ALOX15B

Summary

ALOX15B (arachidonate 15-lipoxygenase type B, HGNC:434) is a protein-coding gene on chromosome 17p13.1, encoding Polyunsaturated fatty acid lipoxygenase ALOX15B (O15296). Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids (PUFAs) generating a spectrum of bioactive lipid mediators.

This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 247 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 137 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001141

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:434
Approved symbol	ALOX15B
Name	arachidonate 15-lipoxygenase type B
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	15-LOX-2
Ensembl gene	ENSG00000179593
Ensembl biotype	protein_coding
OMIM	603697
Entrez	247

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000380173, ENST00000380183, ENST00000571240, ENST00000572022, ENST00000573359, ENST00000944447, ENST00000944448

RefSeq mRNA: 3 — MANE Select: NM_001141 NM_001039130, NM_001039131, NM_001141

CCDS: CCDS11128, CCDS32558, CCDS32559

Canonical transcript exons

ENST00000380183 — 14 exons

Exon	Start	End
ENSE00001241781	8042781	8042884
ENSE00001241792	8042369	8042491
ENSE00002684089	8039059	8039302
ENSE00003462789	8039386	8039605
ENSE00003466155	8047564	8047664
ENSE00003515575	8045238	8045384
ENSE00003541733	8047745	8047915
ENSE00003548566	8048386	8049134
ENSE00003564058	8046907	8047076
ENSE00003589047	8039902	8039983
ENSE00003634291	8044829	8045001
ENSE00003637113	8045483	8045686
ENSE00003648469	8047258	8047379
ENSE00003660586	8046668	8046754

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 96.51.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1753 / max 137.2251, expressed in 304 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159453	2.0109	290
159454	0.0901	46
159452	0.0743	36

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	96.51	gold quality
lower esophagus mucosa	UBERON:0035834	91.99	gold quality
esophagus mucosa	UBERON:0002469	90.44	gold quality
upper arm skin	UBERON:0004263	89.63	gold quality
mammalian vulva	UBERON:0000997	89.11	gold quality
cervix squamous epithelium	UBERON:0006922	88.59	gold quality
prostate gland	UBERON:0002367	87.29	gold quality
right lung	UBERON:0002167	86.29	gold quality
nipple	UBERON:0002030	85.45	gold quality
vagina	UBERON:0000996	83.29	gold quality
skin of leg	UBERON:0001511	83.29	gold quality
zone of skin	UBERON:0000014	82.76	gold quality
skin of abdomen	UBERON:0001416	82.54	gold quality
cervix epithelium	UBERON:0004801	82.40	gold quality
upper lobe of lung	UBERON:0008948	81.33	gold quality
upper lobe of left lung	UBERON:0008952	81.15	gold quality
lower lobe of lung	UBERON:0008949	80.03	gold quality
epithelium of esophagus	UBERON:0001976	78.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.04	gold quality
buccal mucosa cell	CL:0002336	77.81	gold quality
squamous epithelium	UBERON:0006914	76.79	gold quality
esophagus squamous epithelium	UBERON:0006920	76.65	gold quality
lung	UBERON:0002048	75.71	gold quality
gingival epithelium	UBERON:0001949	74.85	gold quality
esophagus	UBERON:0001043	74.34	gold quality
gingiva	UBERON:0001828	73.26	gold quality
penis	UBERON:0000989	73.10	gold quality
oviduct epithelium	UBERON:0004804	72.09	gold quality
body of stomach	UBERON:0001161	71.21	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	24.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR3C1, SP1, SP2, SP3

miRNA regulators (miRDB)

24 targeting ALOX15B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-410-5P	96.55	66.28	459
HSA-MIR-4256	96.22	67.70	669
HSA-MIR-323B-5P	96.12	66.39	472
HSA-MIR-11181-5P	96.12	67.46	665
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-494-5P	95.31	66.29	463

Literature-anchored findings (GeneRIF, showing 35)

• a negative cell cycle regulator in normal prostate epithelial cells, but not present in prostatic neoplasms (PMID:11839751)
• 15-LOX-2 expression is lost in esophageal cancers and the induction of 15-LOX-2 can inhibit cancer cell proliferation (PMID:12659684)
• 15-LOX2 and its splice variants suppress prostate tumor development (PMID:12704195)
• Sp1 and Sp3 proteins play a physiologically important role in positively and negatively regulating the 15-LOX2 gene expression, respectively. (PMID:15247906)
• angiotensin II upregulates LOX-1 and 12-LO and 15-LO expression in human vascular smooth muscle cells (PMID:15797645)
• feedback mechanisms may contribute to the loss of 15-LOX-2 pathway components, which coincide with an increase in PPAR-gamma in many epithelial cancers (PMID:15799828)
• Reduction of isoforms of 15-lipoxygenase (15-LOX)-1 and 15-LOX-2 in human breast cancer (PMID:16556493)
• Crosstalk mechanisms exist between the 15-LOX-2 gene and peroxisome proliferator-activated receptor gamma (PPARgamma) to counterbalance expression and help explain the inverse relationship of these genes in normal prostate versus prostate cancer cells. (PMID:16682954)
• Loss of heterozygosity on 17p13 and down-regulation of ALOX15B can be used to discriminate adrenal cortex neoplasms from adrenocortical adenoma. (PMID:18156936)
• 13-(S)-hydroxyoctadecadienoic acid (13-HODE) is docked to solvent-exposed histidines of a 15-hLOX-2 homology model and found to bind well with histidine627, suggesting a potential location for the allosteric site. (PMID:19645454)
• Expression of 8S-LOX and 15S-LOX-2 suppresses CRD-BP/IMP-1 expression, resulting in inhibition of human prostate carcinoma PC-3 cell proliferation. (PMID:19661680)
• Results from this study suggest a 125-bp region (-157 to -33) is critical for the 15-LOX-2 promoter activity in prostate epithelial cells and cancer cells (PMID:20428779)
• White tea extract induces apoptosis via PPAR gamma and 15-lipoxygenases. (PMID:20668019)
• In summary, we observed associations between high ALOX15B expression in carotid lesions and a history of cerebrovascular symptoms. (PMID:21316676)
• Tumor-associated macrophages isolated from RCC tumors had a high 15-LOX2 expression and secreted substantial amounts of 15(S)-hydroxyeicosatetraenoic acid. (PMID:21900394)
• The C2-domain is not essential for catalytic activity and does hardly impact reaction specificity. (PMID:21951814)
• Data indicate that expressions of 15-LO-1 and 15-LO-2 in placentas and umbilical artery (HUA) rings in preeclampsia (PE) increased more than that in normal groups. (PMID:22078795)
• ALOX15B is the mainly expressed 12/15-lipoxygenase in human macrophages and that its expression is induced by IL-4, LPS and hypoxia. (PMID:22980500)
• The ALOX15B gene may be associated with coronary artery disease. (PMID:24373925)
• Positive feedback-loop of TERT and 15-lipoxygenase-2 promotes pulmonary hypertension. (PMID:24376652)
• Presented is the crystal structure of 15-LOX-2 in complex with an inhibitor that appears to bind as a substrate mimic. 15-LOX-2 contains a long loop, composed of hydrophobic amino acids, which projects from the amino-terminal membrane-binding domain. (PMID:24497644)
• activated ALOX15B in macrophages may play a role in the induction of atherothrombotic events by increasing platelet aggregation and thrombin generation (PMID:24533104)
• 15-LOX2 expression inhibits Myc-induced prostate cancer development, such that in the 3-month- and 6-month-old double transgenic mice, there is a significant reduction in prostate intraneoplasia. (PMID:24732589)
• ALOX15 rs11568070 polymorphisms did not discriminate for the disease or its severity. (PMID:24975552)
• Hpoxia-induced pulmonary vascular remodeling is associated with increased levels of 15-LO-2. (PMID:25895668)
• This study combined molecular dynamics simulations, QM/MM calculations, and umbrella sampling free energy simulations to study the hydrogen atom abstraction from arachidonic acid catalyzed by the human enzyme 15-lipoxygenase-2. (PMID:26918937)
• these results demonstrate the strict regiospecificity of h15-LOX-2 that circumscribes its role in transcellular synthesis. (PMID:27145229)
• 15-LOX-2 is distributed at the plasma membrane when cells are stimulated by the addition Ca(2+) ionophore and that cellular localization is dependent upon the presence of a putative membrane insertion loop. (PMID:27435673)
• Ca(2+) binding induces major structural changes in the 15-lipoxygenase-2 PLAT domain. (PMID:28809482)
• Results demonstrate the expression of ALOX15 and ALOX15B in failing as well as in donor hearts. ALOX15/B signaling may play an important role in heart disease, including heart failure. Isolated fibroblasts from all four chambers of the heart expressed ALOX15 as well as ALOX15B, and gene expression levels were further increased under hypoxia. (PMID:30138423)
• we identified a novel role for ALOX15B, and to a lesser extent ALOX15, in cholesterol homeostasis and CCL17 production in human macrophages. (PMID:30197642)
• ALOX15B expression and up-regulation in the functional and non-functional pituitary adenomas. (PMID:31288808)
• Low 15-LOX-2 expression is associated with lung carcinogenesis. (PMID:31420013)
• 15-lipoxygenase and cyclooxygenase expression profile and their related modulators in COVID-19 infection. (PMID:37716021)
• ALOX15B controls macrophage cholesterol homeostasis via lipid peroxidation, ERK1/2 and SREBP2. (PMID:38581859)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Alox8	ENSMUSG00000020891
rattus_norvegicus	Alox15b	ENSRNOG00000007778

Paralogs (5): ALOX5 (ENSG00000012779), ALOX12 (ENSG00000108839), ALOX15 (ENSG00000161905), ALOXE3 (ENSG00000179148), ALOX12B (ENSG00000179477)

Protein

Protein identifiers

Polyunsaturated fatty acid lipoxygenase ALOX15B — O15296 (reviewed: O15296)

Alternative names: 15-lipoxygenase 2, Arachidonate 15-lipoxygenase B, Arachidonate 15-lipoxygenase type II, Linoleate 13-lipoxygenase 15-LOb

All UniProt accessions (2): I3L1D5, O15296

UniProt curated annotations — full annotation on UniProt →

Function. Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids (PUFAs) generating a spectrum of bioactive lipid mediators. It inserts peroxyl groups at C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing (15S)-hydroperoxyeicosatetraenoate/(15S)-HPETE. Also peroxidizes linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate/13-HPODE. Oxygenates arachidonyl derivatives such as 2-arachidonoylglycerol (2-AG) leading to the production and extracellular release of 15-hydroxyeicosatetraenoyl glycerol (15-HETE-G) that acts as a peroxisome proliferator-activated receptor alpha agonist. Has the ability to efficiently class-switch ALOX5 pro-inflammatory mediators into anti-inflammatory intermediates. Participates in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) resolvin D5 ((7S,17S)-diHPDHA), which can actively down-regulate the immune response and have anti-aggregation properties with platelets. In addition to free PUFAs hydrolyzed from phospholipids, it directly oxidizes PUFAs esterified to membrane-bound phospholipids. Has no detectable 8S-lipoxygenase activity on arachidonate but reacts with (8S)-HPETE to produce (8S,15S)-diHPETE. May regulate progression through the cell cycle and cell proliferation. May also regulate cytokine secretion by macrophages and therefore play a role in the immune response. May also regulate macrophage differentiation into proatherogenic foam cells. Does not convert arachidonic acid to 15S-hydroperoxyeicosatetraenoic acid/(15S)-HPETE.

Subcellular location. Nucleus Cytoplasm. Cytosol. Cell membrane. Cytoplasm. Cytoskeleton. Membrane. Cell junction. Adherens junction. Focal adhesion.

Tissue specificity. Expressed in hair, prostate, lung, ovary, lymph node, spinal cord and cornea.

Cofactor. Binds 1 Fe cation per subunit.

Domain organisation. The PLAT domain can bind calcium ions; this promotes association with membranes.

Induction. Up-regulated by UV-irradiation.

Pathway. Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.

Similarity. Belongs to the lipoxygenase family.

Isoforms (4)

UniProt ID	Names	Canonical?
O15296-1	A, 15-LOb1	yes
O15296-2	B, 15-LOX2sv-b
O15296-3	C, 15-LOX2sv-c
O15296-4	D, 15-LOX2sv-a, 15-LOb2

RefSeq proteins (3): NP_001034219, NP_001034220, NP_001132* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000907	LipOase	Family
IPR001024	PLAT/LH2_dom	Domain
IPR001885	LipOase_mml	Family
IPR013819	LipOase_C	Domain
IPR020833	LipOase_Fe_BS	Binding_site
IPR020834	LipOase_CS	Conserved_site
IPR036226	LipOase_C_sf	Homologous_superfamily
IPR036392	PLAT/LH2_dom_sf	Homologous_superfamily
IPR042062	PLAT_LOX_verte	Domain

Pfam: PF00305, PF01477

Enzyme classification (BRENDA):

• EC 1.13.11.33 — arachidonate 15-lipoxygenase (BRENDA: 27 organisms, 136 substrates, 653 inhibitors, 65 Km, 54 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ARACHIDONIC ACID	0.0025–1.1	15
O2	0.0052–4.2	10
ARACHIDONATE	0.0009–0.013	8
LINOLEIC ACID	0.003–0.0772	7
5S-HYDROPEROXY-6E,8Z,10E,14Z-EICOSATETRAENOIC AC	0.0017–0.057	3
5S-HYDROXY-6E,8Z,10E,14Z-EICOSATETRAENOIC ACID	0.0017–0.029	3
(16(R),5Z,8Z,11Z,14Z)-16-HYDROXYEICOSA-5,8,11,14	0.0289–0.136	2
(16(S),5Z,8Z,11Z,14Z)-16-HYDROXYEICOSA-5,8,11,14	0.0227–0.0236	2
(17(R),5Z,8Z,11Z,14Z)-17-HYDROXYEICOSA-5,8,11,14	0.0368–0.293	2
(17(S),5Z,8Z,11Z,14Z)-17-HYDROXYEICOSA-5,8,11,14	0.0313–0.236	2
4Z,7Z,10Z,12E,16Z,19Z-DOCOSAHEXAENOIC ACID	0.0009–0.0067	2
1-LINOLEOYL LYSOPHOSPHATIDIC ACID	0.0083	1
1-LINOLEOYL LYSOPHOSPHATIDYLCHOLINE	0.0175	1
DILINOLEOYL PHOSPHATIDIC ACID	0.09	1
DILINOLEOYL PHOSPHATIDYLCHOLINE	0.0717	1

Catalyzed reactions (Rhea), 12 shown:

• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (RHEA:16869)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 15-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (RHEA:48832)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 5-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (RHEA:48844)
• (9Z,12Z)-octadecadienoate + O2 = 13-hydroperoxy-(9Z,11E)-octadecadienoate (RHEA:48848)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-taurine + O2 = N-(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-taurine (RHEA:50156)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate + O2 = N-(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-gamma-aminobutanoate (RHEA:50180)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-L-alanine + O2 = N-(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-alanine (RHEA:50184)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + O2 = N-(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-glycine (RHEA:50188)
• (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate + O2 = (8S,15S)-dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate (RHEA:50932)
• 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + O2 = 2-[15(S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-glycerol (RHEA:53332)
• (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + O2 = (5S,15S)-dihydroperoxy-(6E,8Z,11Z,13E)-eicosatetraenoate (RHEA:53652)
• (5S,6R)-dihydroxy-(7E,9E,11Z,14Z)-eicosatetraenoate + O2 = (5S,6R)-dihydroxy-(15S)-hydroperoxy-(7E,9E,11Z,13E)-eicosatetraenoate (RHEA:53656)

UniProt features (85 total): helix 31, strand 16, binding site 12, turn 8, mutagenesis site 5, splice variant 4, sequence variant 4, domain 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8VIY	X-RAY DIFFRACTION	2.34
7LAF	X-RAY DIFFRACTION	2.44
4NRE	X-RAY DIFFRACTION	2.63

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15296-F1	95.24	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (12): 86; 373; 378; 553; 676; 15; 17; 39; 40; 42; 44; 85

Mutagenesis-validated functional residues (5):

Position	Phenotype
39	abolishes calcium-dependent association with membranes; when associated with a-44 and a-85.
44	abolishes calcium-dependent association with membranes; when associated with a-39 and a-85.
85	abolishes calcium-dependent association with membranes; when associated with a-39 and a-44.
602	no effect on the stereoselectivity of the oxygenation reaction. completely changes the stereoselectivity of the oxygenat
603	changes the stereoselectivity of the oxygenation reaction. completely changes the stereoselectivity of the oxygenation r

