FADD

Fas associated via death domain, the group of Death inducing signaling complex |Death effector domain containing|Ripoptosome

Basic information

Region (hg38): 11:70203295-70207390

Links

ENSG00000168040 ∙ NCBI:8772 ∙ OMIM:602457 ∙ HGNC:3573 ∙ Uniprot:Q13158 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the FADD gene.

• FADD-related immunodeficiency (86 variants)
• not provided (7 variants)
• Inborn genetic diseases (4 variants)
• not specified (2 variants)

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			1	32	2	35
missense			49	1		50
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				4	3	7
Total	0	0	50	37	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	Benign (Jan 03, 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	Uncertain significance (Feb 21, 2022)
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: gnomAD

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: dbNSFP

• 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