ALOX12

Chr 17

arachidonate 12-lipoxygenase, 12S type

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

NCBI Gene: 239 ENSG00000108839 UniProt: P18054 OMIM: 152391

This gene encodes 12-lipoxygenase, an enzyme that converts polyunsaturated fatty acids like arachidonic acid into bioactive lipid mediators including eicosanoids and lipoxins that regulate platelet function and inflammatory responses. The gene shows very low constraint against loss-of-function variants (LOEUF 1.039), and while genetic variants have been associated with toxoplasmosis susceptibility, no clear Mendelian neurological disorders have been established. Clinical significance in pediatric neurology remains unclear based on current genetic evidence.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.04

Clinical Summary— ALOX12

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

72 VUS of 124 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

1.27Z-score

OE missense 0.82 (0.74–0.90)

308 obs / 377.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.56–1.04)

0≤0.351.4

Missense OE?0.82 (0.74–0.90)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 28 / 36.9Missense obs/exp: 308 / 377.7Syn Z: 1.57

This gene — mechanism propensity

0.5575th %ile

GOF

0.6932th %ile

LOF

0.3067th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

124 submitted variants in ClinVar

ClinVar

Classification Summary

VUS72

Likely Benign10

Benign33

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	72	0	0	72
Likely Benign	7	1	2	10
Benign	4	24	5	33
Total	83	25	7	115

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap ALOX12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →