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GeneE
10 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.
ALOXE3
arachidonate epidermal lipoxygenase 3
Chromosome 17 Β· 17p13.1
NCBI Gene: 59344Ensembl: ENSG00000179148.11HGNC: HGNC:13743UniProt: A0AAQ5BHH1
42PubMed Papers
21Diseases
0Drugs
65Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygenprotein bindingintramolecular hydroxytransferase activityhydroperoxy icosatetraenoate isomerase activityautosomal recessive congenital ichthyosiscongenital non-bullous ichthyosiform erythrodermalamellar ichthyosisself-healing collodion baby
✦AI Summary

ALOXE3 encodes an atypical lipoxygenase with prominent hydroperoxide isomerase activity that catalyzes conversion of arachidonic and linoleic acid-derived hydroperoxides into hepoxilin-type epoxyalcohols and ketones 12. In skin, ALOXE3 acts downstream of ALOX12B to modify esterified omega-hydroxyacyl-sphingosine ceramides, producing epoxy-ketone derivatives essential for corneocyte lipid envelope synthesis and establishing the skin barrier to water loss 3. Loss-of-function mutations in ALOXE3 represent the second most common cause of autosomal recessive congenital ichthyosis (ARCI), with 27 pathogenic variants identified to date 4. ALOXE3 expression is significantly downregulated in both atopic dermatitis and psoriasis lesions, contributing to barrier dysfunction 5. Beyond dermatology, ALOXE3 variants in Dravet syndrome patients decrease gene expression and enzyme activity, suggesting involvement in arachidonic acid-pathway-mediated epileptogenesis 6. In cancer biology, ALOXE3 expression predicts poor prognosis in colon adenocarcinoma through ERK1/2 signaling pathway activation and modulation of tumor immune infiltration 7. Additionally, ALOXE3 contributes to diabetic kidney fibrosis via oxidative stress and scar-associated macrophage activation 8.

Sources cited
1
ALOXE3 displays prominent hydroperoxide isomerase activity and reduced lipoxygenase activity
PMID: 12881489
2
ALOXE3 catalyzes isomerization of hydroperoxides into hepoxilin-type epoxyalcohols
PMID: 17045234
3
ALOXE3 modifies EOS ceramides in skin and plays crucial role in corneocyte lipid envelope synthesis and skin barrier function
PMID: 21558561
4
ALOXE3 mutations are the second most common cause of ARCI with 27 pathogenic variants reported
PMID: 33435499
5
ALOXE3 expression is significantly downregulated in both atopic dermatitis and psoriasis lesions
PMID: 32709423
6
ALOXE3 variants in Dravet syndrome patients decrease gene expression and enzyme activity, affecting arachidonic acid metabolism
PMID: 33581311
7
ALOXE3 expression predicts poor prognosis in colon adenocarcinoma through ERK1/2 signaling pathway activation
PMID: 40696372
8
ALOXE3 contributes to diabetic kidney fibrosis via oxidative stress and scar-associated macrophage activation
PMID: 40662951
Disease Associationsβ“˜21
autosomal recessive congenital ichthyosisOpen Targets
0.71Strong
congenital non-bullous ichthyosiform erythrodermaOpen Targets
0.64Moderate
lamellar ichthyosisOpen Targets
0.60Moderate
self-healing collodion babyOpen Targets
0.59Moderate
ichthyosisOpen Targets
0.51Moderate
congenital reticular ichthyosiform erythrodermaOpen Targets
0.40Weak
inherited ichthyosisOpen Targets
0.37Weak
Abnormal form of the vertebral bodiesOpen Targets
0.34Weak
Delayed ability to standOpen Targets
0.34Weak
Delayed ability to walkOpen Targets
0.34Weak
Failure to thrive in infancyOpen Targets
0.34Weak
hypophosphatemiaOpen Targets
0.34Weak
Intellectual disabilityOpen Targets
0.34Weak
Lumbar kyphoscoliosisOpen Targets
0.34Weak
Mild global developmental delayOpen Targets
0.34Weak
Progressive congenital scoliosisOpen Targets
0.34Weak
scoliosisOpen Targets
0.34Weak
Short statureOpen Targets
0.34Weak
Thoracic scoliosisOpen Targets
0.34Weak
Vertebral fusionOpen Targets
0.34Weak
Ichthyosis, congenital, autosomal recessive 3UniProt
Pathogenic Variants65
NM_021628.3(ALOXE3):c.1889C>T (p.Pro630Leu)Pathogenic
Autosomal recessive congenital ichthyosis 3|not provided|Autosomal recessive congenital ichthyosis|Lamellar ichthyosis|ALOXE3-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 630
NM_021628.3(ALOXE3):c.700C>T (p.Arg234Ter)Pathogenic
Autosomal recessive congenital ichthyosis 3|not provided|ALOXE3-related disorder|Autosomal recessive congenital ichthyosis 2;Autosomal recessive congenital ichthyosis 3
β˜…β˜…β˜†β˜†2026β†’ Residue 234
NM_021628.3(ALOXE3):c.631C>T (p.Arg211Ter)Pathogenic
not provided|Autosomal recessive congenital ichthyosis 3|ALOXE3-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 211
NM_021628.3(ALOXE3):c.2065C>T (p.Arg689Trp)Pathogenic
Autosomal recessive congenital ichthyosis 2|Lamellar ichthyosis|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 689
NM_021628.3(ALOXE3):c.1786-2A>GLikely pathogenic
not provided|Autosomal recessive congenital ichthyosis 3
β˜…β˜…β˜†β˜†2025
NM_021628.3(ALOXE3):c.1630C>T (p.Gln544Ter)Pathogenic
not provided|Lamellar ichthyosis|Congenital nonbullous ichthyosiform erythroderma
β˜…β˜…β˜†β˜†2025β†’ Residue 544
NM_021628.3(ALOXE3):c.680+1G>APathogenic
Autosomal recessive congenital ichthyosis 3|Lamellar ichthyosis|Trichohepatoenteric syndrome 2
β˜…β˜…β˜†β˜†2025
NM_021628.3(ALOXE3):c.1208A>G (p.His403Arg)Likely pathogenic
Autosomal recessive congenital ichthyosis 2|Autosomal recessive congenital ichthyosis 3|Lamellar ichthyosis
β˜…β˜…β˜†β˜†2024β†’ Residue 403
NM_021628.3(ALOXE3):c.1685-2A>GLikely pathogenic
Autosomal recessive congenital ichthyosis 3|Autosomal recessive congenital ichthyosis 3;Autosomal recessive congenital ichthyosis 2
β˜…β˜…β˜†β˜†2023
NM_021628.3(ALOXE3):c.434G>A (p.Arg145His)Pathogenic
Autosomal recessive congenital ichthyosis 3|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 145
NM_021628.3(ALOXE3):c.834C>A (p.Tyr278Ter)Pathogenic
Autosomal recessive congenital ichthyosis 2|Autosomal recessive congenital ichthyosis 3|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 278
NM_021628.3(ALOXE3):c.1981G>T (p.Glu661Ter)Likely pathogenic
Lamellar ichthyosis
β˜…β˜†β˜†β˜†2024β†’ Residue 661
NM_021628.3(ALOXE3):c.265_266del (p.Val89fs)Likely pathogenic
Autosomal recessive congenital ichthyosis 3
β˜…β˜†β˜†β˜†2024β†’ Residue 89
NM_021628.3(ALOXE3):c.367C>T (p.Gln123Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 123
NM_021628.3(ALOXE3):c.1645G>T (p.Glu549Ter)Likely pathogenic
Autosomal recessive congenital ichthyosis 3
β˜…β˜†β˜†β˜†2024β†’ Residue 549
NM_021628.3(ALOXE3):c.1166dup (p.Leu390fs)Likely pathogenic
Autosomal recessive congenital ichthyosis 3
β˜…β˜†β˜†β˜†2024β†’ Residue 390
NM_021628.3(ALOXE3):c.952dup (p.Leu318fs)Likely pathogenic
Autosomal recessive congenital ichthyosis 3
β˜…β˜†β˜†β˜†2024β†’ Residue 318
NM_021628.3(ALOXE3):c.1802G>A (p.Trp601Ter)Likely pathogenic
Autosomal recessive congenital ichthyosis 3
β˜…β˜†β˜†β˜†2024β†’ Residue 601
NM_021628.3(ALOXE3):c.784+1G>APathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_021628.3(ALOXE3):c.1843C>T (p.Gln615Ter)Likely pathogenic
Autosomal recessive congenital ichthyosis 3
β˜…β˜†β˜†β˜†2024β†’ Residue 615
View on ClinVar β†—
Related Genes
NIPAL4Protein interaction96%ABHD5Protein interaction92%CYP4F22Protein interaction92%TGM1Protein interaction90%ABCA12Protein interaction90%LOXProtein interaction81%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
88%
Ovary
12%
Lung
9%
Liver
6%
Heart
0%
Gene Interaction Network
Click a node to explore
ALOXE3NIPAL4ABHD5CYP4F22TGM1ABCA12LOX
PROTEIN STRUCTURE
Preparing viewer…
PDB6VB2 Β· 1.41 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.04LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.86 [0.71–1.04]
RankingsWhere ALOXE3 stands among ~20K protein-coding genes
  • #9,830of 20,598
    Most Researched42
  • #1,112of 5,498
    Most Pathogenic Variants65 Β· top quartile
  • #10,296of 17,882
    Most Constrained (LOEUF)1.04
Genes detectedALOXE3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
SBFI26 induces triple-negative breast cancer cells ferroptosis via lipid peroxidation.
PMID: 38516826
J Cell Mol Med Β· 2024
1.00
2
Targeting inhibition of prognosis-related lipid metabolism genes including CYP19A1 enhances immunotherapeutic response in colon cancer.
PMID: 37055842
J Exp Clin Cancer Res Β· 2023
0.90
3
Meta-Analysis of Mutations in
PMID: 33435499
Genes (Basel) Β· 2021
0.80
4
Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis.
PMID: 32709423
J Allergy Clin Immunol Β· 2021
0.70
5
The ALOXE3 gene variants from patients with Dravet syndrome decrease gene expression and enzyme activity.
PMID: 33581311
Brain Res Bull Β· 2021
0.60