ALOX15B

Chr 17

arachidonate 15-lipoxygenase type B

Also known as: 15-LOX-2

NCBI Gene: 247 ENSG00000179593 UniProt: O15296

The protein is a lipoxygenase enzyme that catalyzes the peroxidation of polyunsaturated fatty acids like arachidonic acid to produce bioactive lipid mediators involved in inflammation resolution and immune regulation. Mutations cause autosomal recessive ichthyosis with onset in infancy, characterized by severe skin abnormalities including thick scaling and erythroderma. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.18

Clinical Summary— ALOX15B

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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

113 VUS of 136 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.000

Z-score 0.69

OE 0.87 (0.65–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.27Z-score

OE missense 0.96 (0.88–1.05)

383 obs / 398.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.65–1.18)

0≤0.351.4

Missense OE?0.96 (0.88–1.05)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 30 / 34.4Missense obs/exp: 383 / 398.3Syn Z: 1.42

This gene — mechanism propensity

0.5574th %ile

GOF

0.6931th %ile

LOF

0.3261th %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

136 submitted variants in ClinVar

ClinVar

Classification Summary

VUS113

Likely Benign10

Benign2

113

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	113	0	0	113
Likely Benign	8	0	2	10
Benign	1	1	0	2
Total	122	1	2	125

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap ALOX15B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →