FASLG
Fas ligand, the group of CD molecules|Tumor necrosis factor superfamily|Death inducing signaling complex
Basic information
Region (hg38): 1:172659103-172666876
Previous symbols: [ "APT1LG1", "TNFSF6" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- Autoimmune lymphoproliferative syndrome type 1 (2 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 | 40 | 43 | ||||
| missense | 69 | 74 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 11 | 11 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 3 | 4 | |||
| non coding | 12 | 18 | 13 | 43 | ||
| Total | 2 | 0 | 93 | 63 | 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 (Aug 24, 2021) | ||
| 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 | Uncertain significance (Aug 23, 2022) | ||
| 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:
| 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:
- 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