ALOX12B

Chr 17AR

arachidonate 12-lipoxygenase, 12R type

Also known as: 12R-LOX, ARCI2

The protein catalyzes the incorporation of oxygen into polyunsaturated fatty acids and plays a crucial role in skin barrier formation by acting on ceramides to synthesize the corneocyte lipid envelope. Mutations cause autosomal recessive congenital ichthyosiform erythroderma, a severe skin disorder present from birth characterized by scaling and redness. The gene shows low constraint against loss-of-function variants (pLI 0.0008, LOEUF 0.55), consistent with the recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.551 OMIM phenotype
Clinical SummaryALOX12B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
171 unique Pathogenic / Likely Pathogenic· 175 VUS of 473 total submissions
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GeneReview available — ALOX12B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.001
Z-score 3.63
OE 0.34 (0.220.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.40Z-score
OE missense 0.80 (0.730.88)
326 obs / 405.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.220.55)
00.351.4
Missense OE0.80 (0.730.88)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 12 / 35.2Missense obs/exp: 326 / 405.6Syn Z: 0.60
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveALOX12B-related congenital ichthyosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6260th %ile
GOF
0.7028th %ile
LOF
0.2679th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

473 submitted variants in ClinVar

Classification Summary

Pathogenic126
Likely Pathogenic45
VUS175
Likely Benign51
Benign38
Conflicting31
126
Pathogenic
45
Likely Pathogenic
175
VUS
51
Likely Benign
38
Benign
31
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
53
49
24
0
126
Likely Pathogenic
17
26
2
0
45
VUS
0
137
30
8
175
Likely Benign
0
4
22
25
51
Benign
0
1
33
4
38
Conflicting
31
Total7021711137466

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

View in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →