ALOX15
protein-codingarachidonate 15-lipoxygenase, the group of Arachidonate lipoxygenases
Gene summary
This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0000144
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ALOX15 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001140.5. 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 | 2 | 4 | 6 | |||
| missense | 91 | 8 | 4 | 103 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 93 | 10 | 8 | 111 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001131.3 | 14 | MANE Select | |
| Ensembl | ENSP00000293761.3 | 14 | MANE Select | |
| Ensembl | ENSP00000458832.1 | 14 | Standard | |
| Ensembl | ENSP00000458832.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Serotonergic synapse - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- Arachidonic acid metabolism - Homo sapiens (human)
- Linoleic acid metabolism - Homo sapiens (human)
- Ferroptosis - Homo sapiens (human)
Biological Process
- ossification
- negative regulation of adaptive immune response
- phosphatidylethanolamine biosynthetic process
- leukotriene metabolic process
- inflammatory response
Molecular Function
- arachidonate 12-lipoxygenase activity
- iron ion binding
- protein binding
- phosphatidylinositol-4,5-bisphosphate binding
- hepoxilin-epoxide hydrolase activity
Cellular Component
- lipid droplet
- cytosol
- plasma membrane
- membrane
- extrinsic component of cytoplasmic side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000570836
- Coding exons
- 14
- Length
- 11393
- Individuals with no LoFs
- 125472
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 275
- Defined
- 125748
- p
- 0.00110
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0277 | 378 | 380 | 0.996 | 0.0000213 | 4264 |
| Missense (PolyPhen) | 131 | 141.92 | 0.92307 | 1752 | ||
| Synonymous | -1.49 | 186 | 162 | 1.15 | 0.00000952 | 1361 |
| Loss of Function | -0.0496 | 35 | 34.7 | 1.01 | 0.00000178 | 364 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0025 | 0.0025 | notable |
| Latino/Admixed American | 0.0024 | 0.0023 | notable |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00076 | 0.00076 | rare |
| South Asian | 0.0016 | 0.0015 | notable |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Converts arachidonic acid into 12- hydroperoxyeicosatetraenoic acid/12-HPETE and 15- hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)- hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3. Probably plays an important role in the immune and inflammatory responses. Through the oxygenation of membrane-bound phosphatidylethanolamine in macrophages may favor clearance of apoptotic cells during inflammation by resident macrophages and prevent an autoimmune response associated with the clearance of apoptotic cells by inflammatory monocytes. In parallel, may regulate actin polymerization which is crucial for several biological processes, including macrophage function. May also regulate macrophage function through regulation of the peroxisome proliferator activated receptor signaling pathway. Finally, it is also involved in the cellular response to IL13/interleukin-13. In addition to its role in the immune and inflammatory responses, may play a role in epithelial wound healing in the cornea maybe through production of lipoxin A4. May also play a role in endoplasmic reticulum stress response and the regulation of bone mass. {ECO:0000269|PubMed:17052953, ECO:0000269|PubMed:21831839}.;
- Disease
- DISEASE: Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry. Met at position 560 may confer interindividual susceptibility to coronary artery disease (CAD) (PubMed:17959182). {ECO:0000269|PubMed:17959182}.;
Recessive Scores
- pRec
- 0.245
Intolerance Scores
- LoFtool
- 0.935
- RVIS EVS
- -0.13
- RVIS percentile EVS
- 44.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.809
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |