gene

ACSL4

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about ACSL4: 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.

747Connections

4Hypotheses

4Analyses

50Outgoing

50Incoming

4Experiments

4Debates

Summary

ACSL4 is a gene implicated in neurodegeneration research. Key relationships include: inhibits, regulates, activates. Associated with ALS, Als, Alzheimer. Connected to 288 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	ACSL4
Full Name	Acyl-CoA Synthetase Long Chain Family Member 4
Chromosome	Xq22.3
Protein Type	Synthetase
Target Class	Enzyme
Function	is an important component in the neurobiology of neurodegenerative diseases.
Mechanism of Action	Enzyme inhibition — blocking ACSL4 prevents incorporation of PUFAs into membrane phospholipids, reducing ferroptosis susceptibility
Primary Expression	various neural cell types:
Druggability	Low (0.41)
Clinical Stage	Phase III
Pathways	Autophagy, Cholesterol, Epigenetic, Ferroptosis, Inflammasome
UniProt ID	[O60488](https://www.uniprot.org/uniprot/O60488)
Ensembl ID	ENSG00000068366
GeneCards	ACSL4
Human Protein Atlas	ACSL4
Associated Diseases	ALS, alzheimer_s_disease, Alzheimer's Disease, CANCER, Carcinoma, Fibrosis
Known Drugs/Compounds	Calycosin, curcumin, CURCUMIN, metformin, METFORMIN, PIOGLITAZONE
Interactions	AKT, ALOX12, ALOX15, ALOX5, ALZHEIMER, ALZHEIMER'S DISEASE
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	ACSL4-Driven Ferroptotic Priming in Disease-Associ 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferro ACSL4-Ferroptotic Priming in Stressed Oligodendroc (+1 more)
KG Connections	746 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

Wiki Pages (3)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    ACSL4["ACSL4"] -->|"activates"| FERROPTOSIS["FERROPTOSIS"]
    ACSL4["ACSL4"] -->|"activates"| LIPID_PEROXIDATION["LIPID_PEROXIDATION"]
    ACSL4["ACSL4"] -->|"associated"| MS["MS"]
    ACSL4["ACSL4"] -->|"therapeutic target"| Als["Als"]
    ACSL4["ACSL4"] -->|"therapeutic target"| Carcinoma["Carcinoma"]
    ACSL4["ACSL4"] -->|"therapeutic target"| Autoimmune["Autoimmune"]
    TMEM16F["TMEM16F"] -->|"regulates"| ACSL4["ACSL4"]
    MIR130B3P["MIR130B3P"] -.->|"inhibits"| ACSL4["ACSL4"]
    SLC7A11["SLC7A11"] -->|"therapeutic target"| ACSL4["ACSL4"]
    MYC["MYC"] -->|"regulates"| ACSL4["ACSL4"]
    style ACSL4 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (538)

Target	Relation	Type	Str
FERROPTOSIS	activates	phenotype	1.00
Ferroptosis	mediates	process	0.95
Fibrosis	associated_with	disease	0.90
oxidative stress response	participates_in	pathway	0.90
Ferroptosis	associated_with	process	0.90
FERROPTOSIS	associated_with	process	0.90
GPX4	associated_with	gene	0.90
Fatty acid activation	catalyzes	mechanism	0.90
PHOSPHATIDYLETHANOLAMINE	acylates	lipid	0.90
ARACHIDONIC_ACID	activates	lipid	0.90
Ferroptosis	activates	pathway	0.90
ferroptosis	mediates	process	0.85
Alzheimer's Disease	associated_with	disease	0.82
ferroptosis	participates_in	pathway	0.82
ferroptosis	associated_with	process	0.80
SLC7A11	associated_with	gene	0.80
MICROGLIA	upregulated_in	cell_type	0.80
LIPROXSTATIN-1	pathway_target_of	drug	0.80
ROSIGLITAZONE	associated_with	drug	0.75
Neurodegeneration	activates	disease	0.75
Tumor	inhibits	disease	0.75
Multiple Sclerosis	associated_with	disease	0.75
LIPID_PEROXIDATION	activates	phenotype	0.72
MICROGLIA	protects_against	cell_type	0.70
unfolded protein response	participates_in	pathway	0.70
MICROGLIA	activates	cell_type	0.70
DIABETES	inhibits	disease	0.70
autophagy pathway	participates_in	pathway	0.70
DEMENTIA	interacts_with	disease	0.70
MICROGLIA	regulates	cell_type	0.70
GPX4	regulates	gene	0.70
FERROPTOSIS	inhibits	gene	0.70
Glycolysis	activates	pathway	0.70
GPX4	inhibits	gene	0.70
MS	associated_with	disease	0.70
Ferroptosis susceptibility	modulates	mechanism	0.70
PYROPTOSIS	inhibits	gene	0.70
Apoptosis	activates	pathway	0.70
GENES	activates	gene	0.70
Ferroptosis	inhibits	pathway	0.70
GSDMD	inhibits	gene	0.70
TNF	inhibits	gene	0.70
Pyroptosis	inhibits	pathway	0.70
MYC	regulates	gene	0.70
Sepsis	activates	disease	0.65
Als	therapeutic_target	disease	0.65
Carcinoma	therapeutic_target	disease	0.65
Autoimmune	therapeutic_target	disease	0.65
Ms	therapeutic_target	disease	0.65
Cancer	regulates	disease	0.65

Incoming (209)

Source	Relation	Type	Str
TMEM16F	regulates	gene	1.00
MIR130B	downregulates	gene	0.95
genes-acsl4	describes	wiki_page	0.95
MIR130B	inhibits	gene	0.95
h-seaad-v4-26ba859b	targets	hypothesis	0.90
Calycosin	binds	compound	0.90
h-var-f96e38ec20	targets_gene	hypothesis	0.90
h-var-22c38d11cd	targets_gene	hypothesis	0.90
h-var-261452bfb4	targets_gene	hypothesis	0.90
Liproxstatin-1	downregulates	drug	0.85
Montelukast	downregulates	drug	0.85
Cadmium	upregulates	compound	0.80
MIR130B3P	inhibits	gene	0.72
SLC7A11	regulates	gene	0.70
PIOGLITAZONE	inhibits	drug	0.70
JNK	associated_with	gene	0.70
LPS	induces	drug	0.70
ATF4	activates	protein	0.70
LIPID PEROXIDATION	regulates	phenotype	0.65
LIPID PEROXIDATION	activates	phenotype	0.65
FERROPTOSIS	targets	phenotype	0.65
MTOR SIGNALING	targets	pathway	0.65
METFORMIN	treats	drug	0.65
MTOR	targets	gene	0.65
CURCUMIN	regulates	drug	0.65
METFORMIN	activates	drug	0.65
ALOX12	inhibits	gene	0.60
PYROPTOSIS	therapeutic_target	gene	0.60
INFLAMMATION	inhibits	gene	0.60
AND	expressed_in	gene	0.60
OXIDATIVE STRESS	interacts_with	gene	0.60
CHAC1	expressed_in	gene	0.60
INSULIN RESISTANCE	inhibits	gene	0.60
CANCER	regulates	gene	0.60
AND	regulates	gene	0.60
GPX4	inhibits	gene	0.60
CPT1A	inhibits	gene	0.60
AND	associated_with	gene	0.60
GPX4	regulates	gene	0.60
GPX4/SLC7A11	regulates	gene	0.60
NRF2	regulates	gene	0.60
MIRNAS	inhibits	gene	0.60
APOPTOSIS	inhibits	gene	0.60
ROS	inhibits	gene	0.60
TNF-Α	inhibits	gene	0.60
GENES	inhibits	gene	0.60
SLC7A11	expressed_in	gene	0.60
TFR1	inhibits	gene	0.60
FTH1	inhibits	gene	0.60
GPX4/SLC7A11	therapeutic_target	gene	0.60

Targeting Hypotheses (4)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
ACSL4-Driven Ferroptotic Priming in Disease-Associated Micro	0.847	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drive	0.801	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Pri	0.801	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligo	0.779	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di

Mentioning Analyses (4)

Scientific analyses that reference this entity

Experiments (4)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
SAHA@LIPO-ANG2 therapeutic efficacy in 5xFAD mice	validation	Alzheimer's disease	0.900	5xFAD transgenic mice	proposed	N/A
Transcriptomic profiling and differential expression analysis	exploratory	Alzheimer's disease	0.900	1-month-old APP/PS1 mice cereb	proposed	N/A
SIRPα modulation in mouse models of Alzheimer's disease	validation	Alzheimer's disease	0.900	mouse models of Alzheimer's di	proposed	N/A
Microglial SIRPα expression in human Alzheimer's disease tissue	exploratory	Alzheimer's disease	0.800	human brain tissue	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Transcriptomic cytoarchitecture reveals principles of human neocortex organizati [PMID:37824655]	Jorstad NL, Close J, Johansen N, Yanny A	Science	2023	186
FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression. [PMID:41862445]	Qin J, Ma S, Wang J, Huang S, Luan J, He	Cell death & disease	2026	0
Quercetin attenuates ox-LDL-induced endothelial injury by regulating ferroptosis [PMID:41902795]	Gao C, Liu B, Zhang R, Tian J, Xin H	Toxicology mechanisms and meth	2026	0
NEDD8 promotes the ferritinophagy and ferroptosis of neurons in ischemic stroke [PMID:41662890]	Rao W, Huang Y, Li J, Chen Q, Sun J et a	J Stroke Cerebrovasc Dis	2026	0
Inhibition of Ferroptosis in Prostatitis Model by Low Intensity Extracorporeal S [PMID:41714892]	Lin D, Li K, Kuang W, Chen Z, Zhang M	World J Mens Health	2026	0
Deciphering sorafenib resistance in hepatocellular carcinoma via ferroptotic mec [PMID:41763496]	Che L, Zhu L, Zhou L, Zhou Y	Biochim Biophys Acta Rev Cance	2026	0
B4GALT1 deficiency attenuates steatohepatitis by regulating the PPARγ/ACSL4 axis [PMID:41860570]	Chien Y, Xia R, Zhou D, Ai Y, Wu L et al	Hepatol Commun	2026	0
Unraveling the impact of risk factors on the ferroptosis-Alzheimer's disease lin [PMID:41498558]	Singh P, Rath SL	Journal of Alzheimer's disease	2026	0
Resveratrol Alleviates Intervertebral Disc Degeneration by Targeting NCOA4-Media [PMID:41873334]	Song C, Wu X, Chen C, Shen B, He Y, Liu	Drug design, development and t	2026	0
Pan-PPAR agonist bezafibrate alleviates psoriasis by suppressing LCN2-dependent [PMID:41662914]	["Xin R", "Zhang J", "Zhang Y", "Dai M",	Free radical biology & medicin	2026	0
Acteoside alleviates sepsis-induced acute lung injury by activating the Nrf2 pat [PMID:41895086]	Wang Y, Zhang W, Zhang M, Zhu Y, Wang W,	Tissue & cell	2026	0
Ferroptosis and microglial polarization in retinal vein occlusion: pathological [PMID:41924362]	Xu J, Sun M, Wang C, Ju P, Guan XD, Xie	International journal of ophth	2026	0
Melatonin Alleviates Erastin-Induced Cell Death by Inhibiting Ferroptosis and Am [PMID:40442550]	Wongjaikam S, Siengdee P, Somnus A, Govi	Neurotoxicity research	2025	0
Acyl-CoA synthetase long-chain family member 4-A novel prognostic marker in cuta [PMID:41918944]	Paria S, Lapides R, Saravi B, Rajagopal	Frontiers in medicine	2025	0
Microglial exosome TREM2 ameliorates ferroptosis and neuroinflammation in alzhei [PMID:40640358]	Zhu L, Zhou T, Wu L, Zhu X, Chen L, Zhan	Scientific reports	2025	0
Microbiota-derived lysophosphatidylcholine alleviates Alzheimer's disease pathol [PMID:39510074]	["Zha Xu", "Liu Xicheng", "Wei Mengping"	Cell metabolism	2025	0
Upregulation of MAM by C99 disrupts ACSL4 activity and phospholipid homeostasis [PMID:41394684]	Montesinos J, Yun TD, Salomón-Cruz ID, A	bioRxiv : the preprint server	2025	0
Danggui Shaoyao San ameliorates Alzheimer's disease by regulating lipid metaboli [PMID:40271063]	Gong K, Zhou S, Xiao L, Xu M, Zhou Y, Lu	Frontiers in pharmacology	2025	0
Single-cell spatial transcriptomics reveals distinct patterns of dysregulation i [PMID:39103533]	Johnston KG, Berackey BT, Tran KM, Gelbe	Molecular psychiatry	2025	0
Deferiprone in Alzheimer Disease: A Randomized Clinical Trial. [PMID:39495531]	Ayton S, Barton D, Brew B, Brodtmann A,	JAMA neurology	2025	0

Debates (4)

Multi-agent debates referencing this entity

Related Research

Hypotheses and analyses mentioning ACSL4 in their description or question text

No additional research found

ACSL4

Understanding Entity Pages

Summary

Wiki Pages (3)

ACSL4 Gene - Acyl-CoA Synthetase Long Chain Family Member 4

ACSL4 Inhibition for Ferroptosis Prevention in Neurodegeneration

ACSL4 Protein

Pathway Diagram

Outgoing (538)

Incoming (209)

Targeting Hypotheses (4)

Mentioning Analyses (4)

Is ferroptosis the primary driver of motor neuron death in ALS or an epiphenomen

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)

Experiments (4)

Related Papers (20)

Debates (4)

The debate highlighted compelling correlative evidence for ferroptosis markers i

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

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