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2142770	Synthesis of 15-eicosatetraenoic acid derivatives
R-HSA-1430728	Metabolism
R-HSA-2142753	Arachidonate metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 215 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_GROWTH, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_DERIVED_FOAM_CELL_DIFFERENTIATION, CHANDRAN_METASTASIS_DN, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (21): lipid metabolic process (GO:0006629), phospholipid metabolic process (GO:0006644), apoptotic process (GO:0006915), negative regulation of cell population proliferation (GO:0008285), positive regulation of macrophage derived foam cell differentiation (GO:0010744), arachidonate metabolic process (GO:0019369), lipoxygenase pathway (GO:0019372), negative regulation of cell migration (GO:0030336), prostate gland development (GO:0030850), regulation of epithelial cell differentiation (GO:0030856), positive regulation of chemokine production (GO:0032722), lipid oxidation (GO:0034440), positive regulation of peroxisome proliferator activated receptor signaling pathway (GO:0035360), linoleic acid metabolic process (GO:0043651), positive regulation of keratinocyte differentiation (GO:0045618), negative regulation of cell cycle (GO:0045786), negative regulation of growth (GO:0045926), hepoxilin biosynthetic process (GO:0051122), endocannabinoid signaling pathway (GO:0071926), cannabinoid biosynthetic process (GO:1901696), lipoxin A4 biosynthetic process (GO:2001303)

GO Molecular Function (12): iron ion binding (GO:0005506), calcium ion binding (GO:0005509), lipid binding (GO:0008289), linoleate 13S-lipoxygenase activity (GO:0016165), arachidonate 8(S)-lipoxygenase activity (GO:0036403), arachidonate 15-lipoxygenase activity (GO:0050473), linoleate 9S-lipoxygenase activity (GO:1990136), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (10): nucleus (GO:0005634), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), membrane (GO:0016020), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Arachidonate metabolism	1
Fatty acid metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	4
cellular anatomical structure	3
negative regulation of cellular process	2
long-chain fatty acid metabolic process	2
icosanoid metabolic process	2
unsaturated fatty acid metabolic process	2
olefinic compound metabolic process	2
binding	2
primary metabolic process	1
lipid metabolic process	1
organophosphate metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
fatty acid metabolic process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
urogenital system development	1
reproductive structure development	1
gland development	1
epithelial cell differentiation	1
regulation of cell differentiation	1
regulation of multicellular organismal development	1
positive regulation of cytokine production	1
chemokine production	1
regulation of chemokine production	1
lipid modification	1
peroxisome proliferator activated receptor signaling pathway	1
regulation of peroxisome proliferator activated receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
keratinocyte differentiation	1
positive regulation of epidermal cell differentiation	1
regulation of keratinocyte differentiation	1
positive regulation of multicellular organismal process	1

Protein interactions and networks

STRING

894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALOX15B	LOX	P28300	817
ALOX15B	PEBP1	P30086	648
ALOX15B	ALOX5AP	P20292	491
ALOX15B	ACSL4	O60488	447
ALOX15B	LTA4H	P09960	446
ALOX15B	GPX4	P36969	433
ALOX15B	PTGS2	P35354	424
ALOX15B	LPCAT3	Q6P1A2	419
ALOX15B	OLR1	P78380	415
ALOX15B	PTGS1	P23219	406
ALOX15B	PPARG	P37231	373
ALOX15B	GGT1	P19440	358
ALOX15B	LTC4S	Q16873	357
ALOX15B	SPRR2E	P22531	352
ALOX15B	PLA2G4A	P47712	350

IntAct

27 interactions, top by confidence:

A	B	Type	Score
ALOX15B	VMA22	psi-mi:“MI:0915”(physical association)	0.560
ALOX15B	CTAG1A	psi-mi:“MI:0915”(physical association)	0.560
ALOX15B	TRIM21	psi-mi:“MI:0915”(physical association)	0.560
ALOX15B	KCNF1	psi-mi:“MI:0915”(physical association)	0.560
ALOX15B	TRAIP	psi-mi:“MI:0915”(physical association)	0.560
ALOX15B	RARA	psi-mi:“MI:0915”(physical association)	0.560
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
PTDSS1	IGLL5	psi-mi:“MI:0914”(association)	0.350
FERMT2	ALOX15B	psi-mi:“MI:0914”(association)	0.350
ALOX15B	TAF5L	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SH2D3A	A2ML1	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
FOXN3	IGLL5	psi-mi:“MI:0914”(association)	0.350
ALOX15B	CTAG1A	psi-mi:“MI:0915”(physical association)	0.000
ALOX15B	TRIM21	psi-mi:“MI:0915”(physical association)	0.000
ALOX15B	KCNF1	psi-mi:“MI:0915”(physical association)	0.000
ALOX15B	TRAIP	psi-mi:“MI:0915”(physical association)	0.000
ALOX15B	RARA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): KBTBD2 (Affinity Capture-MS), RPH3A (Affinity Capture-MS), ALOX15B (Affinity Capture-MS), TAF5L (Affinity Capture-MS), KIF3A (Affinity Capture-MS), ALOX15B (Two-hybrid), ALOX15B (Two-hybrid), ALOX15B (Two-hybrid), ALOX15B (Two-hybrid), TRAIP (Two-hybrid), CTAG1B (Two-hybrid), CTAG1A (Two-hybrid), ALOX15B (Affinity Capture-MS), TAF5L (Affinity Capture-MS), ALOX15B (Affinity Capture-MS)

ESM2 similar proteins: A6H603, D3ZBP4, D3ZKX9, D3ZQF9, F1LQ70, O00329, O00411, O15296, O35936, O43548, O70582, O75342, O95932, P09917, P0C869, P0C871, P12527, P12530, P16050, P16452, P16469, P18054, P27479, P39654, P39655, P48999, P49222, P51399, P52630, P55249, Q02759, Q149M9, Q2KMM4, Q2TB18, Q4R7D0, Q50L43, Q5R5N9, Q5RBE8, Q5RCY5, Q68DD2

Diamond homologs: C8YR32, D3ZKX9, D3ZQF9, F1LQ70, O15296, O16025, O22507, O22508, O24371, O24379, O35936, O70582, O75342, P08170, P09186, P09439, P09917, P09918, P12527, P12530, P16050, P16469, P18054, P24095, P27479, P27480, P27481, P37831, P38414, P38417, P38418, P39654, P39655, P48999, P51399, P55249, Q02759, Q2KMM4, Q41238, Q43190

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

137 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2251 predictions. Top by Δscore:

Variant	Effect	Δscore
17:8039298:GCGCT:G	donor_gain	1.0000
17:8039300:GCT:G	donor_gain	1.0000
17:8039303:G:GG	donor_gain	1.0000
17:8039307:G:GG	donor_gain	1.0000
17:8039975:GAT:G	donor_gain	1.0000
17:8039984:G:GG	donor_gain	1.0000
17:8039989:G:GT	donor_gain	1.0000
17:8039992:G:GT	donor_gain	1.0000
17:8042485:GCTC:G	donor_gain	1.0000
17:8042490:GC:G	donor_gain	1.0000
17:8042492:G:GG	donor_gain	1.0000
17:8042497:G:GT	donor_gain	1.0000
17:8042881:GCTG:G	donor_gain	1.0000
17:8044818:A:AG	acceptor_gain	1.0000
17:8044819:C:G	acceptor_gain	1.0000
17:8044824:TGCA:T	acceptor_loss	1.0000
17:8044824:TGCAG:T	acceptor_gain	1.0000
17:8044825:GCAG:G	acceptor_loss	1.0000
17:8044826:CA:C	acceptor_loss	1.0000
17:8044826:CAG:C	acceptor_gain	1.0000
17:8044827:A:AG	acceptor_gain	1.0000
17:8044827:AGA:A	acceptor_gain	1.0000
17:8044828:G:GA	acceptor_gain	1.0000
17:8044828:G:GC	acceptor_loss	1.0000
17:8044828:GA:G	acceptor_gain	1.0000
17:8044828:GAG:G	acceptor_gain	1.0000
17:8044828:GAGC:G	acceptor_gain	1.0000
17:8044990:GC:G	donor_gain	1.0000
17:8045000:AGG:A	donor_loss	1.0000
17:8045002:G:T	donor_loss	1.0000

AlphaMissense

4402 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:8045557:G:C	K357N	0.991
17:8045557:G:T	K357N	0.991
17:8045568:G:C	R361P	0.977
17:8045553:C:A	A356D	0.976
17:8046717:G:C	R417P	0.976
17:8045573:G:C	A363P	0.974
17:8045516:T:C	F344L	0.971
17:8045518:C:A	F344L	0.971
17:8045518:C:G	F344L	0.971
17:8045543:T:A	W353R	0.970
17:8045543:T:C	W353R	0.970
17:8045545:G:C	W353C	0.970
17:8045545:G:T	W353C	0.970
17:8045579:T:C	F365L	0.970
17:8045581:C:A	F365L	0.970
17:8045581:C:G	F365L	0.970
17:8042827:T:A	W207R	0.968
17:8042827:T:C	W207R	0.968
17:8044940:T:A	V263D	0.968
17:8045561:T:A	W359R	0.968
17:8045561:T:C	W359R	0.968
17:8045380:T:A	I331N	0.963
17:8047760:T:A	W566R	0.963
17:8047760:T:C	W566R	0.963
17:8045250:T:C	F288L	0.961
17:8045252:C:A	F288L	0.961
17:8045252:C:G	F288L	0.961
17:8044864:T:C	F238L	0.958
17:8044866:C:A	F238L	0.958
17:8044866:C:G	F238L	0.958

dbSNP variants (sampled 300 via entrez): RS1000478509 (17:8046741 AG>A), RS1001108602 (17:8039464 C>T), RS1001268361 (17:8042574 C>A), RS1001547213 (17:8041602 A>G), RS1001561370 (17:8039217 A>G), RS1001598704 (17:8047161 G>A,T), RS1001937318 (17:8046171 C>T), RS1002162066 (17:8038143 C>CT), RS1002214627 (17:8037865 A>C), RS1002221650 (17:8044119 G>A), RS1002228756 (17:8041897 T>A,C), RS1002282581 (17:8040269 C>T), RS1002322714 (17:8043805 A>G), RS1002370889 (17:8049172 C>T), RS1002515079 (17:8040701 T>G)

Disease associations

OMIM: gene MIM:603697 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002541_111	Menarche (age at onset)	2.000000e-08
GCST006585_2236	Blood protein levels	2.000000e-09
GCST009391_1976	Metabolite levels	5.000000e-06
GCST010463_25	Childhood ALL/LBL (acute lymphoblastic leukemia/lymphoblastic lymphoma) treatment-related venous thromboembolism	4.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0008534	tryptophan measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2457 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,792 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1200596	CHLOROXINE	4	1,792

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Lipoxygenases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 21n [PMID: 17656086]	Inhibition	7.29	pIC50
MLS000536924	Inhibition	5.6	pKi

ChEMBL bioactivities

16 potent at pChembl≥5 of 28 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.29	IC50	51	nM	CHEMBL235920
6.83	IC50	147	nM	CHEMBL399821
6.47	IC50	340	nM	CHEMBL1390514
6.40	IC50	402	nM	CHEMBL392977
6.36	IC50	433	nM	CHEMBL391659
6.28	IC50	530	nM	CHEMBL1520238
6.22	EC50	600	nM	CHEMBL1452107
6.12	EC50	750	nM	CHEMBL1390514
6.06	IC50	870	nM	CHEMBL1352020
5.89	EC50	1300	nM	CHEMBL1352020
5.58	IC50	2600	nM	CHEMBL1489870
5.51	IC50	3100	nM	CHEMBL1452107
5.50	IC50	3130	nM	CHEMBL401246
5.08	IC50	8300	nM	CHEMBL239893

PubChem BioAssay actives

15 with measured affinity, of 211 total; 11 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[2-[[ethyl-[(3R)-1-[1-(4-fluorophenyl)ethyl]pyrrolidin-3-yl]sulfamoyl]amino]ethyl]-4-(4-methoxyphenyl)-2-thiophen-2-yl-1H-imidazole	300785: Inhibition of human recombinant 15-lipoxygenase over-expressed in CHO cells	ic50	0.0510	uM
N-[2-[4-(4-methoxyphenyl)-2-thiophen-2-yl-1H-imidazol-5-yl]ethyl]-4-pentylbenzenesulfonamide	300785: Inhibition of human recombinant 15-lipoxygenase over-expressed in CHO cells	ic50	0.1470	uM
1-phenyl-2-[[4-(trifluoromethyl)phenyl]methylsulfanyl]imidazole	1766300: Inhibition of human 15-LOX-2 assessed as enzymatic rate using arachidonic acid as substrate by UV/Vis spectrophotometric analysis	ic50	0.3400	uM
N-[2-[4-(4-methoxyphenyl)-2-phenyl-1H-imidazol-5-yl]ethyl]-4-pentylbenzenesulfonamide	300785: Inhibition of human recombinant 15-lipoxygenase over-expressed in CHO cells	ic50	0.4020	uM
4-(3,4-dichlorophenyl)-N-[2-[4-(4-methoxyphenyl)-2-thiophen-2-yl-1H-imidazol-5-yl]ethyl]piperazine-1-sulfonamide	300785: Inhibition of human recombinant 15-lipoxygenase over-expressed in CHO cells	ic50	0.4330	uM
2-[(4-bromophenyl)methylsulfanyl]-1-phenylimidazole	1766300: Inhibition of human 15-LOX-2 assessed as enzymatic rate using arachidonic acid as substrate by UV/Vis spectrophotometric analysis	ic50	0.5300	uM
3-[(4-methylphenyl)methylsulfanyl]-1-phenyl-1,2,4-triazole	1766313: Inhibition of human 15-LOX-2 expressed in HEK293T cells assessed as a reduction in 15-HETE production using arachidonic acid as substrate incubated for 20 mins	ec50	0.6000	uM
2-[(4-ethylphenyl)methylsulfanyl]-1-phenylimidazole	1766300: Inhibition of human 15-LOX-2 assessed as enzymatic rate using arachidonic acid as substrate by UV/Vis spectrophotometric analysis	ic50	0.8700	uM
2-(4-chlorophenyl)-5-cyclohexyl-1,3,4-oxadiazole	1766300: Inhibition of human 15-LOX-2 assessed as enzymatic rate using arachidonic acid as substrate by UV/Vis spectrophotometric analysis	ic50	2.6000	uM
5-[2-[[[(3R)-1-benzylpyrrolidin-3-yl]-methylsulfamoyl]amino]ethyl]-4-(4-methoxyphenyl)-2-phenyl-1H-imidazole	300785: Inhibition of human recombinant 15-lipoxygenase over-expressed in CHO cells	ic50	3.1300	uM
3-(3-methylphenyl)-3,4-dihydro-2H-chromene-6,7-diol	1801111: IC50 Assay from Article 10.1111/cbdd.12469: “Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5-Lipo-Oxygenase.”	ic50	8.3000	uM

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects splicing	2
Benzo(a)pyrene	increases expression, increases methylation	2
Progesterone	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression, increases expression	2
lead acetate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, increases expression, affects cotreatment	1
cupric chloride	decreases expression	1
rofecoxib	affects expression	1
entinostat	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Calcitriol	affects cotreatment, increases expression	1
Carmustine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression, increases expression	1
Sodium Fluoride	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Isotretinoin	decreases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases expression	1

ChEMBL screening assays

34 unique, capped per target: 29 binding, 3 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1273493	Binding	Inhibition of human N-terminal His6-tagged epithelial 15-lipoxygenase-2 after 15 mins by UV-vis spectrophotometer analysis	Discovery of potent and selective inhibitors of human reticulocyte 15-lipoxygenase-1. — J Med Chem
CHEMBL1613800	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of 15-hLO-2 (15-human lipoxygenase 2). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2312, AID2537, AID2702]	PubChem BioAssay data set
CHEMBL4825400	ADMET	Pseudo-peroxidase activity in human 15-LOX-2 assessed as redox activity of the compound by measuring degradation of 13-HpODE at 20 uM by UV/Vis pseudo-peroxidase assay	Kinetic and structural investigations of novel inhibitors of human epithelial 15-lipoxygenase-2. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7ZT	HAP1 ALOX15B (-) 1	Cancer cell line	Male
CVCL_C7ZU	HAP1 ALOX15B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.