune lymphoproliferative syndrome type 1	Likely benign (Oct 11, 2018)
1-172659292-C-T		Autoimmune lymphoproliferative syndrome type 1 • not specified	Uncertain significance (Nov 07, 2023)
1-172659296-G-C		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Dec 22, 2019)
1-172659309-G-A		Autoimmune lymphoproliferative syndrome type 1 • FASLG-related disorder	Benign/Likely benign (Jan 16, 2024)
1-172659310-C-G		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Aug 28, 2021)
1-172659314-G-A		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Aug 09, 2021)
1-172659318-G-T		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Nov 15, 2021)
1-172659320-C-T		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Jul 28, 2021)
1-172659333-GCCA-G		Autoimmune lymphoproliferative syndrome type 1 • FASLG-related disorder	Conflicting classifications of pathogenicity (Feb 05, 2024)
1-172659333-GCCACCA-G		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (May 20, 2022)
1-172659335-CACCACCACCACCGCCACCGCCACCACT-C		FASLG-related disorder	Uncertain significance (Jan 05, 2024)
1-172659336-A-G		Autoimmune lymphoproliferative syndrome type 1	Likely benign (Dec 11, 2023)
1-172659338-C-T		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Mar 14, 2022)
1-172659339-ACCACCACCG-A		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Sep 05, 2022)
1-172659342-ACCACCG-A		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Aug 27, 2021)
1-172659342-A-ACCACCG		Autoimmune lymphoproliferative syndrome type 1 • FASLG-related disorder	Uncertain significance (Feb 06, 2023)
1-172659345-A-G		Autoimmune lymphoproliferative syndrome type 1	Likely benign (Oct 23, 2023)
1-172659347-C-T		Autoimmune lymphoproliferative syndrome type 1	Uncertain significance (Mar 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FASLG	protein_coding	protein_coding	ENST00000367721	4	7861

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.183	0.806	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.575	135	155	0.870	0.00000788	1819
Missense in Polyphen		26	42.668	0.60935		492
Synonymous	-0.250	66	63.5	1.04	0.00000342	575
Loss of Function	2.20	3	10.8	0.277	5.43e-7	127

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:26334989, PubMed:9228058). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:9228058, PubMed:7528780, PubMed:9427603). Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (By similarity). TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (By similarity). Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (PubMed:27806260). {ECO:0000250|UniProtKB:P41047, ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:27806260, ECO:0000269|PubMed:7528780, ECO:0000269|PubMed:9228058, ECO:0000269|PubMed:9427603}.; FUNCTION: FasL intracellular domain: Cytoplasmic form induces gene transcription inhibition. {ECO:0000269|PubMed:17557115}.
• Disease: DISEASE: Autoimmune lymphoproliferative syndrome 1B (ALPS1B) [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:26334989, ECO:0000269|PubMed:8787672}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Type I diabetes mellitus - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Allograft rejection - Homo sapiens (human);Graft-versus-host disease - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Influenza A - Homo sapiens (human);Autoimmune thyroid disease - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Ras signaling pathway - 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);Apoptosis Modulation and Signaling;Allograft Rejection;Nanomaterial induced apoptosis;Apoptosis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Photodynamic therapy-induced AP-1 survival signaling.;Apoptotic Signaling Pathway;Hepatitis C and Hepatocellular Carcinoma;MAPK Signaling Pathway;Apoptosis Modulation by HSP70;Protein alkylation leading to liver fibrosis;Interleukin-4 and 13 signaling;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;PI3K-Akt Signaling Pathway;Ras Signaling;DNA Damage Response (only ATM dependent);Signal Transduction;il-2 receptor beta chain in t cell activation;akt signaling pathway;pten dependent cell cycle arrest and apoptosis;hiv-1 nef: negative effector of fas and tnf;stress induction of hsp regulation;keratinocyte differentiation;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Fas;GPCR signaling-G alpha q;Regulation of necroptotic cell death;GPCR signaling-cholera toxin;Dimerization of procaspase-8;GPCR signaling-pertussis toxin;Regulation by c-FLIP;Ligand-dependent caspase activation;Caspase activation via extrinsic apoptotic signalling pathway;Immune System;Apoptosis;CASP8 activity is inhibited;Regulated Necrosis;Programmed Cell Death;TNFs bind their physiological receptors;RIPK1-mediated regulated necrosis;fas signaling pathway (cd95);GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;FasL/ CD95L signaling;role of nicotinic acetylcholine receptors in the regulation of apoptosis;JAK STAT pathway and regulation;Death Receptor Signalling;GPCR signaling-G alpha i;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;IL2 signaling events mediated by STAT5;Downstream signaling in naïve CD8+ T cells;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;FAS (CD95) signaling pathway;FoxO family signaling;IL12-mediated signaling events;Calcium signaling in the CD4+ TCR pathway (Consensus)

Recessive Scores

• pRec: 0.848

Intolerance Scores

• loftool: 0.0714
• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.691
• hipred: Y
• hipred_score: 0.628
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.723

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fasl
• Phenotype: vision/eye phenotype; digestive/alimentary 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); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype; neoplasm; 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); hematopoietic system phenotype; reproductive system 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); 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); homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: faslg
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: increased curvature

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;inflammatory cell apoptotic process;immune response;signal transduction;cell-cell signaling;positive regulation of cell population proliferation;extrinsic apoptotic signaling pathway via death domain receptors;regulation of signaling receptor activity;negative regulation of angiogenesis;cytokine-mediated signaling pathway;cellular chloride ion homeostasis;response to lipopolysaccharide;positive regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of neuron apoptotic process;positive regulation of epidermal growth factor receptor signaling pathway;retinal cell programmed cell death;endosomal lumen acidification;T cell apoptotic process;necroptotic process;response to growth factor;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;release of sequestered calcium ion into cytosol by endoplasmic reticulum;positive regulation of endothelial cell apoptotic process
• Cellular component: extracellular region;extracellular space;nucleus;plasma membrane;integral component of plasma membrane;caveola;external side of plasma membrane;lysosomal lumen;perinuclear region of cytoplasm;cytoplasmic vesicle lumen;extracellular exosome
• Molecular function: signaling receptor binding;death receptor binding;cytokine activity;tumor necrosis factor receptor binding;protein binding