ALOX5AP

Chr 13

arachidonate 5-lipoxygenase activating protein

Also known as: FLAP

NCBI Gene: 241 ENSG00000132965 UniProt: P20292

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. Leukotrienes are arachidonic acid metabolites which have been implicated in various types of inflammatory responses, including asthma, arthritis and psoriasis. This protein localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIschemic stroke

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ALOX5AP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

256 rare PASS variants

Rare truncating (LoF)

1 in 910

38 rare PASS variants

Rare synonymous (reference)

1 in 190

111 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ALOX5AP; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 310	1 in 1,600
South Asian	~43k	1 in 240	1 in 5,700
Remaining (unassigned)	~30k	1 in 360	1 in 750
European (Finnish)	~27k	1 in 650	≈ 1 in 5,500
Admixed American	~22k	1 in 290	1 in 1,400
African / African American	~21k	1 in 290	1 in 2,600
East Asian	~20k	1 in 320	1 in 520
Ashkenazi Jewish	~13k	≈ 1 in 13,000	1 in 1,200
Middle Eastern	~2,884	1 in 240	1 in 550

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