ALOX15

arachidonate 15-lipoxygenase, the group of Arachidonate lipoxygenases

Basic information

Region (hg38): 17:4630919-4642294

Links

ENSG00000161905 ∙ NCBI:246 ∙ OMIM:152392 ∙ HGNC:433 ∙ Uniprot:P16050 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pregnancy loss, recurrent, susceptibility (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALOX15 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALOX15 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	4	6
missense			32	3	3	38
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	33	5	8

Variants in ALOX15

This is a list of pathogenic ClinVar variants found in the ALOX15 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-4631648-G-C			Benign (Mar 05, 2018)
17-4631670-C-T		not specified	Uncertain significance (Jun 09, 2022)
17-4631679-A-G		not specified	Uncertain significance (Jun 01, 2023)
17-4631688-T-C		not specified	Uncertain significance (Dec 06, 2022)
17-4631733-G-C		not specified	Uncertain significance (Jun 22, 2024)
17-4631740-G-A			Benign (Oct 16, 2019)
17-4631754-T-C		not specified	Uncertain significance (Dec 06, 2022)
17-4631763-T-C		not specified	Uncertain significance (Dec 13, 2023)
17-4631891-T-C			Likely benign (Jul 21, 2018)
17-4631895-G-A			Likely benign (Oct 22, 2018)
17-4632003-C-T			Benign (Jul 27, 2018)
17-4632014-G-A		not specified	Uncertain significance (Dec 16, 2022)
17-4632019-G-A		Asthma, nasal polyps, and aspirin intolerance	Benign (-)
17-4632197-G-A		not specified	Uncertain significance (Dec 02, 2022)
17-4632201-C-T		not specified	Uncertain significance (Dec 06, 2021)
17-4632276-G-A		not specified	Uncertain significance (Jan 03, 2024)
17-4632927-C-T		not specified	Uncertain significance (Jun 03, 2022)
17-4633137-T-C			Benign (Jul 15, 2018)
17-4633147-G-A		not specified	Uncertain significance (Nov 28, 2023)
17-4633168-G-A		not specified	Uncertain significance (Aug 02, 2021)
17-4633216-G-A		not specified	Uncertain significance (Oct 12, 2022)
17-4633263-G-A		not specified	Uncertain significance (Jul 09, 2021)
17-4633287-A-C			Likely benign (Jul 06, 2018)
17-4633452-T-C		not specified	Uncertain significance (May 31, 2022)
17-4633479-A-G		not specified	Uncertain significance (Jan 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALOX15	protein_coding	protein_coding	ENST00000570836	14	11393

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.14e-23	0.000552	125472	1	275	125748	0.00110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0277	378	380	0.996	0.0000213	4264
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00485	0.00484
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000714	0.000707
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000762	0.000756
Middle Eastern	0.000714	0.000707
South Asian	0.00157	0.00154
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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);Etodolac Action Pathway;Ketoprofen Action Pathway;Ibuprofen Action Pathway;Rofecoxib Action Pathway;Acetylsalicylic Acid Action Pathway;Diflunisal Action Pathway;Leukotriene C4 Synthesis Deficiency;Acetaminophen Action Pathway;Celecoxib Action Pathway;Sulindac Action Pathway;Diclofenac Action Pathway;Ketorolac Action Pathway;Naproxen Action Pathway;Etoricoxib Action Pathway;Carprofen Action Pathway;Flurbiprofen Action Pathway;Fenoprofen Action Pathway;Antrafenine Action Pathway;Antipyrine Action Pathway;Lumiracoxib Action Pathway;Magnesium salicylate Action Pathway;Trisalicylate-choline Action Pathway;Nepafenac Action Pathway;Phenylbutazone Action Pathway;Lornoxicam Action Pathway;Salsalate Action Pathway;Tenoxicam Action Pathway;Tiaprofenic Acid Action Pathway;Tolmetin Action Pathway;Salicylic Acid Action Pathway;Salicylate-sodium Action Pathway;Oxaprozin Action Pathway;Valdecoxib Action Pathway;Nabumetone Action Pathway;Indomethacin Action Pathway;Meloxicam Action Pathway;Suprofen Action Pathway;Bromfenac Action Pathway;Mefenamic Acid Action Pathway;Arachidonic Acid Metabolism;Piroxicam Action Pathway;Eicosanoid Synthesis;Interleukin-4 and 13 signaling;Metabolism of lipids;Prostaglandin Leukotriene metabolism;Synthesis of Leukotrienes (LT) and Eoxins (EX);Synthesis of 15-eicosatetraenoic acid derivatives;Synthesis of 12-eicosatetraenoic acid derivatives;Arachidonic acid metabolism;Metabolism;Biosynthesis of E-series 18(S)-resolvins;Biosynthesis of E-series 18(R)-resolvins;Biosynthesis of EPA-derived SPMs;Biosynthesis of protectins;Biosynthesis of DHA-derived SPMs;Biosynthesis of DPAn-6 SPMs;Biosynthesis of DPAn-3-derived protectins and resolvins;Biosynthesis of DPAn-3 SPMs;Biosynthesis of DPA-derived SPMs;Biosynthesis of specialized proresolving mediators (SPMs);Fatty acid metabolism;Linoleate metabolism;Prostaglandin formation from arachidonate;Prostaglandin formation from dihomo gama-linoleic acid;Putative anti-Inflammatory metabolites formation from EPA;lipoxin biosynthesis;IL4-mediated signaling events;Arachidonic acid metabolism;resolvin D biosynthesis (Consensus)

Recessive Scores

• pRec: 0.245

Intolerance Scores

• loftool: 0.935
• rvis_EVS: -0.13
• rvis_percentile_EVS: 44.05

Haploinsufficiency Scores

• pHI: 0.0936
• hipred: N
• hipred_score: 0.180

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.809

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alox15
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; neoplasm; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype

Gene ontology

• Biological process: ossification;negative regulation of adaptive immune response;phosphatidylethanolamine biosynthetic process;leukotriene metabolic process;inflammatory response;positive regulation of cell-substrate adhesion;cytokine-mediated signaling pathway;arachidonic acid metabolic process;lipoxygenase pathway;bone mineralization;positive regulation of actin filament polymerization;positive regulation of heterotypic cell-cell adhesion;response to endoplasmic reticulum stress;regulation of peroxisome proliferator activated receptor signaling pathway;cellular response to interleukin-13;wound healing;long-chain fatty acid biosynthetic process;apoptotic cell clearance;hepoxilin biosynthetic process;oxidation-reduction process;positive regulation of ERK1 and ERK2 cascade;cellular response to calcium ion;regulation of engulfment of apoptotic cell;lipoxin A4 biosynthetic process
• Cellular component: lipid droplet;cytosol;plasma membrane;membrane;extrinsic component of cytoplasmic side of plasma membrane
• Molecular function: arachidonate 12-lipoxygenase activity;iron ion binding;protein binding;phosphatidylinositol-4,5-bisphosphate binding;hepoxilin-epoxide hydrolase activity;arachidonate 15-lipoxygenase activity;hepoxilin A3 synthase activity;eoxin A4 synthase activity