FADD Gene

Name	Fas (TNFRSF6)-associated via death domain
Description	The protein encoded by this gene is an adaptor molecule that interacts with various cell surface receptors and mediates cell apoptotic signals. Through its C-terminal death domain, this protein can be recruited by TNFRSF6/Fas-receptor, tumor necrosis factor receptor, TNFRSF25, and TNFSF10/TRAIL-receptor, and thus it participates in the death signaling initiated by these receptors. Interaction of this protein with the receptors unmasks the N-terminal effector domain of this protein, which allows it to recruit caspase-8, and thereby activate the cysteine protease cascade. Knockout studies in mice also suggest the importance of this protein in early T cell development. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FADD (Fas‐associated death domain protein) is a pivotal adaptor molecule that links death receptor activation to downstream caspase‐8 activation, thereby initiating the extrinsic apoptotic pathway. In response to signals from receptors such as TNFR1, Fas, and TRAIL‐R, FADD is recruited into membrane‐bound complexes that subsequently transition into cytoplasmic death‐inducing signaling complexes (DISCs) to trigger caspase‐8 activation and apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its classical role in mediating receptor‐induced apoptosis, FADD is essential for maintaining cellular homeostasis by modulating non‐apoptotic cell death pathways. For example, in lymphocytes and embryonic cells, the absence of FADD results in aberrant accumulation of RIP1 and subsequent activation of necrotic cell death pathways; conversely, concurrent loss of both FADD and RIP1 can restore normal development, underscoring a critical interplay between these molecules."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n FADD also functions in non‐canonical death processes. It cooperates with autophagy‐related proteins such as Atg5 on autophagosomal membranes to form intracellular platforms that promote caspase‐8 self‐association and activation, thus linking autophagic signaling to apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, in neuronal contexts, FADD is an integral component of Fas‐triggered death cascades that involve additional mediators, thereby contributing to selective neuronal cell loss, which may be relevant in neurodegenerative conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, during viral infection and pathogen‐induced stress, FADD is recruited into complexes with RIPK1 and RIPK3 that drive both apoptotic and necroptotic outcomes. In these settings, FADD helps to mediate the balance between cell survival and death, a process that is essential for proper antiviral immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Altogether, FADD is not only critical for the execution of extrinsic apoptosis but also serves as a key regulator that prevents inappropriate necrosis, thereby ensuring immune homeostasis and tissue integrity.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Olivier Micheau, Jürg Tschopp "}, {"type": "b", "children": [{"type": "t", "text": "Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(03)00521-x"}], "href": "https://doi.org/10.1016/s0092-8674(03"}, {"type": "t", "text": "00521-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12887920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12887920"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lai Wang, Fenghe Du, Xiaodong Wang "}, {"type": "b", "children": [{"type": "t", "text": "TNF-alpha induces two distinct caspase-8 activation pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2008.03.036"}], "href": "https://doi.org/10.1016/j.cell.2008.03.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18485876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18485876"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sanjeev Mariathasan, Kim Newton, Denise M Monack, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature02664"}], "href": "https://doi.org/10.1038/nature02664"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15190255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15190255"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "M R Sprick, M A Weigand, E Rieser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1074-7613(00)80211-3"}], "href": "https://doi.org/10.1016/s1074-7613(00"}, {"type": "t", "text": "80211-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10894160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10894160"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haibing Zhang, Xiaohui Zhou, Thomas McQuade, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional complementation between FADD and RIP1 in embryos and lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09878"}], "href": "https://doi.org/10.1038/nature09878"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21368761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21368761"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marius Dannappel, Katerina Vlantis, Snehlata Kumari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature13608"}], "href": "https://doi.org/10.1038/nature13608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25132550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25132550"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jong-Ok Pyo, Mi-Hee Jang, Yun-Kyung Kwon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M413934200"}], "href": "https://doi.org/10.1074/jbc.M413934200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15778222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15778222"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Megan M Young, Yoshinori Takahashi, Osman Khan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.309104"}], "href": "https://doi.org/10.1074/jbc.M111.309104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22362782"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22362782"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Cédric Raoul, Alvaro G Estévez, Hiroshi Nishimune, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0896-6273(02)00905-4"}], "href": "https://doi.org/10.1016/s0896-6273(02"}, {"type": "t", "text": "00905-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12354397"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12354397"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Roshan J Thapa, Justin P Ingram, Katherine B Ragan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2016.09.014"}], "href": "https://doi.org/10.1016/j.chom.2016.09.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27746097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27746097"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Shoko Nogusa, Roshan J Thapa, Christopher P Dillon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RIPK3 Activates Parallel Pathways of MLKL-Driven Necroptosis and FADD-Mediated Apoptosis to Protect against Influenza A Virus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Host Microbe (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chom.2016.05.011"}], "href": "https://doi.org/10.1016/j.chom.2016.05.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27321907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27321907"}]}]}]}
Synonyms	GIG3, MORT1
Proteins	FADD_HUMAN
NCBI Gene ID	8772
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FADD has 12,127 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 129 datasets.

Click the + buttons to view associations for FADD from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FADD Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of FADD gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of FADD gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of FADD gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of FADD gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of FADD gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving FADD protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of FADD gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of FADD gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of FADD gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of FADD gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of FADD gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with FADD gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with FADD protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of FADD gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FADD gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of FADD gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of FADD gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FADD protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing FADD protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing FADD protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with FADD protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with FADD protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing FADD protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of FADD gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FADD gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FADD gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FADD gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of FADD protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by FADD gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving FADD gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with FADD gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with FADD gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with FADD gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with FADD gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FADD gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at FADD gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of FADD gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of FADD gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing FADD from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with FADD gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.