HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ACSL4
acyl-CoA synthetase long chain family member 4
Chromosome X Β· Xq23
NCBI Gene: 2182Ensembl: ENSG00000068366.22HGNC: HGNC:3571UniProt: O60488
196PubMed Papers
22Diseases
0Drugs
14Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
long-chain fatty acid-CoA ligase activityvery long-chain fatty acid-CoA ligase activityarachidonate-CoA ligase activitylong-chain fatty acid metabolic processX-linked non-syndromic intellectual disabilityneurodegenerative diseaseAlport syndrome - intellectual disability - midface hypoplasia - elliptocytosisAlport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
✦AI Summary

ACSL4 is a long-chain fatty acyl-CoA synthetase that catalyzes conversion of long-chain polyunsaturated fatty acids (PUFAs), particularly arachidonate and eicosapentaenoate, to their active acyl-CoA forms 1. This activation is critical for both lipid biosynthesis and beta-oxidation 12. ACSL4's primary pathophysiological role centers on ferroptosis regulation: it generates lipid-peroxidation substrates by activating PUFAs, particularly arachidonate, thereby promoting ferroptosis execution 34. ACSL4 remodels cellular membrane composition by enriching membranes with polyunsaturated omega-6 fatty acids, determining ferroptosis sensitivity 3. Beyond ferroptosis, ACSL4 modulates glucose-stimulated insulin secretion and prostaglandin E2 secretion 1. Clinically, ACSL4 has emerged as significant in multiple pathologies: it promotes metastatic extravasation in cancer by enhancing membrane fluidity and invasiveness 5, drives ferroptotic cardiomyocyte injury in doxorubicin cardiotoxicity 6, mediates sepsis-associated lung injury through lactate-induced ferroptosis 7, and contributes to ischemic stroke neuronal death 8 and hypertension-associated chrX kidney disease 9. ACSL4 inhibition represents a therapeutic target for ferroptosis-related diseases and cancer progression.

Sources cited
1
ACSL4 catalyzes conversion of long-chain fatty acids to acyl-CoA, preferentially activates arachidonate and eicosapentaenoate, and modulates prostaglandin E2 secretion
PMID: 21242590
2
ACSL4 participates in synthesis of cellular lipids and degradation via beta-oxidation
PMID: 24269233
3
ACSL4 is essential for ferroptosis execution, enriches membranes with polyunsaturated omega-6 fatty acids, and determines ferroptosis sensitivity
PMID: 27842070
4
ACSL4 acts as an activator of ferroptosis by generating lipid-peroxidation substrates
PMID: 35027735
5
ACSL4 promotes metastatic extravasation by enhancing membrane fluidity and cellular invasiveness in cancer metastasis
PMID: 39591965
6
ACSL4 phosphorylation contributes to doxorubicin-induced cardiomyocyte ferroptosis and cardiac dysfunction
PMID: 38984448
7
ACSL4 upregulation promotes ferroptosis in sepsis-associated lung injury through lactate-mediated pathways
PMID: 38852200
8
Thrombin promotes ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion injury
PMID: 35197442
9
STING/ACSL4 axis-dependent ferroptosis promotes hypertension-associated chronic kidney disease
PMID: 37533255
Disease Associationsβ“˜22
X-linked non-syndromic intellectual disabilityOpen Targets
0.74Strong
neurodegenerative diseaseOpen Targets
0.54Moderate
Alport syndrome - intellectual disability - midface hypoplasia - elliptocytosisOpen Targets
0.51Moderate
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndromeOpen Targets
0.51Moderate
non-syndromic X-linked intellectual disabilityOpen Targets
0.48Moderate
Parkinson diseaseOpen Targets
0.38Weak
Alzheimer diseaseOpen Targets
0.38Weak
multiple sclerosisOpen Targets
0.37Weak
lysosomal storage diseaseOpen Targets
0.37Weak
Intellectual disabilityOpen Targets
0.31Weak
neuroinflammatory disorderOpen Targets
0.26Weak
osteoarthritis, kneeOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
medical procedureOpen Targets
0.17Weak
autism spectrum disorderOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
triple-negative breast cancerOpen Targets
0.10Weak
SepsisOpen Targets
0.10Suggestive
AMME complexUniProt
Intellectual developmental disorder, X-linked 63UniProt
Pathogenic Variants14
NM_001318510.2(ACSL4):c.1315+1G>ALikely pathogenic
Intellectual disability, X-linked 63
β˜…β˜†β˜†β˜†2024
NM_001318510.2(ACSL4):c.1001C>T (p.Pro334Leu)Likely pathogenic
Intellectual disability, X-linked 63|not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 334
NM_001318510.2(ACSL4):c.727C>T (p.Arg243Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 243
NM_001318510.2(ACSL4):c.629_630insC (p.Glu210fs)Likely pathogenic
Intellectual disability, X-linked 63
β˜…β˜†β˜†β˜†2023β†’ Residue 210
NM_001318510.2(ACSL4):c.1653_1654insT (p.Lys552Ter)Likely pathogenic
Intellectual disability, X-linked 63
β˜…β˜†β˜†β˜†2022β†’ Residue 552
NM_001318510.2(ACSL4):c.802del (p.Leu268fs)Pathogenic
Intellectual disability, X-linked 63
β˜…β˜†β˜†β˜†2022β†’ Residue 268
NM_001318510.2(ACSL4):c.1072_1073del (p.Leu358fs)Likely pathogenic
Intellectual disability, X-linked 63
β˜…β˜†β˜†β˜†2021β†’ Residue 358
NM_001318510.2(ACSL4):c.1712T>G (p.Val571Gly)Likely pathogenic
Intellectual disability
β˜…β˜†β˜†β˜†2019β†’ Residue 571
NM_001318510.2(ACSL4):c.845_846del (p.His282fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2015β†’ Residue 282
NM_001318510.2(ACSL4):c.1235dup (p.Met413fs)Pathogenic
Intellectual disability, X-linked 63
β˜…β˜†β˜†β˜†β†’ Residue 413
NM_001318510.2(ACSL4):c.257del (p.Asn86fs)Likely pathogenic
Intellectual disability, X-linked 63
β˜†β˜†β˜†β˜†2022β†’ Residue 86
NM_001318510.2(ACSL4):c.473C>A (p.Ser158Tyr)Likely pathogenic
Intellectual disability, X-linked 63
β˜†β˜†β˜†β˜†2019β†’ Residue 158
NM_001318510.2(ACSL4):c.1003-2A>GPathogenic
Intellectual disability, X-linked 63
β˜†β˜†β˜†β˜†2002
NM_001318510.2(ACSL4):c.1585C>A (p.Arg529Ser)Pathogenic
Intellectual disability, X-linked 63
β˜†β˜†β˜†β˜†2002β†’ Residue 529
View on ClinVar β†—
Related Genes
ABCD3Protein interaction98%FASNProtein interaction98%LPLProtein interaction94%MGLLProtein interaction94%COL4A5Protein interaction94%AMMECR1Protein interaction94%
Tissue Expression6 tissues
Heart
100%
Lung
98%
Brain
97%
Ovary
32%
Bone Marrow
25%
Liver
15%
Gene Interaction Network
Click a node to explore
ACSL4ABCD3FASNLPLMGLLCOL4A5AMMECR1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O60488
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.32Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.18 [0.11–0.32]
RankingsWhere ACSL4 stands among ~20K protein-coding genes
  • #2,156of 20,598
    Most Researched196 Β· top quartile
  • #2,499of 5,498
    Most Pathogenic Variants14
  • #1,287of 17,882
    Most Constrained (LOEUF)0.32 Β· top 10%
Genes detectedACSL4
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
ACSL4 and polyunsaturated lipids support metastatic extravasation and colonization.
PMID: 39591965
Cell Β· 2025
1.00
2
Protosappanin A Protects DOX-Induced Myocardial Injury and Cardiac Dysfunction by Targeting ACSL4/FTH1 Axis-Dependent Ferroptosis.
PMID: 38984448
Adv Sci (Weinh) Β· 2024
0.90
3
Histone lactylation-regulated METTL3 promotes ferroptosis via m6A-modification on ACSL4 in sepsis-associated lung injury.
PMID: 38852200
Redox Biol Β· 2024
0.80
4
CD8
PMID: 35216678
Cancer Cell Β· 2022
0.70
5
Uridine Alleviates Sepsis-Induced Acute Lung Injury by Inhibiting Ferroptosis of Macrophage.
PMID: 36982166
Int J Mol Sci Β· 2023
0.68