FADD Gene - Fas Associated via Death Domain
Key adaptor protein in apoptosis and immune signaling
Gene Information Card
| Symbol | FADD |
|---|---|
| Full Name | Fas Associated via Death Domain |
| Gene Type | protein-coding |
| Chromosomal Location | 11q13.3 |
| NCBI Gene ID | 8772 ncbi.nlm.nih.gov/gene/8772 |
| Ensembl ID | ENSG00000168040 |
| UniProt ID | Q13158 |
| OMIM ID | 602457 |
| HGNC ID | 3573 |
| Aliases | GIG3, MORT1, FADD protein |
Description
The FADD (Fas Associated via Death Domain) gene encodes a death domain-containing adaptor protein that mediates apoptotic signaling through death receptors such as Fas (CD95) and TRAIL receptors. FADD recruits caspase-8 to form the death-inducing signaling complex (DISC), initiating the extrinsic apoptosis pathway. It also plays roles in non-apoptotic processes including cell proliferation, inflammation, and innate immunity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune lymphoproliferative syndrome (ALPS) type 1B | Loss-of-function mutations in FADD impair Fas-mediated apoptosis, leading to defective lymphocyte homeostasis and accumulation of autoreactive cells. | ClinVar, OMIM |
| Head and neck squamous cell carcinoma | FADD gene amplification and overexpression correlate with poor prognosis and resistance to apoptosis. | COSMIC, NCBI |
| Colorectal cancer | FADD mutations and altered expression contribute to tumor progression and chemoresistance. | COSMIC, NCBI |
| Hepatocellular carcinoma | FADD downregulation is associated with evasion of apoptosis and metastasis. | NCBI, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 28.5 | High |
| Spleen | 25.3 | High |
| Bone marrow | 20.1 | High |
| Lung | 12.4 | Medium |
| Liver | 8.7 | Medium |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 35.2 | High expression; used in apoptosis studies |
| HeLa (cervical carcinoma) | 22.8 | Moderate expression |
| HEK293 (embryonic kidney) | 18.5 | Moderate expression |
| MCF7 (breast carcinoma) | 12.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Loss of start codon; likely loss of function |
| c.194C>T (p.Pro65Leu) | Missense | <0.1% | Impaired DISC formation; associated with ALPS |
| c.466G>A (p.Glu156Lys) | Missense | <0.1% | Reduced caspase-8 recruitment |
| Amplification (11q13.3) | Copy number gain | 5-10% in HNSCC | Overexpression; oncogenic |
Mutation functional classification
Loss of Function (LOF)
Missense or nonsense mutations that impair FADD protein expression or disrupt death domain interactions, leading to defective apoptosis and immune dysregulation (e.g., ALPS).
Gain of Function (GOF)
Gene amplification or overexpression in cancers such as head and neck squamous cell carcinoma, promoting cell survival and proliferation.
Dominant Negative (DN)
Certain missense mutations (e.g., p.Pro65Leu) produce a truncated or misfolded protein that interferes with wild-type FADD function in DISC assembly.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Fas signaling pathway (CD95)
• TRAIL signaling pathway
• Extrinsic apoptosis pathway
• Death-inducing signaling complex (DISC) assembly
• NF-kappa B signaling (non-canonical)
Protein Summary
The FADD protein (208 amino acids, ~23 kDa) contains an N-terminal death effector domain (DED) and a C-terminal death domain (DD). Through its DD, FADD binds to the cytoplasmic tail of death receptors (e.g., Fas, TRAIL-R1/R2), and via its DED, it recruits procaspase-8/10 to form the DISC. This triggers caspase-8 autoactivation and downstream executioner caspases, leading to apoptosis. FADD also participates in non-apoptotic functions including regulation of NF-κB, cell cycle, and innate immune responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FADD Knockout HEK293 Cell Line | EDJ-KQ1473 | Human | 8772 | Details Get a Quote |
| FADD Knockout A-549 Cell Line | EDJ-KQ21049 | Human | 8772 | Details Get a Quote |
| FADD Knockout HCT 116 Cell Line | EDJ-KQ21050 | Human | 8772 | Details Get a Quote |
| FADD Knockout HeLa Cell Line | EDJ-KQ21051 | Human | 8772 | Details Get a Quote |
| Fadd Knockout 32D Cell Line | EDJ-KZ231 | Mouse | 14082 | Details Get a Quote |
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