ALOX5AP

Chr 13Multi

arachidonate 5-lipoxygenase activating protein

Also known as: FLAP

The protein anchors 5-lipoxygenase to the membrane and is required for leukotriene biosynthesis from arachidonic acid, playing a key role in inflammatory responses. Mutations are associated with stroke susceptibility through multifactorial inheritance. The gene shows tolerance to loss-of-function variants, consistent with its role as a susceptibility factor rather than a cause of Mendelian disease.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismMultiLOEUF 0.961 OMIM phenotype
Clinical SummaryALOX5AP
Population Constraint (gnomAD)
Low constraint (pLI 0.07) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.071
Z-score 1.65
OE 0.37 (0.170.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.04Z-score
OE missense 0.70 (0.580.86)
68 obs / 96.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.170.96)
00.351.4
Missense OE0.70 (0.580.86)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 3 / 8.0Missense obs/exp: 68 / 96.9Syn Z: 0.91
DN
0.80top 25%
GOF
0.6833th %ile
LOF
0.1797th %ile

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

DNprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ALOX5AP · 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
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