gene

FOXO3

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

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.

1004Connections
3Hypotheses
3Analyses
50Outgoing
50Incoming
5Experiments
5Debates

Summary

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 Info
Gene SymbolFOXO3
Protein TypeTranscription Factor
Target ClassTranscription Factor
FunctionFOXO3-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 ActionFOXO3-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) |
DruggabilityLow (0.42)
Clinical StageApproved
Molecular Weight71 kDa
PathwaysAkt, Angiogenesis, Apoptosis, Autophagy, Chaperone
UniProt IDO43524
Ensembl IDENSG00000118445
GeneCardsFOXO3
Human Protein AtlasFOXO3
Associated DiseasesAging, Als, Alzheimer, AUTOPHAGY, Cancer
Known Drugs/CompoundsDEFERIPRONE, rapamycin, RAPAMYCIN, Ros, trehalose, TREHALOSE
InteractionsAD, AGING, AKT, ALOX15, ALS, ALZHEIMER'S DISEASE
SciDEX TargetView Target Profile (7 clinical trials)
SciDEX HypothesesFOXO3-Longevity Pathway Epigenetic Reprogramming
KG Connections1004 knowledge graph edges
DatabasesGeneCardsNCBI GeneHPASTRING
🧬 3D Structure Comparison — FOXO3 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

2UZK — X-ray / Cryo-EM

🔮 AI Predicted Structure

O43524 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (3)

Knowledge base pages for this entity

Canonical Page

FOXO3 Protein (Forkhead Box O3)

protein · 2053 words

FOXO3 Gene

gene · 1179 words

FOXO3 Protein

protein · 887 words

Pathway Diagram

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

Outgoing (670)

TargetRelationTypeStr
benchmark_ot_ad_answer_key:FOXO3data_indataset_row0.00
ds-83b31ef18d49provides_data_fordataset1.00
Alsactivatesdisease0.95
Mitochondrial Gene Expressionregulatesprocess0.90
autophagypromotesprocess0.90

Incoming (334)

SourceRelationTypeStr
benchmark_ot_ad_answer_key:FOXO3data_indataset_row0.00
ds-83b31ef18d49data_indataset1.00
SIRT3deacetylatesgene0.95
SIRT1phosphorylatesprotein0.90
SIRT1associated_withgene0.90

Targeting Hypotheses (3)

Hypotheses where this entity is a therapeutic target

HypothesisScoreDiseaseAnalysis
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

Mentioning Analyses (3)

Scientific analyses that reference this entity

Senescent cell clearance as neurodegeneration therapy

neurodegeneration | 2026-04-04 | 7 hypotheses Top: 1.000

CRISPR-based therapeutic approaches for neurodegenerative diseases

neurodegeneration | 2026-04-03 | 14 hypotheses Top: 0.803

Epigenetic clocks and biological aging in neurodegeneration

neurodegeneration | 2026-04-01 | 6 hypotheses Top: 0.710

Experiments (5)

Experimental studies targeting or related to this entity

ExperimentTypeDiseaseScoreFeasibilityModelStatusEst. 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

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMIDAuthorsJournalYearCitations
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

Debates (5)

Multi-agent debates referencing this entity

Should metabolic reprogramming via SIRT1/NAD+/PGC-1alpha axis be prioritized to

closed · Rounds: 4 · Score: 0.81 · 2026-04-23

Investigate the therapeutic potential of clearing senescent cells (senolytics) t

closed · Rounds: 4 · Score: 0.75 · 2026-04-16

Epigenetic clocks and biological aging in neurodegeneration

closed · Rounds: 4 · Score: 0.93 · 2026-04-06

Senescent cell clearance as neurodegeneration therapy

closed · Rounds: 3 · Score: 0.95 · 2026-04-04

Evaluate the potential of CRISPR/Cas9 and related gene editing technologies for

closed · Rounds: 4 · Score: 0.95 · 2026-04-03

Related Research

Hypotheses and analyses mentioning FOXO3 in their description or question text

No additional research found