ALOX5AP

protein-coding

arachidonate 5-lipoxygenase activating protein

Gene summary

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]

MANE transcript

NM_001629.4

Inheritance

—

ClinVar variants

U:17B:4

Top phenotype

ALOX5AP-related disorder

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr13:30,713,478-30,764,426

External References & Databases

Ensembl (ENSG00000132965)

Transcript & Mutation Effects

hg38 • Region Span ~50.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ALOX5AP variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 16

not providedTotal: 4

ALOX5AP-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001629.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	1 clinvar	4
missense			17 clinvar			17
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	17	3	1	21

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001629.4	RefSeq	NP_001620.2	5	MANE Select
ENST00000380490.5	Ensembl	ENSP00000369858.3	5	MANE Select
NM_001204406.2	RefSeq	NP_001191335.1	6	Standard
ENST00000617770.4	Ensembl	ENSP00000479870.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
alox5ap	Danio rerio	Structure: intersegmental vessel Quality: decreased functionality abnormal

Gene / Model

Organism

Observed Phenotype

alox5ap

Danio rerio

Structure: intersegmental vessel

Quality: decreased functionality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fc epsilon RI signaling pathway - Homo sapiens (human)
Leukotriene modifiers pathway, Pharmacodynamics
Selenium Micronutrient Network
Eicosanoid Synthesis
Glucocorticoid Receptor Pathway

Biological Process

leukotriene biosynthetic process
positive regulation of catalytic activity
protein homotrimerization
cellular response to calcium ion
cellular oxidant detoxification

Molecular Function

glutathione transferase activity
leukotriene-C4 synthase activity
glutathione peroxidase activity
protein binding
enzyme activator activity

Cellular Component

nuclear envelope
endoplasmic reticulum
endoplasmic reticulum membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380490
Coding exons: 5
Length: 28912
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125747
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	68	96.9	0.702	0.00000563	1056
Missense (PolyPhen)		24	40.29	0.59568		416
Synonymous	0.907	33	40.3	0.818	0.00000272	317
Loss of Function	1.65	3	8.05	0.373	3.43e-7	92

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for leukotriene biosynthesis by ALOX5 (5- lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes. {ECO:0000269|PubMed:2300173, ECO:0000269|PubMed:8440384}.;
Disease: DISEASE: Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=Genetic variations in ALOX5AP may be associated with susceptibility to myocardial infarction. Involvement in myocardial infarction is however unclear: according to some authors (PubMed:14770184), a 4-SNP haplotype in ALOX5AP confers risk of myocardial infarction, while according to other (PubMed:17304054) ALOX5AP is not implicated in this condition. {ECO:0000269|PubMed:14770184, ECO:0000269|PubMed:17304054}.;

Recessive Scores

pRec: 0.291

Intolerance Scores

RVIS EVS: -0.23
RVIS percentile EVS: 36.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.584

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium