Entity Detail — Knowledge Graph Node
This page aggregates everything SciDEX knows about FOXO3: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.
FOXO3 is a gene implicated in neurodegeneration research. Key relationships include: activates, inhibits, associated with. Associated with ALS, Aging, Als. Connected to 480 entities in the SciDEX knowledge graph.
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| Gene Symbol | FOXO3 |
| Protein Type | Transcription Factor |
| Target Class | Transcription Factor |
| Function | FOXO3-targeting drugs modulate the PI3K/Akt/FOXO3 signaling pathway to promote FOXO3 nuclear translocation and transcriptional activity, enhancing autophagy, stress resistance, and apoptosis in can... |
| Mechanism of Action | FOXO3-targeting drugs modulate the PI3K/Akt/FOXO3 signaling pathway to promote FOXO3 nuclear translocation and transcriptional activity, enhancing autophagy, stress resistance, and apoptosis in cancer cells. Indirect activators increase FOXO3 expression or prevent its degradation, thereby amplifying cellular protective responses. |
| Subcellular Localization | ** | Nucleus (active), cytoplasm (inactive) | |
| Druggability | Low (0.42) |
| Clinical Stage | Approved |
| Molecular Weight | 71 kDa |
| Pathways | Akt, Angiogenesis, Apoptosis, Autophagy, Chaperone |
| UniProt ID | O43524 |
| Ensembl ID | ENSG00000118445 |
| GeneCards | FOXO3 |
| Human Protein Atlas | FOXO3 |
| Associated Diseases | Aging, Als, Alzheimer, AUTOPHAGY, Cancer |
| Known Drugs/Compounds | DEFERIPRONE, rapamycin, RAPAMYCIN, Ros, trehalose, TREHALOSE |
| Interactions | AD, AGING, AKT, ALOX15, ALS, ALZHEIMER'S DISEASE |
| SciDEX Target | View Target Profile (7 clinical trials) |
| SciDEX Hypotheses | FOXO3-Longevity Pathway Epigenetic Reprogramming |
| KG Connections | 1004 knowledge graph edges |
| Databases | GeneCardsNCBI GeneHPASTRING |
Knowledge base pages for this entity
flowchart TD
FOXO3(["FOXO3"])
Als["Als"]
Ferroptosis("Ferroptosis")
Mitochondrial_Gene_Expression("Mitochondrial Gene Expression")
h_fd52a7a0["h-fd52a7a0"]
SIRT1(["SIRT1"])
Aging["Aging"]
Cancer["Cancer"]
Tumor["Tumor"]
SLC7A11(["SLC7A11"])
Mitochondrial_Dysfunction("Mitochondrial Dysfunction")
Trifluoperazine{"Trifluoperazine"}
AMPK(["AMPK"])
FOXO3 -->|"activates"| Als
FOXO3 -.->|"inhibits"| Ferroptosis
FOXO3 -->|"regulates"| Mitochondrial_Gene_Expression
h_fd52a7a0 -->|"therapeutic target"| FOXO3
SIRT1 -->|"associated with"| FOXO3
SIRT1 -->|"interacts with"| FOXO3
h_fd52a7a0 -->|"targets gene"| FOXO3
FOXO3 -->|"activates"| Aging
FOXO3 -->|"activates"| Cancer
FOXO3 -->|"activates"| Tumor
FOXO3 -->|"binds"| SLC7A11
FOXO3 -.->|"downregulates"| SLC7A11
FOXO3 -->|"involved in"| Mitochondrial_Dysfunction
Trifluoperazine -->|"activates"| FOXO3
AMPK -->|"activates"| FOXO3
style FOXO3 fill:#006494,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0| Target | Relation | Type | Str |
|---|---|---|---|
| benchmark_ot_ad_answer_key:FOXO3 | data_in | dataset_row | 0.00 |
| ds-83b31ef18d49 | provides_data_for | dataset | 1.00 |
| Als | activates | disease | 0.95 |
| Mitochondrial Gene Expression | regulates | process | 0.90 |
| autophagy | promotes | process | 0.90 |
| Ferroptosis | inhibits | process | 0.90 |
| PINK1/PRKN mediated mitophagy | activates | pathway | 0.90 |
| SLC7A11 | downregulates | gene | 0.85 |
| Tumor | activates | disease | 0.85 |
| Aging | activates | disease | 0.85 |
| SLC7A11 | binds | gene | 0.85 |
| Cancer | activates | disease | 0.85 |
| cellular senescence | prevents | phenotype | 0.85 |
| Mitochondrial Dysfunction | involved_in | process | 0.85 |
| Mitochondrial DNA Copy Number | downregulates | phenotype | 0.85 |
| PINK1 | upregulates | gene | 0.85 |
| Cerebral Ischemia-Reperfusion Injury | protects_against | disease | 0.85 |
| BNIP3 | regulates | protein | 0.80 |
| Mitochondrial DNA | downregulates | biomarker | 0.80 |
| neural stem cells | regulates | cell_type | 0.80 |
| neural stem cells | activates | cell_type | 0.80 |
| autophagy pathway | participates_in | pathway | 0.80 |
| Mitophagy | activates | pathway | 0.80 |
| Autophagy | activates | pathway | 0.80 |
| Apoptosis | activates | pathway | 0.80 |
| Oxidative Stress | activates | pathway | 0.80 |
| APOPTOSIS | activates | gene | 0.80 |
| autophagy_pathway | activates | cellular_pathway | 0.80 |
| HIF1A | interacts_with | protein | 0.75 |
| Ischemia | inhibits | disease | 0.75 |
| NAD+ metabolism | participates_in | pathway | 0.75 |
| Als | regulates | disease | 0.75 |
| AUTOPHAGY | activates | pathway | 0.74 |
| PINK1 | expresses | gene | 0.70 |
| MACROPHAGE | expresses | cell_type | 0.70 |
| GPX4 | expresses | gene | 0.70 |
| MICROGLIA | disrupts | cell_type | 0.70 |
| NEURONS | associated_with | cell_type | 0.70 |
| SIRT1 | expresses | gene | 0.70 |
| TRAF6 | activates | gene | 0.70 |
| ULK1 | activates | gene | 0.70 |
| MICROGLIA | activates | cell_type | 0.70 |
| Autophagy | regulates | pathway | 0.70 |
| autophagy | inhibits | process | 0.70 |
| autophagy | activates | process | 0.70 |
| NEURON | activates | cell_type | 0.70 |
| PARKIN | activates | gene | 0.70 |
| Mitophagy | regulates | pathway | 0.70 |
| SIRT1 | regulates | gene | 0.70 |
| OXIDATIVE STRESS | interacts_with | phenotype | 0.70 |
| Source | Relation | Type | Str |
|---|---|---|---|
| benchmark_ot_ad_answer_key:FOXO3 | data_in | dataset_row | 0.00 |
| ds-83b31ef18d49 | data_in | dataset | 1.00 |
| SIRT3 | deacetylates | gene | 0.95 |
| SIRT1 | phosphorylates | protein | 0.90 |
| SIRT1 | associated_with | gene | 0.90 |
| h-7c3c0f40 | targets | hypothesis | 0.90 |
| h-827a821b | targets_gene | hypothesis | 0.90 |
| SIRT1 | interacts_with | protein | 0.90 |
| SIRT3 | activates | gene | 0.90 |
| h-fd52a7a0 | targets | hypothesis | 0.90 |
| Trifluoperazine | activates | drug | 0.85 |
| TRIFLUOPERAZINE | activates | drug | 0.85 |
| AMPK | activates | gene | 0.81 |
| Ros | activates | compound | 0.80 |
| Nobiletin | downregulates | compound | 0.80 |
| MYO1C | regulates | gene | 0.80 |
| MTOR | associated_with | gene | 0.80 |
| mTOR | associated_with | pathway | 0.80 |
| ATG7 | inhibits | gene | 0.70 |
| ATG7 | expresses | gene | 0.70 |
| CREB | activates | gene | 0.70 |
| AMPK | mediates | gene | 0.70 |
| PI3K | regulates | protein | 0.70 |
| CANCER | inhibits | gene | 0.70 |
| DNMT3A | regulates | gene | 0.70 |
| MITOPHAGY | regulates | gene | 0.70 |
| MITOPHAGY | activates | gene | 0.70 |
| P300 | regulates | gene | 0.70 |
| EXOSOME | activates | organelle | 0.70 |
| PI3K | inhibits | protein | 0.70 |
| PINK1 | activates | gene | 0.70 |
| P62 | regulates | gene | 0.70 |
| AUTOPHAGY | regulates | gene | 0.70 |
| PTEN | regulates | gene | 0.70 |
| TREHALOSE | activates | drug | 0.70 |
| SIRT3 | causes | gene | 0.65 |
| AMPK | phosphorylates | gene | 0.65 |
| ERK | activates | gene | 0.60 |
| OXIDATIVE STRESS | activates | gene | 0.60 |
| AUTOPHAGY | associated_with | gene | 0.60 |
| P53 | inhibits | gene | 0.60 |
| MITOPHAGY | associated_with | gene | 0.60 |
| AND | regulates | gene | 0.60 |
| NIX | regulates | gene | 0.60 |
| OXIDATIVE STRESS | regulates | gene | 0.60 |
| AGING | therapeutic_target | gene | 0.60 |
| MTORC1 | associated_with | gene | 0.60 |
| ROS | regulates | gene | 0.60 |
| AUTOPHAGY-RELATED GENES | associated_with | gene | 0.60 |
| GENES | activates | gene | 0.60 |
Hypotheses where this entity is a therapeutic target
| Hypothesis | Score | Disease | Analysis |
|---|---|---|---|
| NMN Supplementation Restores SIRT1/p66Shc/FOXO3 Epigenetic A | 0.790 | neurodegeneration | epigenetic reprogramming aging neurons |
| FOXO3-Pioneer Factor Complex Stabilizes Heterochromatin Unde | 0.700 | neurodegeneration | Investigate mechanisms of epigenetic rep |
| FOXO3-Longevity Pathway Epigenetic Reprogramming | 0.672 | neurodegeneration | Epigenetic clocks and biological aging i |
Scientific analyses that reference this entity
neurodegeneration | 2026-04-04 | 7 hypotheses Top: 1.000
neurodegeneration | 2026-04-03 | 14 hypotheses Top: 0.803
neurodegeneration | 2026-04-01 | 6 hypotheses Top: 0.710
Experimental studies targeting or related to this entity
| Experiment | Type | Disease | Score | Feasibility | Model | Status | Est. Cost |
|---|---|---|---|---|---|---|---|
| Gandouling protection against brain injury in Wilson's disease via SIR | validation | Hepatolenticular degeneration | 0.900 | 0.00 | TX mice (Wilson's disease mode | proposed | N/A |
| Proposed experiment from debate on Epigenetic clocks and biological ag | falsification | Neurodegeneration | 0.400 | 0.50 | mouse | proposed | $450,000 |
| Exercise-BDNF-Mitophagy Biomarker Study in PD | clinical | Parkinson's Disease | 0.400 | 0.50 | human | proposed | $6,550,000 |
| LRRK2/GBA Mutation Carrier Resilience — Why Some Carriers Never Develo | validation | Parkinson's Disease | 0.400 | 0.50 | human | proposed | $2,730,000 |
| Experiment Design: Metal Ion-Synuclein-Mitochondria Axis in Parkinson' | clinical | Parkinson's Disease | 0.400 | 0.50 | human | proposed | $5,460,000 |
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| Increased mitophagy protects cochlear hair cells from aminoglycoside-induced dam [PMID:35471096] | Zhang Y, Fang Q, Wang H, Qi J, Sun S, Li | Autophagy | 2023 | 1 |
| Fifteen-minute consultation: Therapeutic hypothermia for infants with hypoxic is [PMID:31292147] | Cawley P, Chakkarapani E | Arch Dis Child Educ Pract Ed | 2020 | 1 |
| Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve reg [PMID:30135423] | Sahoo PK, Lee SJ, Jaiswal PB, Alber S, K | Nat Commun | 2018 | 1 |
| EB1 and EB3 regulate microtubule minus end organization and Golgi morphology. [PMID:28814570] | Yang C, Wu J, de Heus C, Grigoriev I, Li | J Cell Biol | 2017 | 1 |
| c-Rel Regulates Inscuteable Gene Expression during Mouse Embryonic Stem Cell Dif [PMID:26694615] | Ishibashi R, Kozuki S, Kamakura S, Sumim | J Biol Chem | 2016 | 1 |
| DRAGO (KIAA0247), a new DNA damage-responsive, p53-inducible gene that cooperate [PMID:24652652] | Polato F, Rusconi P, Zangrossi S, Morell | J Natl Cancer Inst | 2014 | 1 |
| IRF4 addiction in multiple myeloma. [PMID:18568025] | Shaffer AL, Emre NC, Lamy L, Ngo VN, Wri | Nature | 2008 | 1 |
| Guishen-erxian decoction can improve ovarian function in rats with premature ova [PMID:40931880] | Zhong H, He Y, Wang W, Liu Y, Chen D et | Histol Histopathol | 2026 | 0 |
| Metabolic surgery mitigates early kidney injury in obese youth with diabetes by [PMID:41665972] | Naik AS, Alakwaa FM, Nair V, McCown PJ, | J Clin Invest | 2026 | 0 |
| FGF21-Mediated Upregulation of SIRT1 Delays Intervertebral Disc Degeneration by [PMID:41860561] | Wu ZL, Ran R, Xie QQ, Zhang C, Chen YJ e | Aging Cell | 2026 | 0 |
| Kaempferol Mitigates Liver Injury Induced by Copper Toxicity Through the Activat [PMID:41891498] | Xu J, Wan W, Mu H, Gong S, Liu Y et al. | J Biochem Mol Toxicol | 2026 | 0 |
| IL-27-Ucp2-FoxO3 axis mediating the polarization of alternatively activated macr [PMID:41918304] | Ma Y, Gan S, Zheng Y, Kang X, Zhu S | Korean J Pain | 2026 | 0 |
| Dnmt3a-mediated hypermethylation of FoxO3 promotes redox imbalance during osteoc [PMID:40106360] | Zhang W, Li W, Du J, Yang C, Yu L, Yang | Proceedings of the National Ac | 2025 | 0 |
| Mitochondrial dysfunction and aging: multidimensional mechanisms and therapeutic [PMID:40634825] | Wei P, Zhang X, Yan C, Sun S, Chen Z, Li | Biogerontology | 2025 | 0 |
| The multifaceted impact of physical exercise on FoxO signaling pathways. [PMID:40861274] | Liu W, Meng P, Li Z, Shen Y, Meng X, Jin | Frontiers in cell and developm | 2025 | 0 |
| Assessment of the Spatial Distribution of Moisture Content in Granular Material [PMID:31234567] | ["Porzuczek J"] | Sensors (Basel, Switzerland) | 2024 | 0 |
| Banxia Xiexin Decoction Prevents HT22 Cells from High Glucose-induced Neurotoxic [PMID:37608672] | ["Shi Y", "Sheng P", "Guo M", "Chen K", | Current computer-aided drug de | 2024 | 0 |
| Intrapericardial Exosome Therapy Dampens Cardiac Injury via Activating Foxo3. [PMID:36252111] | Zhu D, Liu S, Huang K, Wang Z, Hu S, Li | Circulation research | 2022 | 0 |
| Test-retest reliability for performance-based outcome measures among individuals [PMID:35123456] | ["Sions J", "Donohoe M", "Beisheim-Ryan | BMC musculoskeletal disorders | 2022 | 0 |
| CDK9 inhibition blocks the initiation of PINK1-PRKN-mediated mitophagy by regula [PMID:34890308] | Yao J, Wang J, Xu Y, Guo Q, Sun Y, Liu J | Autophagy | 2022 | 0 |
Multi-agent debates referencing this entity
closed · Rounds: 4 · Score: 0.81 · 2026-04-23
closed · Rounds: 4 · Score: 0.75 · 2026-04-16
closed · Rounds: 4 · Score: 0.93 · 2026-04-06
closed · Rounds: 3 · Score: 0.95 · 2026-04-04
closed · Rounds: 4 · Score: 0.95 · 2026-04-03
Hypotheses and analyses mentioning FOXO3 in their description or question text
No additional research found