ALOX5

Chr 10AD

arachidonate 5-lipoxygenase

Also known as: 5-LO, 5-LOX, 5LPG, LOG5

The protein catalyzes the conversion of arachidonic acid to leukotriene A4, the first two steps in leukotriene biosynthesis, and also participates in the synthesis of specialized pro-resolving mediators that have anti-inflammatory effects. Mutations are associated with diminished response to antileukotriene drugs in asthma treatment and susceptibility to atherosclerosis, following an autosomal dominant inheritance pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.636), indicating that complete loss of function is likely deleterious.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

{Asthma, diminished response to antileukotriene treatment in}MIM #600807
AD
{Atherosclerosis, susceptibility to}
1
Active trials
126
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.64
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryALOX5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.000
Z-score 3.38
OE 0.42 (0.290.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.09Z-score
OE missense 0.85 (0.780.93)
363 obs / 426.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.290.64)
00.351.4
Missense OE0.85 (0.780.93)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 17 / 40.1Missense obs/exp: 363 / 426.5Syn Z: -0.23
DN
0.6356th %ile
GOF
0.72top 25%
LOF
0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ALOX5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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