ALOXE3

Chr 17AR

arachidonate epidermal lipoxygenase 3

Also known as: ARCI3, E-LOX, LI5, eLOX-3, eLOX3

NCBI Gene: 59344ENSG00000179148UniProt: Q9BYJ1

This gene is a member of the lipoxygenase family, which are catabolized by arachidonic acid-derived compounds. The encoded enzyme is a hydroperoxide isomerase that synthesizes a unique type of epoxy alcohol (8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid) from 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). This epoxy alcohol can activate the the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha), which is implicated in epidermal differentiation. Loss of function of the enzyme encoded by this gene results in ichthyosis, implicating the function of this gene in the differentiation of human skin. This gene is part of a cluster of lipoxygenase genes on 17p13.1. Mutations in this gene result in nonbullous congenital ichthyosiform erythroderma (NCIE). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Ichthyosis, congenital, autosomal recessive 3MIM #606545
AR
397
ClinVar variants
90
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ALOXE3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
90 Pathogenic / Likely Pathogenic· 177 VUS of 397 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.05LOEUF
pLI 0.000
Z-score 1.26
OE 0.80 (0.61–1.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.15Z-score
OE missense 0.98 (0.91–1.06)
471 obs / 480.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.80 (0.61–1.05)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 35 / 44.0Missense obs/exp: 471 / 480.2Syn Z: 0.41

ClinVar Variant Classifications

397 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic21
VUS177
Likely Benign53
Benign51
Conflicting26
69
Pathogenic
21
Likely Pathogenic
177
VUS
53
Likely Benign
51
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
12
41
1
69
Likely Pathogenic
10
4
7
0
21
VUS
0
133
38
6
177
Likely Benign
0
7
27
19
53
Benign
0
6
40
5
51
Conflicting
—26
Total2516215331397

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ALOXE3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ALOXE3-related congenital ichthyosis

definitive
ARLoss Of FunctionAbsent Gene Product
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ichthyosis, congenital, autosomal recessive 3

MIM #606545

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ALOXE3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis.
He H et al.·J Allergy Clin Immunol
2021
Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients.
Hotz A et al.·Genes (Basel)
2021Meta-analysis
ALOXE3 expression predicts poor prognosis and modulates immune infiltration in colon adenocarcinoma.
Zhao L et al.·World J Surg Oncol
2025
RasGRP4 Exacerbates Diabetic Kidney Fibrosis via Aloxe3-Mediated Oxidative Stress and Scar-Associated Macrophage Activation.
Zhang B et al.·FASEB J
2025
Autosomal recessive congenital ichthyosis.
Rodríguez-Pazos L et al.·Actas Dermosifiliogr
2013Review
Genotypic and clinical spectrum of self-improving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients.
Vahlquist A et al.·J Invest Dermatol
2010Cohort
Novel mutations in the genes TGM1 and ALOXE3 underlying autosomal recessive congenital ichthyosis.
Ullah R et al.·Int J Dermatol
2016
The ALOXE3 gene variants from patients with Dravet syndrome decrease gene expression and enzyme activity.
Gao MM et al.·Brain Res Bull
2021Cohort
Computational recognition of regulator genes and signature for ferroptosis with implications on immunological properties and clinical management of atopic dermatitis.
Xu L et al.·Front Immunol
2024
Growth State-Dependent Expression of Arachidonate Lipoxygenases in the Human Endothelial Cell Line EA.hy926.
Sabbir MG et al.·Cells
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools