ALOX15

Chr 17

arachidonate 15-lipoxygenase

Also known as: 12-LOX, 15-LOX, 15-LOX-1, LOG15

NCBI Gene: 246 ENSG00000161905 UniProt: P16050 OMIM: 152392

The protein is a lipoxygenase enzyme that catalyzes the peroxidation of polyunsaturated fatty acids to generate bioactive lipid mediators including eicosanoids, hepoxilins, and specialized pro-resolving mediators that regulate inflammation and immunity. Mutations in this gene cause ichthyosis with hypotrichosis, which follows autosomal recessive inheritance and primarily affects the skin and hair follicles. The gene shows no significant constraint against loss-of-function variants (pLI near zero, LOEUF 1.338).

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.34

Clinical Summary— ALOX15

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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

92 VUS of 115 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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?

1.34LOEUF

pLI 0.000

Z-score -0.05

OE 1.01 (0.77–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.03Z-score

OE missense 1.00 (0.92–1.08)

378 obs / 379.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.01 (0.77–1.34)

0≤0.351.4

Missense OE?1.00 (0.92–1.08)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 35 / 34.7Missense obs/exp: 378 / 379.5Syn Z: -1.49

This gene — mechanism propensity

0.5378th %ile

GOF

0.7028th %ile

LOF

0.3260th %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

115 submitted variants in ClinVar

ClinVar

Classification Summary

VUS92

Likely Benign10

Benign9

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	91	0	0	92
Likely Benign	0	8	0	2	10
Benign	0	4	1	4	9
Total	1	103	1	6	111

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap ALOX15 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →