ALOX12

Chr 17

arachidonate 12-lipoxygenase, 12S type

Also known as: 12-LOX, 12S-LOX, LOG12

NCBI Gene: 239ENSG00000108839UniProt: P18054

This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on different polyunsaturated fatty acid substrates to generate bioactive lipid mediators including eicosanoids and lipoxins. The encoded enzyme and its reaction products have been shown to regulate platelet function. Elevated expression of this gene has been observed in pancreatic islets derived from human diabetes patients. Allelic variants in this gene may be associated with susceptibility to toxoplasmosis. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

Primary Disease Associations & Inheritance

UniProtEsophageal cancer
UniProtColorectal cancer
141
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ALOX12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 79 VUS of 141 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.
1.04LOEUF
pLI 0.000
Z-score 1.36
OE 0.76 (0.56–1.04)
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.
1.27Z-score
OE missense 0.82 (0.74–0.90)
308 obs / 377.7 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.0.76 (0.56–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.74–0.90)
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.0.84
0≤1.21.6
LoF obs/exp: 28 / 36.9Missense obs/exp: 308 / 377.7Syn Z: 1.57

ClinVar Variant Classifications

141 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS79
Likely Benign10
Benign33
18
Pathogenic
1
Likely Pathogenic
79
VUS
10
Likely Benign
33
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
72
7
0
79
Likely Benign
0
7
1
2
10
Benign
0
4
24
5
33
Total083517141

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

View in ClinVar →

Protein Context — Lollipop Plot

ALOX12 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Landscape of pathogenic mutations in premature ovarian insufficiency.
Ke H et al.·Nat Med
2023
An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury.
Zhang XJ et al.·Nat Med
2018
Inhibition of PGK1 ameliorates acute kidney injury through inactivating the PKM2/ALOX12/ferroptosis pathway in a study with male mice.
Zhu XX et al.·Nat Commun
2025
Palmitic acid inhibits macrophage-mediated chemotherapy resistance in multiple myeloma via ALOX12 signaling.
Dong H et al.·Int Immunopharmacol
2024
Elevated ALOX12 in renal tissue predicts progression in diabetic kidney disease.
Wang M et al.·Ren Fail
2024
Whole-gene CRISPR/cas9 library screen revealed targeting STAT6 increased the sensitivity of liver cancer to celecoxib via inhibiting arachidonic acid shunting.
Hu C et al.·Cell Commun Signal
2025
ALOX12: A Novel Insight in Bevacizumab Response, Immunotherapy Effect, and Prognosis of Colorectal Cancer.
Weng S et al.·Front Immunol
2022
Identification of N6-methyladenosine-associated ferroptosis biomarkers in cervical cancer.
Liu J et al.·Hereditas
2025
Alox12/15 Deficiency Exacerbates, While Lipoxin A(4) Ameliorates Hepatic Inflammation in Murine Alcoholic Hepatitis.
Queck A et al.·Front Immunol
2020
Diesel exhaust induces gut microbiome dysbiosis and reduced fecal acetate: Role of acetate supplementation.
Gupta R et al.·Ecotoxicol Environ Saf
2025
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