FADD
Fas associated via death domain, the group of Death inducing signaling complex |Death effector domain containing|Ripoptosome
Basic information
Region (hg38): 11:70203296-70207390
Links
Phenotypes
GenCC
Source:
- FADD-related immunodeficiency (Limited), mode of inheritance: AR
- FADD-related immunodeficiency (Supportive), mode of inheritance: AR
- FADD-related immunodeficiency (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 90 with encephalopathy, functional hyposplenia, and hepatic dysfunction | AR | Allergy/Immunology/Infectious; Cardiovascular | Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Patients suffer from stereotypical episodes of fever, liver dyfunction, and encephalopathy, which may be severe and precipitated by viral infections; Other findings, such as cardiovascular malformations, and functional hyposplenism, have been described, and awareness may enable management | Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Neurologic | 21109225 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FADD 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 | 46 | 49 | ||||
| missense | 50 | 51 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 2 | 2 | ||||
| non coding | 10 | |||||
| Total | 0 | 0 | 51 | 54 | 5 |
Variants in FADD
This is a list of pathogenic ClinVar variants found in the FADD region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 11-70203417-A-G | not specified | Benign (Nov 12, 2023) | ||
| 11-70203465-C-T | FADD-related immunodeficiency | Likely benign (Nov 26, 2022) | ||
| 11-70203467-C-G | FADD-related immunodeficiency | Uncertain significance (Sep 01, 2021) | ||
| 11-70203468-G-A | FADD-related immunodeficiency | Likely benign (Oct 24, 2023) | ||
| 11-70203468-G-T | FADD-related immunodeficiency • not specified | Benign/Likely benign (May 20, 2024) | ||
| 11-70203480-G-C | FADD-related immunodeficiency | Likely benign (Jan 04, 2024) | ||
| 11-70203489-G-T | FADD-related immunodeficiency | Likely benign (Feb 15, 2023) | ||
| 11-70203490-G-A | FADD-related immunodeficiency | Uncertain significance (Feb 26, 2018) | ||
| 11-70203505-TCGAGCAG-T | FADD-related immunodeficiency | Pathogenic (Nov 30, 2021) | ||
| 11-70203507-G-A | FADD-related immunodeficiency | Likely benign (Nov 03, 2023) | ||
| 11-70203510-C-G | FADD-related immunodeficiency | Uncertain significance (Nov 15, 2019) | ||
| 11-70203511-A-C | FADD-related immunodeficiency • Inborn genetic diseases | Uncertain significance (Mar 25, 2024) | ||
| 11-70203511-A-G | FADD-related immunodeficiency | Uncertain significance (Jan 28, 2022) | ||
| 11-70203525-G-A | FADD-related immunodeficiency | Likely benign (Mar 20, 2023) | ||
| 11-70203531-G-A | FADD-related immunodeficiency | Likely benign (Jul 02, 2021) | ||
| 11-70203535-C-T | FADD-related immunodeficiency | Likely benign (Apr 28, 2023) | ||
| 11-70203537-A-G | FADD-related immunodeficiency | Likely benign (Dec 01, 2023) | ||
| 11-70203540-C-T | FADD-related immunodeficiency | Likely benign (Dec 31, 2023) | ||
| 11-70203546-G-A | FADD-related immunodeficiency | Likely benign (May 06, 2022) | ||
| 11-70203548-G-C | FADD-related immunodeficiency | Uncertain significance (Mar 26, 2020) | ||
| 11-70203552-G-T | FADD-related immunodeficiency | Benign (Jan 18, 2024) | ||
| 11-70203568-G-A | FADD-related immunodeficiency | Uncertain significance (Jun 16, 2022) | ||
| 11-70203570-G-A | FADD-related immunodeficiency | Likely benign (Jun 25, 2019) | ||
| 11-70203582-C-T | FADD-related immunodeficiency | Likely benign (Aug 28, 2023) | ||
| 11-70203591-C-T | FADD-related immunodeficiency | Likely benign (May 20, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FADD | protein_coding | protein_coding | ENST00000301838 | 2 | 4228 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.526 | 0.417 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.837 | 101 | 128 | 0.791 | 0.00000707 | 1333 |
| Missense in Polyphen | 39 | 48.257 | 0.80818 | 468 | ||
| Synonymous | -1.10 | 70 | 59.3 | 1.18 | 0.00000332 | 450 |
| Loss of Function | 1.37 | 0 | 2.17 | 0.00 | 9.29e-8 | 28 |
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) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling. {ECO:0000269|PubMed:16762833, ECO:0000269|PubMed:19118384, ECO:0000269|PubMed:20935634, ECO:0000269|PubMed:21109225}.;
- Disease
- DISEASE: Infections, recurrent, associated with encephalopathy, hepatic dysfunction and cardiovascular malformations (IEHDCM) [MIM:613759]: A condition with biological features of autoimmune lymphoproliferative syndrome such as high-circulating CD4(-)CD8(-)TCR-alpha-beta(+) T-cell counts, and elevated IL10 and FASL levels. Affected individuals suffer from recurrent, stereotypical episodes of fever, encephalopathy, and mild liver dysfunction sometimes accompanied by generalized seizures. The episodes can be triggered by varicella zoster virus (VZV), measles mumps rubella (MMR) attenuated vaccine, parainfluenza virus, and Epstein-Barr virus (EBV). {ECO:0000269|PubMed:21109225}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Apoptosis - multiple species - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Apoptosis - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Apoptosis Modulation and Signaling;Integrated Breast Cancer Pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Alzheimers Disease;TNF alpha Signaling Pathway;Nanomaterial induced apoptosis;Nanoparticle triggered regulated necrosis;Apoptosis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Apoptotic Signaling Pathway;Apoptosis Modulation by HSP70;RIG-I-like Receptor Signaling;VEGFA-VEGFR2 Signaling Pathway;Toll-like Receptor Signaling Pathway;TWEAK;Signal Transduction;tnfr1 signaling pathway;induction of apoptosis through dr3 and dr4/5 death receptors;hiv-1 nef: negative effector of fas and tnf;nf-kb signaling pathway;Toll Like Receptor 3 (TLR3) Cascade;Toll-Like Receptors Cascades;Fas;NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Regulation of necroptotic cell death;Dimerization of procaspase-8;Regulation by c-FLIP;Ligand-dependent caspase activation;Caspase activation via extrinsic apoptotic signalling pathway;Innate Immune System;Immune System;Apoptosis;CASP8 activity is inhibited;Regulated Necrosis;Programmed Cell Death;RIPK1-mediated regulated necrosis;fas signaling pathway (cd95);ceramide signaling pathway;FasL/ CD95L signaling;TNFR1-induced proapoptotic signaling;TNF signaling;TRAIL signaling;TLR3-mediated TICAM1-dependent programmed cell death;Death Receptor Signalling;TNFalpha;TRIF-mediated programmed cell death;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;TNF;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;TRAIL signaling pathway;TNF receptor signaling pathway ;FAS (CD95) signaling pathway;Ceramide signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.501
Intolerance Scores
- loftool
- 0.0618
- rvis_EVS
- 0.06
- rvis_percentile_EVS
- 58.26
Haploinsufficiency Scores
- pHI
- 0.0643
- hipred
- Y
- hipred_score
- 0.672
- ghis
- 0.553
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.582
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fadd
- 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); 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); embryo phenotype; liver/biliary system phenotype; immune system phenotype; skeleton 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); digestive/alimentary phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype;
Zebrafish Information Network
- Gene name
- fadd
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- kidney development;positive regulation of T cell mediated cytotoxicity;positive regulation of adaptive immune response;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;cell surface receptor signaling pathway;extrinsic apoptotic signaling pathway via death domain receptors;viral process;positive regulation of interferon-gamma production;positive regulation of interleukin-8 production;positive regulation of tumor necrosis factor production;T cell differentiation in thymus;toll-like receptor 3 signaling pathway;TRIF-dependent toll-like receptor signaling pathway;TRAIL-activated apoptotic signaling pathway;positive regulation of activated T cell proliferation;T cell homeostasis;positive regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;response to morphine;innate immune response;positive regulation of macrophage differentiation;positive regulation of proteolysis;positive regulation of transcription by RNA polymerase II;behavioral response to cocaine;lymph node development;spleen development;thymus development;defense response to virus;positive regulation of type I interferon-mediated signaling pathway;negative regulation of necroptotic process;negative regulation of activation-induced cell death of T cells;cellular response to mechanical stimulus;death-inducing signaling complex assembly;motor neuron apoptotic process;apoptotic signaling pathway;extrinsic apoptotic signaling pathway;extrinsic apoptotic signaling pathway in absence of ligand;activation of cysteine-type endopeptidase activity;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 extrinsic apoptotic signaling pathway via death domain receptors;positive regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation;positive regulation of extrinsic apoptotic signaling pathway
- Cellular component
- nucleus;cytoplasm;cytosol;plasma membrane;death-inducing signaling complex;CD95 death-inducing signaling complex;neuron projection;cell body;membrane raft;ripoptosome
- Molecular function
- protease binding;death receptor binding;tumor necrosis factor receptor binding;protein binding;tumor necrosis factor receptor superfamily binding;receptor serine/threonine kinase binding;death effector domain binding;identical protein binding;protein-containing complex binding;caspase binding