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.

2268Connections

8Hypotheses

8Analyses

50Outgoing

50Incoming

4Experiments

9Debates

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.

View on Wiki →

AI-generated illustration · click image to enlarge

Regenerate portrait ↻

🧬 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	GPX4 reserve failure gates selective ALS motor-neu Ferroptosis Inhibition for α-Synuclein Neuroprotec GPX4 Selenopeptide Mimetics as Neuroprotective Fer
KG Connections	2260 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 (1498)

Target	Relation	Type	Str
GPX4	encodes	protein	0.00
FERROPTOSIS	activates	gene	1.00
Ferroptosis	activates	pathway	1.00
NRF2	activates	gene	1.00
STING	activates	protein	1.00
FERROPTOSIS	regulates	gene	1.00
Als	activates	disease	1.00
ferroptosis	NULL	process	1.00
Tumor	activates	disease	1.00
Ferroptosis	regulates	pathway	1.00
Tumor	inhibits	disease	1.00
Ferroptosis	inhibits	pathway	1.00
ROS	activates	gene	1.00
Cancer	inhibits	disease	1.00
CANCER	activates	gene	1.00
CANCER	regulates	gene	1.00
Cancer	therapeutic_target	disease	1.00
Tumor	therapeutic_target	disease	1.00
Als	regulates	disease	1.00
NRF2	inhibits	gene	1.00
Cancer	activates	disease	1.00
Cancer	regulates	disease	1.00
ROS	inhibits	gene	1.00
Als	inhibits	disease	1.00
FERROPTOSIS	inhibits	pathway	1.00
ferroptosis	inhibits	phenotype	1.00
Oxidative Stress	activates	pathway	1.00
Oxidative Stress	regulates	pathway	1.00
CANCER	therapeutic_target	gene	1.00
CANCER	inhibits	gene	1.00
Inflammation	activates	disease	0.95
ferroptosis	participates_in	pathway	0.90
Ferroptosis	associated_with	process	0.90
Ferroptosis	inhibits	process	0.90
CHRONIC KIDNEY DISEASE	protects_against	disease	0.90
ferroptosis	associated_with	process	0.90
TFR1	associated_with	gene	0.90
SLC7A11	associated_with	gene	0.90
phospholipid hydroperoxides	reduces	mechanism	0.90
unfolded protein response	participates_in	pathway	0.90
Lipid Peroxidation	catalyzes	process	0.90
lipid peroxidation	inhibits	phenotype	0.90
redox homeostasis	regulates	phenotype	0.90
Chondrocyte Ferroptosis	inhibits	process	0.90
oxidative stress response	participates_in	pathway	0.90
autophagy pathway	participates_in	pathway	0.90
glutathione-dependent lipid peroxidation	mediates	process	0.90
APOPTOSIS	activates	gene	0.90
OXIDATIVE STRESS	inhibits	gene	0.90
FERROPTOSIS	treats	gene	0.90

Incoming (770)

Source	Relation	Type	Str
GPX4	encodes	gene	0.00
TMEM16F	regulates	gene	1.00
SLC7A11	activates	gene	1.00
SLC7A11	inhibits	gene	1.00
SLC7A11	regulates	gene	1.00
STING	targets	protein	0.95
copper	binds_to	drug	0.95
NRF2	upregulates	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
Rotenone	downregulates	compound	0.90
34145375	suppresses	paper	0.90
ACSL4	associated_with	gene	0.90
h-7957bb2a	targets	hypothesis	0.90
NFE2L2	upregulates	gene	0.90
Klebsiella Pneumoniae	downregulates	disease	0.90
TAX1BP1	modulates	protein	0.90
ZDHHC8	modifies	protein	0.90
MIR130B	upregulates	gene	0.90
autophagy	degrades	process	0.90
HSP90	interacts_with	protein	0.90
STING	inhibits	protein	0.90
TRIM34	upregulates	gene	0.90
h-2c776894	targets	hypothesis	0.90
GSH	activates	protein	0.90
Thonningianin A	activates	chemical	0.90
AUTOPHAGY	mediates	process	0.89
Ncoa4 Knockdown	upregulates	mechanism	0.88
UBIQUITIN	mediates	entity	0.88
KAEMPFEROL	upregulates	drug	0.88
Autophagy	mediates	process	0.87
Hnrnpa2B1	upregulates	protein	0.87
HSC70	binds	protein	0.87
Nonsense-Mediated Decay	regulates	pathway	0.87
UPF1	regulates	protein	0.85
Lactoferrin	correlates_with	protein	0.85
Mitophagy	associated_with	process	0.85
INTERLEUKIN-1 BETA	downregulates	protein	0.85
Montelukast	upregulates	drug	0.85
copper	upstream_of	drug	0.85
Paricalcitol	upregulates	drug	0.85
UBIQUITIN	modulates	protein	0.85
HSP90	promotes	protein	0.85
Klebsiella pneumoniae	downregulates	disease	0.85
Cadmium	downregulates	compound	0.85
Chronic cerebral hypoperfusion	inhibits	process	0.85
STING	upstream_of	protein	0.85
BDNF	upregulates	gene	0.85

Targeting Hypotheses (8)

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
GPX4 reserve failure gates selective ALS motor-neuron ferrop	0.745	neurodegeneration	Ferroptosis in ALS motor neuron vulnerab
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 (8)

Scientific analyses that reference this entity

Ferroptosis in ALS motor neuron vulnerability

neurodegeneration | 2026-04-26 | 3 hypotheses Top: 0.745

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 | 43 hypotheses Top: 0.914

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

neurodegeneration | 2026-04-03 | 0 hypotheses

Experiments (4)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Irisin effects on osteogenic differentiation in mesenchymal stem cells	exploratory	bone fracture	0.900	0.00	mouse bone mesenchymal stem ce	proposed	N/A
S-equol-induced ferroptosis mechanism in TNBC cells	exploratory	Triple negative breast cancer	0.900	0.00	TNBC cell lines	proposed	N/A
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
Sequential DFO + Sulforaphane Prevents Iron-Ferroptosis Cascade in Rat	in_vivo	post-cardiac-arrest neurodegen	0.768	0.72	Sprague-Dawley rat asphyxial c	proposed	$48,000

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
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025
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
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025