gene

FOXO1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about FOXO1: 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.

1263Connections

1Hypotheses

1Analyses

50Outgoing

50Incoming

8Experiments

1Debates

Summary

Forkhead Box O1 transcription factor - a key regulator of cellular stress response, metabolism, and neuronal survival in neurodegenerative diseases.

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🧬 Gene Info

Gene Symbol	FOXO1
Full Name	Forkhead Box O1
Aliases	Forkhead Box O1 transcription factor
Chromosome	13q14.11
Protein Type	Transcription Factor
Target Class	Transcription Factor
Function	It functions as both an activator and repressor depending on cellular context and interacting partners.
Mechanism of Action	Small molecule modulation of protein-DNA interactions or cofactor binding
Druggability	Medium (0.55)
Clinical Stage	Phase I
Molecular Weight	70 kDa
Amino Acids	655 aa
Exons	4 coding exons
Pathways	PI3K
UniProt ID	Q12778
NCBI Gene ID	2308
Ensembl ID	ENSG00000150907
OMIM	136351
GeneCards	FOXO1
Human Protein Atlas	FOXO1
Associated Diseases	Aging, Als, Alzheimer, Amyotrophic Lateral Sclerosis, Cancer
Known Drugs/Compounds	Cinobufagin, Epigallocatechin gallate, MELATONIN, METFORMIN, rapamycin, RAPAMYCIN
Interactions	ACOX1, Actin, Adiponectin, ADIPOQ, AGING, AKT
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	Transcriptional Autophagy-Lysosome Coupling
KG Connections	1261 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure Comparison — FOXO1 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

3CO6 — X-ray / Cryo-EM

🔮 AI Predicted Structure

Q12778 — AlphaFold

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

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

FOXO1 Gene

gene · 1837 words

→

FOXO1 Protein

protein · 3787 words

→

Pathway Diagram

graph TD
    FOXO1["FOXO1"] -->|"Regulates"| LC3["LC3"]
    FOXO1["FOXO1"] -->|"Associated With"| neurodegeneration["neurodegeneration"]
    FOXO1["FOXO1"] -->|"Activates"| Ms["Ms"]
    FOXO1["FOXO1"] -->|"Activates"| Inflammation["Inflammation"]
    FOXO1["FOXO1"] -->|"Activates"| Fibrosis["Fibrosis"]
    FOXO1["FOXO1"] -->|"Activates"| Cancer["Cancer"]
    FOXO1["FOXO1"] -->|"Associated With"| Als["Als"]
    FOXO1["FOXO1"] -->|"Associated With"| Aging["Aging"]
    h_ae1b2beb["h-ae1b2beb"] -->|"Targets Gene"| FOXO1["FOXO1"]
    BAX["BAX"] -->|"Associated With"| FOXO1["FOXO1"]
    EHMT2["EHMT2"] -->|"Associated With"| FOXO1["FOXO1"]
    JUN["JUN"] -->|"Inhibits"| FOXO1["FOXO1"]
    SOD2["SOD2"] -->|"Activates"| FOXO1["FOXO1"]
    style FOXO1 fill:#8d4900,color:#e0e0e0
    style LC3 fill:#8d4900,color:#e0e0e0
    style neurodegeneration fill:#b71c1c,color:#e0e0e0
    style Ms fill:#b71c1c,color:#e0e0e0
    style Inflammation fill:#b71c1c,color:#e0e0e0
    style Fibrosis fill:#b71c1c,color:#e0e0e0
    style Cancer fill:#b71c1c,color:#e0e0e0
    style Als fill:#b71c1c,color:#e0e0e0
    style Aging fill:#b71c1c,color:#e0e0e0
    style h_ae1b2beb fill:#607D8B,color:#e0e0e0
    style BAX fill:#8d4900,color:#e0e0e0
    style EHMT2 fill:#8d4900,color:#e0e0e0
    style JUN fill:#8d4900,color:#e0e0e0
    style SOD2 fill:#8d4900,color:#e0e0e0

Outgoing (862)

Target	Relation	Type	Str
Als	activates	disease	1.00
Amyotrophic Lateral Sclerosis	mediates	disease	0.95
hepatocyte apoptosis	promotes	process	0.95
Hepatocytes	expressed_in	cell_type	0.95
Liver Fibrosis	protects_against	disease	0.95
ALS	mediates	disease	0.95
Myogenesis	regulates	process	0.95
TGFB1	upregulates	gene	0.92
Myogenesis	inhibits	process	0.92
Tgfb1 Expression	regulates	process	0.91
Hepatic Inflammation	regulates	process	0.90
TGFB1	mediates	protein	0.90
GH1	upregulates	gene	0.90
SOD2	upregulates	gene	0.90
Glucose Metabolism	regulates	process	0.90
CCL4-induced Liver Injury	protects_against	disease	0.90
CAT	upregulates	gene	0.90
Hepatic Stellate Cell Activation	promotes	process	0.90
Hepatic Inflammation	promotes	process	0.90
Reactive Oxygen Species	regulates	process	0.90
Hepatocyte	expressed_in	cell_type	0.90
Liver Fibrosis	regulates	disease	0.90
AKT	activates	gene	0.90
Energy Homeostasis	regulates	process	0.88
Motor Nerve Terminal Dysfunction	inhibits	phenotype	0.88
Ccl4-Induced Liver Injury	contributes_to	phenotype	0.88
Hsc Activation	modulates	process	0.87
Pi3K-Akt Signaling	mediates	pathway	0.85
GH1	binds	gene	0.85
Cancer	regulates	disease	0.85
Glucose Oxidation	regulates	process	0.85
Motor Abnormalities	inhibits	phenotype	0.85
Tumor	activates	disease	0.85
Cancer	activates	disease	0.85
glycogen synthesis	regulates	process	0.85
apoptosis	associated_with	process	0.85
TGF-β1	regulates	protein	0.85
Inflammation	activates	disease	0.85
Diabetes	regulates	disease	0.85
Inflammation	inhibits	process	0.85
Cell Proliferation	regulates	process	0.85
Non-Alcoholic Fatty Liver Disease	regulates	disease	0.82
OPTN	regulates	gene	0.81
ATG	regulates	gene	0.80
Cell Migration	regulates	process	0.80
TGF-β1	regulates	protein	0.80
Cell Invasion	regulates	process	0.80
antioxidant production	promotes	process	0.80
Antioxidant Production	promotes	process	0.80
cell proliferation	suppresses	process	0.80

Incoming (401)

Source	Relation	Type	Str
TAZ	activates	gene	0.95
SDHHQ	modulates	drug	0.90
PI3K/AKT1	inhibits	pathway	0.90
h-ae1b2beb	targets	hypothesis	0.90
cAMP/PKA signaling pathway	upregulates	pathway	0.90
Carbon Tetrachloride	upregulates	compound	0.88
Epigallocatechin gallate	targets	compound	0.85
Cinobufagin	activates	compound	0.85
G9A	regulates	protein	0.85
AKT1	inhibits	protein	0.85
EHMT2	inhibits	gene	0.85
PI3K-Akt Signaling	regulates	pathway	0.85
AKT1	regulates	protein	0.85
YAP1	binds	protein	0.82
Cinobufagin	upregulates	compound	0.80
MTOR	associated_with	gene	0.80
AKT1	phosphorylates	gene	0.80
USP1	interacts_with	gene	0.80
DAPK1	regulates	gene	0.80
G9a	regulates	enzyme	0.80
PI3K	regulates	gene	0.70
Hippo	interacts_with	pathway	0.70
METFORMIN	activates	drug	0.70
INFLAMMATION	activates	gene	0.70
APOPTOSIS	regulates	gene	0.70
MITOCHONDRIAL DYSFUNCTION	activates	gene	0.70
STROKE	activates	disease	0.70
PTEN	regulates	gene	0.70
PTEN	phosphorylates	gene	0.70
PTEN	activates	gene	0.70
APOPTOSIS	activates	gene	0.70
SOD2	activates	gene	0.70
MELATONIN	activates	drug	0.70
HEPATOCYTES	treats	cell_type	0.65
MELATONIN	interacts_with	drug	0.65
MAPK	interacts_with	gene	0.65
ERK1	activates	gene	0.60
SHH	expressed_in	gene	0.60
FOXG1	associated_with	gene	0.60
RANBP2	interacts_with	gene	0.60
FOXP1	associated_with	gene	0.60
FOXM1	associated_with	gene	0.60
FOXP3	associated_with	gene	0.60
FOXO3	associated_with	gene	0.60
MTOR	interacts_with	gene	0.60
FOXO6	associated_with	gene	0.60
CREBBP	regulates	gene	0.60
FOXA2	associated_with	gene	0.60
AKT	activates	gene	0.60
AGING	associated_with	gene	0.60

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Transcriptional Autophagy-Lysosome Coupling	0.882	neurodegeneration	Autophagy-lysosome pathway convergence a

Mentioning Analyses (1)

Scientific analyses that reference this entity

Autophagy-lysosome pathway convergence across neurodegenerative diseases

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.882

Experiments (8)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Autophagy Enhancement Drug Screening for Neurodegeneration	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$6,550,000
Chaperone-Mediated Autophagy Dysfunction in PD - Experiment Design	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Macroautophagy Dysfunction in PD - Experiment Design	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Validate Mitochondria-Lysosome Contact Site Dysfunction in PD	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,730,000
Mutant Huntingtin (mHTT) Clearance Mechanisms — Therapeutic Target Val	validation	Neurodegeneration	0.400	0.50	human	proposed	$3,000,000
MLCS Quantification in Parkinson's Disease	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,730,000
Presymptomatic GRN Carrier Intervention Timing — Biomarker-Guided Ther	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
TMEM106B Haplotype as Genetic Modifier in FTD — Mechanism and Therapeu	validation	Neurodegeneration	0.400	0.50	human	proposed	$2,730,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Hepatocyte FoxO1 Deficiency Protects From Liver Fibrosis via Reducing Inflammati [PMID:37678798]	Pan Q, Gao M, Kim D, Ai W, Yang W, Jiang	Cell Mol Gastroenterol Hepatol	2024	1
Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1. [PMID:37384704]	Zhang T, Xu D, Trefts E, Lv M, Inuzuka H	Science	2023	1
Cinobufagin induces FOXO1-regulated apoptosis, proliferation, migration, and inv [PMID:35176466]	Zhang L, Liang B, Xu H, Gong Y, Hu W, Ji	J Ethnopharmacol	2022	1
Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK [PMID:31693892]	Wang Y, An H, Liu T, Qin C, Sesaki H, Gu	Cell Rep	2019	1
AMPK-Mediated BECN1 Phosphorylation Promotes Ferroptosis by Directly Blocking Sy [PMID:30057310]	Song X, Zhu S, Chen P, Hou W, Wen Q, Liu	Curr Biol	2018	1
Obestatin controls the ubiquitin-proteasome and autophagy-lysosome systems in gl [PMID:28675664]	Cid-Díaz T, Santos-Zas I, González-Sánch	J Cachexia Sarcopenia Muscle	2017	1
PTEN loss drives B7H3 upregulation via the mTORC2/FOXO/c-Myc axis to promote tum [PMID:41920736]	Wang Z, Jin N, Li X, Ma X, Feng Y, Yin K	Cell reports	2026	0
Mammalian lipophagy: process and function. [PMID:41681129]	Zhao R, Dai E, Kang R, Liu J, Klionsky D	Autophagy	2026	0
TAZ alleviates ischemic stroke injury by activating Foxo1: Usp1-mediated deubiqu [PMID:41921828]	["Xin Y", "Sun Y", "Pan E", "Li M", "Che	Free radical biology & medicin	2026	0
Combining network pharmacology and multi-omics reveals the role of Shengdihuang- [PMID:41655545]	Cao X, Shang Y, Qu M, Kang Q, Xu Y et al	Phytomedicine	2026	0
Comparative transcriptomics of adherent and suspension chicken fibroblast cell l [PMID:41763754]	Contreras EJ, Nagarajan A, Bromberg BH,	Food Res Int	2026	0
FOXO1 transcription factor modulates airway epithelial responses to viral infect [PMID:41931532]	Daniel NM, Mann-Nüttel R, Shrestha Palik	PLoS One	2026	0
Effects of Vitamin A Restriction on Carcass Characteristics, Antioxidant Capacit [PMID:41856090]	Zhang X, Zhang C, Song J, Bai J, Hao B,	Animal bioscience	2026	0
Transcriptomic identification of CREB1 and FOXO1 activation in neuregulin-1-medi [PMID:41907189]	Bennett KR, Surles-Zeigler MC, Augello C	Frontiers in molecular neurosc	2026	0
Human MKP-3 isoforms display differential structural and functional profiles. [PMID:41865406]	Mori Sequeiros Garcia MM, Nudler S, Bigi	Biochemical and biophysical re	2026	0
Role of Uncertainty in Illness and Coping Strategies in Advance Directive Comple [PMID:38567890]	["Fuson O", "Mitra A", "Little C", "Hiat	Journal of clinical gastroente	2025	0
The GLP-1 agonist semaglutide ameliorates cognitive regression in P301S tauopath [PMID:39875022]	["Elbadawy N", "Saad M", "Elfarrash S",	European journal of pharmacolo	2025	0
The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkins [PMID:39964974]	Dai L, Wang J, Meng L, Zhang X, Xiao T,	PLoS biology	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
Programmable protein stabilization with language model-derived peptide guides. [PMID:40229275]	["Hong L", "Ye T", "Wang T", "Srijay D",	Nature communications	2025	0

Debates (1)

Multi-agent debates referencing this entity

Multiple NDDs converge on autophagy-lysosome dysfunction. Are there universal th

closed · Rounds: 4 · Score: 0.90 · 2026-04-06

Related Research

Hypotheses and analyses mentioning FOXO1 in their description or question text

No additional research found