ALOX12B

Chr 17AR

arachidonate 12-lipoxygenase, 12R type

Also known as: 12R-LOX, ARCI2

NCBI Gene: 242ENSG00000179477UniProt: O75342

This gene encodes an enzyme involved in the conversion of arachidonic acid to 12R-hydroxyeicosatetraenoic acid. Mutations in this gene are associated with nonbullous congenital ichthyosiform erythroderma. [provided by RefSeq, Sep 2015]

Primary Disease Associations & Inheritance

Ichthyosis, congenital, autosomal recessive 2MIM #242100
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ALOX12B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.55LOEUF
pLI 0.001
Z-score 3.63
OE 0.34 (0.22–0.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.40Z-score
OE missense 0.80 (0.73–0.88)
326 obs / 405.6 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.0.34 (0.22–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.73–0.88)
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.0.94
0≤1.21.6
LoF obs/exp: 12 / 35.2Missense obs/exp: 326 / 405.6Syn Z: 0.60

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ALOX12B · protein map & ClinVar variants

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

Gene2Phenotype Curations

ALOX12B-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 2

MIM #242100

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ALOX12B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients.
Hotz A et al.·Genes (Basel)
2021Meta-analysis
Beyond the skin: immunological profiles and infectious complications in ALOX12B-associated autosomal recessive congenital ichthyosis.
Sefer AP et al.·Front Immunol
2025
Autosomal recessive congenital ichthyosis.
Rodríguez-Pazos L et al.·Actas Dermosifiliogr
2013Review
Whole exome sequencing identifies novel pathogenic variants in TGM1 and ALOX12B in patients with hereditary ichthyosis.
Chegini M et al.·Arch Dermatol Res
2023Cohort
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
Molecular insights into genodermatoses: Genetic findings from 43 patients.
Sama AD et al.·Arch Dermatol Res
2025Cohort
Survival-related indicators ALOX12B and SPRR1A are associated with DNA damage repair and tumor microenvironment status in HPV 16-negative head and neck squamous cell carcinoma patients.
Li J et al.·BMC Cancer
2022Cohort
[Clinical and genetic analysis of a patient with autosomal recessive congenital ichthyosis due to compound heterozygous variants of ALOX12B gene].
Li D et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2022
Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.
Simpson JK et al.·Br J Dermatol
2020Cohort
Novel mutations in ALOX12B in patients with autosomal recessive congenital ichthyosis and evidence for genetic heterogeneity on chromosome 17p13.
Lesueur F et al.·J Invest Dermatol
2007Cohort
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