ALOX5
protein-codingarachidonate 5-lipoxygenase, the group of Arachidonate lipoxygenases
Gene summary
This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~71.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: Variants may have pharmacogenomic importance
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ALOX5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000698.5. 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 | 7 | 10 | 1 | 18 | ||
| missense | 84 | 6 | 90 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 98 | 16 | 1 | 115 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000689.1 | 14 | MANE Select | |
| Ensembl | ENSP00000363512.2 | 14 | MANE Select | |
| RefSeq | NP_001243082.1 | 14 | Standard | |
| RefSeq | NP_001243083.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fc epsilon RI signaling pathway - Homo sapiens (human)
- Serotonergic synapse - Homo sapiens (human)
- Arachidonic acid metabolism - Homo sapiens (human)
- Toxoplasmosis - Homo sapiens (human)
- Ovarian steroidogenesis - Homo sapiens (human)
Biological Process
- leukotriene production involved in inflammatory response
- leukotriene metabolic process
- cytokine-mediated signaling pathway
- leukotriene biosynthetic process
- lipoxygenase pathway
Molecular Function
- arachidonate 5-lipoxygenase activity
- iron ion binding
- protein binding
Cellular Component
- extracellular region
- extracellular space
- nuclear envelope
- nuclear envelope lumen
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374391
- Coding exons
- 14
- Length
- 71901
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125748
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.09 | 363 | 427 | 0.851 | 0.0000278 | 4413 |
| Missense (PolyPhen) | 130 | 177.85 | 0.73096 | 1931 | ||
| Synonymous | -0.230 | 184 | 180 | 1.02 | 0.0000129 | 1246 |
| Loss of Function | 3.38 | 17 | 40.1 | 0.424 | 0.00000232 | 392 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes. {ECO:0000269|PubMed:21233389}.;
Recessive Scores
- pRec
- 0.388
Intolerance Scores
- LoFtool
- 0.255
- RVIS EVS
- -0.95
- RVIS percentile EVS
- 9.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.970
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |