gene

GPX4

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about GPX4: 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.

2274Connections

7Hypotheses

6Analyses

50Outgoing

50Incoming

3Experiments

6Debates

Summary

GPX4 is a gene implicated in neurodegeneration research. Key relationships include: activates, inhibits, regulates. Associated with ALS, Aging, Als. Connected to 949 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	GPX4
Full Name	Glutathione Peroxidase 4
Chromosome	19p13.3
Protein Type	Enzyme
Target Class	Enzyme
Function	GPX4 serves as the primary defense against lipid peroxidation in cellular membranes
Mechanism of Action	Small molecule inhibitor or activator of peroxidase activity
Subcellular Localization	</strong></td><td>Cytosol, Mitochondria, Nucleus</td></tr>
Druggability	Low (0.41)
Clinical Stage	Phase II
Molecular Weight	22 kDa
Pathways	Akt, Apoptosis, Autophagy, Differentiation, Epigenetic
UniProt ID	P36969
Ensembl ID	ENSG00000167468
GeneCards	GPX4
Human Protein Atlas	GPX4
Associated Diseases	Als, Alzheimer, Cancer, Carcinoma, Copd
Known Drugs/Compounds	curcumin, CURCUMIN, icariin, N-ACETYLCYSTEINE, NICOTINAMIDE, paricalcitol
Interactions	ACETYL-COA, ACHE, ACSL4, ACTB, AD, AGING
SciDEX Target	View Target Profile (10 clinical trials)
SciDEX Hypotheses	Ferroptosis Inhibition for α-Synuclein Neuroprotec GPX4 Selenopeptide Mimetics as Neuroprotective Fer
KG Connections	2268 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — GPX4 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

2OBI — X-ray / Cryo-EM

🔮 AI Predicted Structure

P36969 — 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

Pathway Diagram

graph TD
    GPX4["GPX4"] -->|"associated"| neurodegeneration["neurodegeneration"]
    GPX4["GPX4"] -->|"interacts"| SLC7A11["SLC7A11"]
    GPX4["GPX4"] -->|"co discussed"| PLA2G6["PLA2G6"]
    GPX4["GPX4"] -->|"co discussed"| MMP2["MMP2"]
    GPX4["GPX4"] -->|"co discussed"| C3["C3"]
    GPX4["GPX4"] -->|"co discussed"| PLA2G4A["PLA2G4A"]
    SLC7A11_1["SLC7A11"] -->|"interacts"| GPX4["GPX4"]
    MMP9["MMP9"] -->|"co discussed"| GPX4["GPX4"]
    SLC7A11_2["SLC7A11"] -->|"co discussed"| GPX4["GPX4"]
    AQP4["AQP4"] -->|"co discussed"| GPX4["GPX4"]
    style GPX4 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (1502)

Target	Relation	Type	Str
Tumor	therapeutic_target	disease	1.00
Als	activates	disease	1.00
Cancer	activates	disease	1.00
Als	regulates	disease	1.00
FERROPTOSIS	activates	gene	1.00
CANCER	regulates	gene	1.00
NRF2	activates	gene	1.00
Cancer	inhibits	disease	1.00
FERROPTOSIS	inhibits	pathway	1.00
Ferroptosis	inhibits	pathway	1.00
FERROPTOSIS	regulates	gene	1.00
Cancer	therapeutic_target	disease	1.00
Cancer	regulates	disease	1.00
CANCER	activates	gene	1.00
ROS	activates	gene	1.00
ferroptosis	inhibits	phenotype	1.00
NRF2	inhibits	gene	1.00
Als	inhibits	disease	1.00
ROS	inhibits	gene	1.00
Ferroptosis	activates	pathway	1.00
Tumor	activates	disease	1.00
STING	activates	protein	1.00
Tumor	inhibits	disease	1.00
Ferroptosis	regulates	pathway	1.00
CANCER	inhibits	gene	1.00
CANCER	therapeutic_target	gene	1.00
Oxidative Stress	activates	pathway	1.00
Oxidative Stress	regulates	pathway	1.00
Inflammation	activates	disease	0.95
ferroptosis	participates_in	pathway	0.90
lipid peroxidation	inhibits	phenotype	0.90
Chondrocyte Ferroptosis	inhibits	process	0.90
Lipid Peroxidation	catalyzes	process	0.90
CHRONIC KIDNEY DISEASE	protects_against	disease	0.90
redox homeostasis	regulates	phenotype	0.90
oxidative stress response	participates_in	pathway	0.90
autophagy pathway	participates_in	pathway	0.90
Ferroptosis	associated_with	process	0.90
SLC7A11	associated_with	gene	0.90
ferroptosis	associated_with	process	0.90
Ferroptosis	inhibits	process	0.90
phospholipid hydroperoxides	reduces	mechanism	0.90
TFR1	associated_with	gene	0.90
unfolded protein response	participates_in	pathway	0.90
glutathione-dependent lipid peroxidation	mediates	process	0.90
GENES	inhibits	gene	0.90
Apoptosis	inhibits	pathway	0.90
Oxidative Stress	inhibits	pathway	0.90
APOPTOSIS	activates	gene	0.90
Apoptosis	therapeutic_target	pathway	0.90

Incoming (772)

Source	Relation	Type	Str
TMEM16F	regulates	gene	1.00
SLC7A11	regulates	gene	1.00
SLC7A11	inhibits	gene	1.00
SLC7A11	activates	gene	1.00
NRF2	upregulates	protein	0.95
copper	binds_to	drug	0.95
STING	targets	protein	0.95
FUNDC1	interacts_with	protein	0.95
HNRNPA2B1	associated_with	protein	0.93
Emodin	downregulates	drug	0.92
Lactoferrin	upregulates	protein	0.91
TRIM34	upregulates	gene	0.90
Thonningianin A	activates	chemical	0.90
Rotenone	downregulates	compound	0.90
autophagy	degrades	process	0.90
h-2c776894	targets	hypothesis	0.90
STING	inhibits	protein	0.90
Klebsiella Pneumoniae	downregulates	disease	0.90
TAX1BP1	modulates	protein	0.90
h-7957bb2a	targets	hypothesis	0.90
NFE2L2	upregulates	gene	0.90
ACSL4	associated_with	gene	0.90
GSH	activates	protein	0.90
HSP90	interacts_with	protein	0.90
ZDHHC8	modifies	protein	0.90
MIR130B	upregulates	gene	0.90
AUTOPHAGY	mediates	process	0.89
UBIQUITIN	mediates	entity	0.88
KAEMPFEROL	upregulates	drug	0.88
Ncoa4 Knockdown	upregulates	mechanism	0.88
HSC70	binds	protein	0.87
Hnrnpa2B1	upregulates	protein	0.87
Nonsense-Mediated Decay	regulates	pathway	0.87
Autophagy	mediates	process	0.87
Lactoferrin	correlates_with	protein	0.85
Montelukast	upregulates	drug	0.85
UPF1	regulates	protein	0.85
116B	upregulates	compound	0.85
116B	upregulates	compound	0.85
STING	upstream_of	protein	0.85
copper	upstream_of	drug	0.85
UBIQUITIN	modulates	protein	0.85
Cadmium	downregulates	compound	0.85
INTERLEUKIN-1 BETA	downregulates	protein	0.85
Paricalcitol	upregulates	drug	0.85
Klebsiella pneumoniae	downregulates	disease	0.85
HSP90	promotes	protein	0.85
BDNF	upregulates	gene	0.85
Chronic cerebral hypoperfusion	inhibits	process	0.85
THBS1	associated_with	protein	0.85

Targeting Hypotheses (7)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Sequential Iron Chelation (Deferoxamine) and GPX4 Restoratio	0.838	neurodegeneration	View
SIRT1 Activation Couples Mitochondrial Biogenesis to Ferropt	0.824	neurodegeneration	View
Iron-driven lipid peroxidation and GPX4 failure create a fer	0.750	neurodegeneration	What mechanisms drive the self-amplifyin
Ferroptosis Inhibition for α-Synuclein Neuroprotection	0.705	neurodegeneration	Gene expression changes in aging mouse b
GPX4 Selenopeptide Mimetics as Neuroprotective Ferroptosis B	0.680	-	Ferroptosis in ALS and motor neuron dise

GPX4 Activation as Neuroprotective Strategy	0.550	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
FSP1/CoQ10 Axis as GPX4-Independent Neuroprotective Pathway	0.480	neurodegeneration	Can ferroptosis inhibitors prevent BBB d

Mentioning Analyses (6)

Scientific analyses that reference this entity

Ferroptosis in ALS and motor neuron disease: GPX4, lipid peroxidation, and iron

neurodegeneration | 2026-04-16 | 7 hypotheses Top: 0.680

What determines the GPX4/ACSL4 balance that switches microglia from protective t

immunology | 2026-04-15 | 0 hypotheses

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

neurodegeneration | 2026-04-03 | 44 hypotheses Top: 0.990

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

neurodegeneration | 2026-04-03 | 18 hypotheses Top: 0.847

Mitochondrial transfer between astrocytes and neurons

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.813

Experiments (3)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Irisin effects on osteogenic differentiation in mesenchymal stem cells	exploratory	bone fracture	0.900	mouse bone mesenchymal stem ce	proposed	N/A
S-equol-induced ferroptosis mechanism in TNBC cells	exploratory	Triple negative breast cancer	0.900	TNBC cell lines	proposed	N/A
Gandouling protection against brain injury in Wilson's disease via SIR	validation	Hepatolenticular degeneration	0.900	TX mice (Wilson's disease mode	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
GPX4 promotes optic nerve regeneration and retinal ganglion cell neuroprotection [PMID:41485051]	Yang M, Bian F, Feng X, Li L, Huang H et	Mol Ther	2026
Extracellular GPX4 impairs antitumor immunity via dendritic ZP3 receptors. [PMID:41494530]	Liu J, Cai X, Lin J, Zhang Z, Zhou Q et	Cell	2026
Aging at the Crossroads of Cuproptosis and Ferroptosis: From Molecular Pathways [PMID:41516398]	Gromadzka G, Tarnacka B, Cieślik M	Int J Mol Sci	2026
Ferroptosis in neurological diseases: moving towards therapeutic intervention. [PMID:41554903]	Tuo QZ, Bush AI, Lei P	Mol Psychiatry	2026
Fin(e)-tuning ferroptosis. [PMID:41576911]	Szylo KJ, Dixon SJ	Mol Cell	2026
GPX4-dependent ferroptosis governs ILC2 homeostasis and colitis progression. [PMID:41663525]	Liu G, Wang Y, Huang H, Wang J, Yang J e	Cell Mol Immunol	2026
A GPX1-OSBPL8 axis mediates noncanonical in vivo ferroptosis and cancer growth s [PMID:41720096]	Xia Z, Yang X, Samovich SN, Tyurina YY,	Cell	2026
The crossroads of inflammation and oxidative stress: A review of the interplay b [PMID:41722697]	Park WH	Pharmacol Res	2026
Ferroptosis in Cerebral Ischemia/Reperfusion Injury: Mechanistic Drivers and The [PMID:41738060]	Song C, Liu Z, Tang J, Huang Y	Neuropsychiatr Dis Treat	2026
Decoding GPX4 regulation in ferroptosis: mechanisms and therapeutic implications [PMID:41826143]	Chen X	Trends Mol Med	2026
Montelukast Modulates MPTP-induced Ferroptosis and Neuroinflammation Linked To t [PMID:41712018]	["Jung Yu Jin", "Choi Hyunsu", "Lee Seon	Neuromolecular medicine	2026
A fin-loop-like structure in GPX4 underlies neuroprotection from ferroptosis. [PMID:41349546]	Lorenz SM, Wahida A, Bostock MJ, Seibt T	Cell	2026
Hypoxia-inducible factor-1 as targets for neuroprotection : from ferroptosis to [PMID:39466326]	["Changyong Wang", "Shanyu Lv", "Hongyan	Neurological sciences : offici	2025
Gentiopicroside Attenuated Dopaminergic Neurodegeneration via Inhibiting Neuroin [PMID:40256942]	Unknown	Basic & clinical pharmacol	2025
Astragenol alleviates neuroinflammation and improves Parkinson's symptoms throug [PMID:40306495]	["Shengnan Xiao", "Lianmei Liu", "Xuemei	Journal of ethnopharmacology	2025
Schisanhenol Inhibits MPTP/MPP<sup>+</sup>-Induced Ferroptosis in Dopaminergic N [PMID:41460594]	Unknown	Neurochemical research	2025
Carvedilol Confers Neuroprotective Activity Through Modulating Ferroptosis Key P [PMID:41243756]	Unknown	Journal of biochemical and mol	2025
Betulinic acid protects SH-SY5Y cells exposed to lipopolysaccharide and ferrous [PMID:40985323]	Pandey SK, Singh H, Ahmad S, Singh RK	Free radical research	2025
Neuroprotective role of CHCHD2 in Parkinson's disease: Insights into the GPX4-re [PMID:39566750]	["Wang Fang", "Liu Xuanzhuo", "Chen Ming	Free radical biology & medicin	2025
Granulathiazole A protects 6-OHDA-induced Parkinson's disease from ferroptosis v [PMID:38678778]	Unknown	Bioorganic chemistry	2024

Debates (6)

Multi-agent debates referencing this entity

Ferroptosis in ALS and motor neuron disease: GPX4, lipid peroxidation, and iron

closed · Rounds: 5 · Score: 0.59 · 2026-04-16

While ACSL4-driven ferroptosis was strongly supported, the molecular triggers th

closed · Rounds: 4 · Score: 0.80 · 2026-04-16

Senolytics targeting p16/p21+ senescent astrocytes and microglia may reduce SASP

closed · Rounds: 4 · Score: 0.89 · 2026-04-06

Mitochondrial transfer between astrocytes and neurons

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

What gene expression changes in the aging mouse brain predict neurodegenerative

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

What cell types are most vulnerable in Alzheimers Disease based on SEA-AD transc

closed · Rounds: 4 · Score: 0.90 · 2026-04-03

Related Research

Hypotheses and analyses mentioning GPX4 in their description or question text

GPX4 Activation as Neuroprotective Strategy

Score: 0.550 · neurodegeneration · 2026-04-25

Direct pharmacological activation of GPX4 would inhibit ferroptosis in cerebral microvascular cells, preserving tight ju

FSP1/CoQ10 Axis as GPX4-Independent Neuroprotective Pathway

Score: 0.480 · neurodegeneration · 2026-04-25

FSP1 generates CoQ10 to trap lipid peroxyl radicals at the plasma membrane, providing GPX4-independent protection. Howev

GPX4

Understanding Entity Pages

Summary

Wiki Pages (3)

GPX4 (Glutathione Peroxidase 4)

GPX4 Protein - Glutathione Peroxidase 4

GPX4 Gene - Glutathione Peroxidase 4

Pathway Diagram

Outgoing (1502)

Incoming (772)

Targeting Hypotheses (7)

Mentioning Analyses (6)

Ferroptosis in ALS and motor neuron disease: GPX4, lipid peroxidation, and iron

What determines the GPX4/ACSL4 balance that switches microglia from protective t

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

Mitochondrial transfer between astrocytes and neurons

Senolytic therapy for age-related neurodegeneration

Experiments (3)

Related Papers (20)

Debates (6)

Ferroptosis in ALS and motor neuron disease: GPX4, lipid peroxidation, and iron

While ACSL4-driven ferroptosis was strongly supported, the molecular triggers th

Senolytics targeting p16/p21+ senescent astrocytes and microglia may reduce SASP

Mitochondrial transfer between astrocytes and neurons

What gene expression changes in the aging mouse brain predict neurodegenerative

What cell types are most vulnerable in Alzheimers Disease based on SEA-AD transc

Related Research

GPX4 Activation as Neuroprotective Strategy

FSP1/CoQ10 Axis as GPX4-Independent Neuroprotective Pathway