ALOX12

Summary

ALOX12 (arachidonate 12-lipoxygenase, 12S type, HGNC:429) is a protein-coding gene on chromosome 17p13.1, encoding Polyunsaturated fatty acid lipoxygenase ALOX12 (P18054). Catalyzes the regio and stereo-specific incorporation of molecular oxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species.

This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on different polyunsaturated fatty acid substrates to generate bioactive lipid mediators including eicosanoids and lipoxins. The encoded enzyme and its reaction products have been shown to regulate platelet function. Elevated expression of this gene has been observed in pancreatic islets derived from human diabetes patients. Allelic variants in this gene may be associated with susceptibility to toxoplasmosis. Multiple pseudogenes of this gene have been identified in the human genome.

Source: NCBI Gene 239 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 117 total — 1 pathogenic
• Druggable target: yes — 58 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000697

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:429
Approved symbol	ALOX12
Name	arachidonate 12-lipoxygenase, 12S type
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	12S-LOX
Ensembl gene	ENSG00000108839
Ensembl biotype	protein_coding
OMIM	152391
Entrez	239

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000251535, ENST00000406228, ENST00000480801, ENST00000915595

RefSeq mRNA: 1 — MANE Select: NM_000697 NM_000697

CCDS: CCDS11084

Canonical transcript exons

ENST00000251535 — 14 exons

Exon	Start	End
ENSE00000680256	6996826	6997027
ENSE00000680260	6998953	6999056
ENSE00000887238	7005858	7006027
ENSE00000887240	7006486	7006607
ENSE00000905333	6999306	6999466
ENSE00000905334	7000336	7000479
ENSE00000905335	7001602	7001811
ENSE00000905338	7005257	7005343
ENSE00000949160	7009747	7009847
ENSE00001150037	6996049	6996252
ENSE00002776425	6998715	6998837
ENSE00002875993	6998509	6998590
ENSE00003587638	7010244	7010754
ENSE00003660105	7009956	7010126

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 99.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5235 / max 209.6574, expressed in 78 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159076	0.3380	63
159077	0.1855	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.14	gold quality
amniotic fluid	UBERON:0000173	97.63	gold quality
tongue squamous epithelium	UBERON:0006919	95.77	gold quality
buccal mucosa cell	CL:0002336	95.31	gold quality
cervix squamous epithelium	UBERON:0006922	93.39	gold quality
cervix epithelium	UBERON:0004801	92.48	gold quality
monocyte	CL:0000576	89.68	gold quality
esophagus mucosa	UBERON:0002469	89.49	gold quality
mononuclear cell	CL:0000842	89.20	gold quality
leukocyte	CL:0000738	88.34	gold quality
epithelium of esophagus	UBERON:0001976	88.08	gold quality
squamous epithelium	UBERON:0006914	87.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.04	gold quality
esophagus squamous epithelium	UBERON:0006920	87.03	gold quality
gingiva	UBERON:0001828	86.28	gold quality
vagina	UBERON:0000996	85.84	gold quality
oral cavity	UBERON:0000167	84.39	gold quality
skin of abdomen	UBERON:0001416	84.21	gold quality
skin of leg	UBERON:0001511	83.29	gold quality
gingival epithelium	UBERON:0001949	82.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.07	gold quality
zone of skin	UBERON:0000014	81.58	gold quality
uterine cervix	UBERON:0000002	80.87	gold quality
esophagus	UBERON:0001043	80.64	gold quality
ectocervix	UBERON:0012249	80.03	gold quality
blood	UBERON:0000178	78.18	gold quality
granulocyte	CL:0000094	77.17	gold quality
mammalian vulva	UBERON:0000997	77.08	gold quality
pharyngeal mucosa	UBERON:0000355	76.80	gold quality
mouth mucosa	UBERON:0003729	75.85	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	12.39
E-MTAB-7606	no	178.46
E-ANND-3	no	1.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARNT, CEBPZ, FOS, JUN, NFKB1, NR3C1, REL, RUNX1, SP1, SP3, STAT6, TP63, ZHX2

miRNA regulators (miRDB)

32 targeting ALOX12, 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-6870-5P	99.99	68.55	2115
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-4654	95.86	65.72	751

Literature-anchored findings (GeneRIF, showing 40)

• Functional role of extracellular signal-regulated kinase activation and c-Jun induction in phorbol ester-induced promoter activation of human 12(S)-lipoxygenase gene.(12(S)-lipoxygenase) (PMID:11914583)
• 12-Lipoxygenase stimulation leads to aldosterone production in H295R cells in part through activation of CREB/ATF-1 and p38 MAPK pathway. (PMID:12538614)
• a new polymorphism in ALOX12 gene is associated with bipolar disorder. (PMID:12664313)
• The substrates down regulate the activity of this enzyme in platelets. (PMID:12664573)
• Isoenzyme is characterized. (PMID:12664578)
• human breast tumours aberrantly express significantly higher levels of 12-lipoxygenase; levels of 12-lipoxygenase were also particularly high in tumours from patients who died of breast cancer. (PMID:12907138)
• Lipoxygenase is induced in bladder cancer. Results suggest that lipoxygenase inhibitors may mediate potent antiproliferative effects against bladder cancer cells. (PMID:14532840)
• our data suggest that an increase in 12-LOX expression enhances the metastatic potential of human prostate cancer cells. (PMID:14669797)
• increased expressions of 5-LOX and 12-LOX were detected in testicular cancer tissues (PMID:14767568)
• Up-regulation of 12-Lipoxygenase is associated with prostate cancer (PMID:15010818)
• 12/15-lipoxygenase is increased in Alzheimer’s disease and has a possible role in brain oxidative stress (PMID:15111312)
• first detailed intracellular characterization of a specific GP-VI-dependent signaling pathway that acutely activates 12-LOX turnover in human platelets and provides a novel link between immune receptor signaling and lipid oxidation in the vasculature. (PMID:15142951)
• p12-LOX of human melanoma has been shown to be involved in the control of the metastatic phenotype (PMID:15305153)
• Inflammatory cytokines rapidly activate 12LO and induce 12LO translocation. (PMID:15729574)
• angiotensin II upregulates LOX-1 and 12-LO and 15-LO expression in human vascular smooth muscle cells (PMID:15797645)
• Sp1 interacts with Hsp90alpha to recruit it to the promoter of 12(S)-lipoxygenase and then to regulate gene transcription by modulating the binding ability of Sp1 to promoters (PMID:16118214)
• data provide insight into a possible mechanism by which prostate cancer cells with elevated expression of P12-LOX stimulate VEGF production, thus increasing their angiogenic potential (PMID:16482570)
• A nonsynonymous polymorphism in ALOX12 is associated to essential hypertension and to urinary levels of 12(S)-HETE, thus suggesting a role for this gene in this disease. (PMID:16514435)
• Polymorphisms in the ALOX12 gene may contribute to normal variation in spine BMD (PMID:16598376)
• 12-lipoxygenase-mediated stimulation of tumor angiogenesis in prostate cancer (PMID:16638750)
• Boswellic acids induce the release of arachidonic acid and the synthesis of 12-H(P)ETE in human platelets by unique Ca2+-independent routes, and we identified p12-Lipoxygenase as a selective molecular target of boswellic acids. (PMID:16788089)
• The substrate preference of mouse eLOX3 and the unique occurrence of an 8S-LOX enzyme in mouse skin point to a potential LOX pathway for the production of epoxyalcohol in murine epidermal differentiation. (PMID:17045234)
• Inherited polymorphisms in platelet 12-lipoxygenase may confer susceptibility to colorectal cancer in Han Chinese. (PMID:17151091)
• over-expression of 12-lipoxygenase is associated with breast cancer (PMID:17192687)
• an inverse association between the Arg261Gln polymorphism in 12-LOX and colorectal adenoma (OR, 0.63; 95% CI, 0.40-1.00) (PMID:17236225)
• observations suggest a previously unrecognized angiotensin-II dependent protein interaction in VSMC through which 12-LO protein may be trafficked, for yet undiscovered purposes towards the much more abundantly expressed cytoskeletal protein alpha-actin. (PMID:17379189)
• Inherited polymorphisms in arachidonic acid-metabolizing enzymes, which result in heightened gene expression or enzymatic activity, may confer host susceptibility to esophageal squamous cell carcinoma. (PMID:17460548)
• there is no association between polymorphism in ALOX15 and bone mineral density phenotypes, but genetic variation in ALOX12 seems to play a role in determining bone structure in Caucasian women (PMID:17520163)
• presented a novel form of ichthyosis in a patient, termed hepoxilin A(3) synthase-linked ichthyosis (HXALI), whose scales expressed high levels of 12R-LOX, but were deficient of HXA(3) synthase [hepoxilin A3 synthase] (PMID:18086569)
• These results demonstrate a novel mechanism of parathyroid hormone-induced human bone cell proliferation operating through 12- and 15-lipoxygenase enzymes. (PMID:18187376)
• Kinetic isotope effects (KIEs) in the reactions of three human LOs (platelet 12-hLO, reticulocyte 15-hLO-1, and epithelial 15-hLO-2) with arachidonic acid (AA). (PMID:18547056)
• Compared with 261Arg allele carriers, adjusted mean ACR was 42% greater in the 189 carriers of two 261Gln alleles (95% confidence interval, 10 to 83; P = 0.007). (PMID:18640486)
• The effects of UV on 12/15-LOX gene expression in the human keratinocyte cell line, HaCaT, were studied. (PMID:18755188)
• The mechanism and kinetics of the oxydation of arachidonic acid by both 15-lipoxygenase and 12-lipoxygenase was studied using recombinant enzymes. (PMID:19469483)
• The genetic effects of ALOX12 and ALOX15 polymorphisms for developing aspirin-exacerbated respiratory disease may be minimal compared with those of ALOX5. (PMID:19663136)
• Compared enzymatic properties of recombinant enzymes with SNP R261Q in the human platelet 12-lipoxygenase: ‘wild-type’The R261 variant does not follow the same kinetics; the N544L substitution in the active site almost eradicates enzymatic activity. (PMID:19885615)
• Two single-nucleotide polymorphisms, rs9904779 and rs434473 (encodes a replacement of asparagine by serine), of arachidonate 12-lipoxygenase were significantly associated with age at natural menopause (PMID:20061896)
• 12-Lipoxygenase Products Reduce Insulin Secretion and {beta}-Cell Viability in Human Islets. (PMID:20089617)
• ALOX12 is a direct transcriptional target of RUNX1. (PMID:20181616)
• The mRNA levels of ALOX12 implicated pathways differed significantly in gliomas according to the histological type. (PMID:20382140)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	alox12	ENSDARG00000069463
mus_musculus	Alox12	ENSMUSG00000000320
rattus_norvegicus	Alox12	ENSRNOG00000027037

Paralogs (5): ALOX5 (ENSG00000012779), ALOX15 (ENSG00000161905), ALOXE3 (ENSG00000179148), ALOX12B (ENSG00000179477), ALOX15B (ENSG00000179593)

Protein

Protein identifiers

Polyunsaturated fatty acid lipoxygenase ALOX12 — P18054 (reviewed: P18054)

Alternative names: Arachidonate (12S)-lipoxygenase, Arachidonate (15S)-lipoxygenase, Linoleate (13S)-lipoxygenase, Lipoxin synthase 12-LO, Platelet-type lipoxygenase 12

All UniProt accessions (2): P18054, K7ENN9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the regio and stereo-specific incorporation of molecular oxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species. Mainly converts arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to the specific bioactive lipid (12S)-hydroperoxyeicosatetraenoate/(12S)-HPETE. Through the production of bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. It can also catalyze the epoxidation of double bonds of polyunsaturated fatty acids such as (14S)-hydroperoxy-docosahexaenoate/(14S)-HPDHA resulting in the formation of (13S,14S)-epoxy-DHA. Furthermore, it may participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively down-regulate the immune response and have anti-aggregation properties with platelets. An additional function involves a multistep process by which it transforms leukotriene A4/LTA4 into the bioactive lipids lipoxin A4/LXA4 and lipoxin B4/LXB4, both are vasoactive and LXA4 may regulate neutrophil function via occupancy of specific recognition sites. Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to (13S)-hydroperoxyoctadecadienoate/ (13S-HPODE). Due to its role in regulating both the expression of the vascular endothelial growth factor (VEGF, an angiogenic factor involved in the survival and metastasis of solid tumors) and the expression of integrin beta-1 (known to affect tumor cell migration and proliferation), it can be regarded as protumorigenic. Important for cell survival, as it may play a role not only in proliferation but also in the prevention of apoptosis in vascular smooth muscle cells.

Subcellular location. Cytoplasm. Cytosol. Membrane.

Tissue specificity. Expressed in vascular smooth muscle cells.

Disease relevance. Esophageal cancer (ESCR) [MIM:133239] A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to esophageal cancer. Colorectal cancer (CRC) [MIM:114500] A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to colorectal cancer.

Activity regulation. Activated by EGF. Arachidonic acid conversion is inhibited by (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate (13S,14S-epoxy-DHA). Arachidonate 12-lipoxygenase activity is decreased when PH decreases from 7.4 to 6.

Cofactor. Binds 1 Fe cation per subunit.

Induction. Down-regulated upon starvation, by UV-irradiation and 15-lipoxygenase metabolites.

Pathway. Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.

Similarity. Belongs to the lipoxygenase family.

RefSeq proteins (1): NP_000688* (*=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 1.13.11.31 — arachidonate 12-lipoxygenase (BRENDA: 25 organisms, 141 substrates, 194 inhibitors, 60 Km, 34 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ARACHIDONIC ACID	0.004–0.08	14
ARACHIDONATE	0.0009–0.232	8
LINOLEIC ACID	0.0125–0.0312	8
O2	0.0052–7	8
5,8,11,14,17-EICOSAPENTAENOIC ACID	0.003–0.427	4
4Z,7Z,10Z,12E,16Z,19Z-DOCOSAHEXAENOIC ACID	0.0009–0.0067	2
5S-HYDROPEROXY-6E,8Z,10E,14Z-EICOSATETRAENOIC AC	0.0017–0.0078	2
5S-HYDROXY-6E,8Z,10E,14Z-EICOSATETRAENOIC ACID	0.0017–0.0049	2
8,11,14-EICOSATRIENOIC ACID	0.0035–0.079	2
METHYL ARACHIDONATE	0.0114–0.018	2
(Z,Z,Z,E)-5,8,11,13-EICOSATETRAENOIC ACID	0.0039	1
1-LINOLEOYL LYSOPHOSPHATIDIC ACID	0.0355	1
1-LINOLEOYL LYSOPHOSPHATIDYLCHOLINE	0.0151	1
5(S)-HYDROXY-6E,8Z,11Z,14Z-EICOSATETRAENOIC ACID	0.0045	1
5S,15S-DIHYDROPEROXYEICOSATETRAENOIC ACID	—	0

Catalyzed reactions (Rhea), 12 shown:

• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate (RHEA:10428)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (RHEA:16869)
• (9Z,12Z)-octadecadienoate + O2 = (13S)-hydroperoxy-(9Z,11E)-octadecadienoate (RHEA:22780)
• (5Z,8Z,11Z)-eicosatrienoate + O2 = (12S)-hydroperoxy-(5Z,8Z,10E)-eicosatrienoate (RHEA:41324)
• (8Z,11Z,14Z)-eicosatrienoate + O2 = (12S)-hydroperoxy-(8Z,10E,14Z)-eicosatrienoate (RHEA:41328)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)-hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate (RHEA:41332)
• 2 leukotriene A4 + O2 + 2 H2O = 2 lipoxin A4 (RHEA:48584)
• 2 leukotriene A4 + O2 + 2 H2O = 2 lipoxin B4 (RHEA:48588)
• (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = (12S)-hydroperoxy-(5Z,8Z,10E,14Z,17Z)-eicosapentaenoate (RHEA:48704)
• 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-taurine + O2 = N-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-taurine (RHEA:50160)
• N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + O2 = N-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-glycine (RHEA:50168)

UniProt features (82 total): helix 28, strand 22, mutagenesis site 9, sequence variant 6, binding site 5, turn 5, sequence conflict 3, domain 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8GHE	ELECTRON MICROSCOPY	2.05
8GHD	ELECTRON MICROSCOPY	2.2
8GHC	ELECTRON MICROSCOPY	2.3
3D3L	X-RAY DIFFRACTION	2.6
8GHB	ELECTRON MICROSCOPY	2.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18054-F1	95.45	0.90

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 (5): 360; 365; 540; 544; 663

Post-translational modifications (1): 246

Mutagenesis-validated functional residues (9):

Position	Phenotype
355	no effect on arachidonate 12(s)-lipoxygenase activity.
360	complete loss of arachidonate 12(s)-lipoxygenase activity.
365	complete loss of arachidonate 12(s)-lipoxygenase activity.
383	alteredarachidonate 12(s)-lipoxygenase activity and protein expression.
392	no effect on arachidonate 12(s)-lipoxygenase activity.
416	reduced arachidonate 12(s)-lipoxygenase activity. no effect on the stereoselectivity of the oxygenation reaction.
417	reduced arachidonate 12(s)-lipoxygenase activity. alters the stereoselectivity of the oxygenation reaction.
418	no effect onarachidonate 12(s)-lipoxygenase activity. no effect on the stereoselectivity of the oxygenation reaction.
540	complete loss of arachidonate 12(s)-lipoxygenase activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-2142696	Synthesis of Hepoxilins (HX) and Trioxilins (TrX)
R-HSA-2142700	Biosynthesis of Lipoxins (LX)
R-HSA-2142712	Synthesis of 12-eicosatetraenoic acid derivatives
R-HSA-9018677	Biosynthesis of DHA-derived SPMs
R-HSA-9025106	Biosynthesis of DPAn-6 SPMs
R-HSA-9026290	Biosynthesis of DPAn-3-derived maresins
R-HSA-1430728	Metabolism
R-HSA-2142753	Arachidonate metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism
R-HSA-9018678	Biosynthesis of specialized proresolving mediators (SPMs)
R-HSA-9018683	Biosynthesis of DPA-derived SPMs
R-HSA-9025094	Biosynthesis of DPAn-3 SPMs

MSigDB gene sets: 188 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_LIPID_MODIFICATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_PLATELET_ACTIVATION, GOBP_PLATELET_ACTIVATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_SUPEROXIDE_METABOLIC_PROCESS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS

GO Biological Process (19): lipid metabolic process (GO:0006629), negative regulation of muscle cell apoptotic process (GO:0010656), arachidonate metabolic process (GO:0019369), lipoxygenase pathway (GO:0019372), fatty acid oxidation (GO:0019395), unsaturated fatty acid metabolic process (GO:0033559), lipid oxidation (GO:0034440), superoxide anion generation (GO:0042554), linoleic acid metabolic process (GO:0043651), hepoxilin biosynthetic process (GO:0051122), establishment of skin barrier (GO:0061436), negative regulation of platelet aggregation (GO:0090331), leukotriene A4 metabolic process (GO:1901751), lipoxin A4 biosynthetic process (GO:2001303), lipoxin B4 biosynthetic process (GO:2001306), long-chain fatty acid metabolic process (GO:0001676), fatty acid metabolic process (GO:0006631), icosanoid metabolic process (GO:0006690), long-chain fatty acid biosynthetic process (GO:0042759)

GO Molecular Function (11): arachidonate 12(S)-lipoxygenase activity (GO:0004052), iron ion binding (GO:0005506), linoleate 13S-lipoxygenase activity (GO:0016165), hepoxilin-epoxide hydrolase activity (GO:0047977), arachidonate 15-lipoxygenase activity (GO:0050473), 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), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), sarcolemma (GO:0042383), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Biosynthesis of specialized proresolving mediators (SPMs)	3
Arachidonate metabolism	2
Biosynthesis of DPA-derived SPMs	2
Metabolism of lipids	2
Biosynthesis of DPAn-3 SPMs	1
Fatty acid metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
long-chain fatty acid metabolic process	4
fatty acid metabolic process	4
long-chain fatty acid biosynthetic process	3
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	3
cellular anatomical structure	3
icosanoid metabolic process	2
unsaturated fatty acid metabolic process	2
olefinic compound metabolic process	2
unsaturated fatty acid biosynthetic process	2
lipoxin biosynthetic process	2
catalytic activity	2
primary metabolic process	1
muscle cell apoptotic process	1
regulation of muscle cell apoptotic process	1
negative regulation of apoptotic process	1
lipid oxidation	1
lipid modification	1
superoxide metabolic process	1
skin epidermis development	1
negative regulation of platelet activation	1
negative regulation of homotypic cell-cell adhesion	1
platelet aggregation	1
regulation of platelet aggregation	1
leukotriene metabolic process	1
epoxide metabolic process	1
fatty acid derivative metabolic process	1
lipoxin A4 metabolic process	1
lipoxin B4 metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
carboxylic acid metabolic process	1
fatty acid biosynthetic process	1
transition metal ion binding	1
epoxide hydrolase activity	1
binding	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen	1
dioxygenase activity	1
cation binding	1
oxidoreductase activity	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALOX12	ITGB4	P16144	748
ALOX12	ACACA	Q13085	723
ALOX12	UNC5B	Q8IZJ1	717
ALOX12	UNC5C	O95185	649
ALOX12	NTN1	O95631	648
ALOX12	UNC5A	Q6ZN44	639
ALOX12	DCC	P43146	638
ALOX12	ADORA2B	P29275	609
ALOX12	LOX	P28300	593
ALOX12	ALOX5AP	P20292	571
ALOX12	GPX4	P36969	562
ALOX12	NTN4	Q9HB63	555
ALOX12	NEO1	Q92859	548
ALOX12	DSCAM	O60469	547
ALOX12	PTGS1	P23219	544

IntAct

17 interactions, top by confidence:

A	B	Type	Score
ALOX12	KRT5	psi-mi:“MI:0915”(physical association)	0.540
KRT5	ALOX12	psi-mi:“MI:0915”(physical association)	0.540
KRT5	ALOX12	psi-mi:“MI:0403”(colocalization)	0.540
LMNA	ALOX12	psi-mi:“MI:0915”(physical association)	0.510
ALOX12	LMNA	psi-mi:“MI:0915”(physical association)	0.510
ALOX12	PLA2G2A	psi-mi:“MI:0915”(physical association)	0.400
ITGB4	ALOX12	psi-mi:“MI:0915”(physical association)	0.370
ALOX12	TRIB1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (16): ALOX12 (Co-crystal Structure), ALOX12 (Reconstituted Complex), ALOX12 (Affinity Capture-Western), ALOX12 (Reconstituted Complex), ALOX12 (Affinity Capture-Western), ALOX12 (Affinity Capture-Western), ALOX12 (Affinity Capture-Western), ALOX12 (Negative Genetic), ALOX12 (Affinity Capture-RNA), LMNA (Two-hybrid), ITGB4 (Two-hybrid), TRIB1 (Two-hybrid), KRT5 (Two-hybrid), LMNA (Affinity Capture-Western), KRT5 (Affinity Capture-Western)

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	67
Likely benign	9
Benign	32

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564377	GRCh37/hg19 17p13.3-12(chr17:525-11186432)x3	Pathogenic

SpliceAI

2549 predictions. Top by Δscore:

Variant	Effect	Δscore
17:6998836:GG:G	donor_gain	1.0000
17:6998837:GG:G	donor_gain	1.0000
17:6999294:C:A	acceptor_gain	1.0000
17:7000331:CCCAG:C	acceptor_loss	1.0000
17:7000332:CCAGA:C	acceptor_loss	1.0000
17:7000333:CA:C	acceptor_loss	1.0000
17:7000334:A:AC	acceptor_loss	1.0000
17:7000334:A:AG	acceptor_gain	1.0000
17:7000334:AGAAT:A	acceptor_gain	1.0000
17:7000335:G:GA	acceptor_gain	1.0000
17:7000335:GA:G	acceptor_gain	1.0000
17:7000335:GAA:G	acceptor_gain	1.0000
17:7000335:GAAT:G	acceptor_gain	1.0000
17:7000335:GAATG:G	acceptor_gain	1.0000
17:7000475:TCCAG:T	donor_gain	1.0000
17:7000478:AG:A	donor_gain	1.0000
17:7000479:GG:G	donor_gain	1.0000
17:7000480:G:GG	donor_gain	1.0000
17:7001807:TCAAG:T	donor_loss	1.0000
17:7001808:CAAG:C	donor_loss	1.0000
17:7001809:AAG:A	donor_loss	1.0000
17:7001811:GGTA:G	donor_loss	1.0000
17:7001812:G:T	donor_loss	1.0000
17:7001813:T:A	donor_loss	1.0000
17:7005341:AAGGT:A	donor_loss	1.0000
17:7005342:AGGTG:A	donor_loss	1.0000
17:7005343:GG:G	donor_loss	1.0000
17:7005941:T:TA	acceptor_gain	1.0000
17:7006026:AGG:A	donor_loss	1.0000
17:7006027:GGT:G	donor_loss	1.0000

AlphaMissense

4326 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7001682:G:C	K344N	0.974
17:7001682:G:T	K344N	0.974
17:6998791:T:C	F166L	0.968
17:6998793:C:A	F166L	0.968
17:6998793:C:G	F166L	0.968
17:6996919:T:C	F77L	0.964
17:6996921:C:A	F77L	0.964
17:6996921:C:G	F77L	0.964
17:7006559:T:A	W498R	0.963
17:7006559:T:C	W498R	0.963
17:6996916:T:A	W76R	0.957
17:6996916:T:C	W76R	0.957
17:7010409:A:C	S660R	0.957
17:7010411:T:A	S660R	0.957
17:7010411:T:G	S660R	0.957
17:6996970:T:C	F94L	0.952
17:6996972:C:A	F94L	0.952
17:6996972:C:G	F94L	0.952
17:7005864:A:C	S419R	0.952
17:7005866:C:A	S419R	0.952
17:7005866:C:G	S419R	0.952
17:7009806:T:C	F534L	0.951
17:7009808:C:A	F534L	0.951
17:7009808:C:G	F534L	0.951
17:7001686:T:A	W346R	0.948
17:7001686:T:C	W346R	0.948
17:7005295:C:A	N400K	0.948
17:7005295:C:G	N400K	0.948
17:7001756:A:T	E369V	0.945
17:7001780:G:C	R377P	0.944

dbSNP variants (sampled 300 via entrez): RS1000072006 (17:7003661 C>T), RS1000135530 (17:7002434 C>T), RS1000153685 (17:6995809 C>A), RS1000226884 (17:7006678 T>C), RS1000538858 (17:6999248 T>A), RS1000760335 (17:6994514 C>T), RS1001630105 (17:7005207 A>C,G), RS1002151692 (17:7004999 T>C,G), RS1002182737 (17:7004010 G>A), RS1002212758 (17:7000715 T>C), RS1002255621 (17:6997445 T>C), RS1002401837 (17:7003767 A>C,G), RS1002434768 (17:7006775 A>G), RS1002549174 (17:6995829 C>G,T), RS1002788675 (17:6994460 G>A,C)

Disease associations

OMIM: gene MIM:152391 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002395_240	Mean platelet volume	2.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3687 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

58 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 868,483 (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
CHEMBL1018	DIENESTROL	4	5,607
CHEMBL1129	TRIFLURIDINE	4	24,647
CHEMBL1200471	PYRITHIONE ZINC	4	24,834
CHEMBL1200596	CHLOROXINE	4	1,792
CHEMBL1200710	CLOMIPRAMINE HYDROCHLORIDE	4	5,044
CHEMBL1200970	ETHOPROPAZINE HYDROCHLORIDE	4	876
CHEMBL1201119	LIOTHYRONINE SODIUM	4	3,058
CHEMBL1201236	CARBIDOPA ANHYDROUS	4	25,180
CHEMBL1206	ETHOPROPAZINE	4	15,984
CHEMBL1208422	ROSE BENGAL FREE ACID	4	476
CHEMBL1274	NILUTAMIDE	4	64,154
CHEMBL12856	INAMRINONE	4	9,690
CHEMBL1382627	SULFADIAZINE, SILVER	4	561,177
CHEMBL1447476	BITHIONOLATE SODIUM	4	324
CHEMBL1454910	NITROXOLINE	4	1,860
CHEMBL1472989	BISOPROLOL FUMARATE	4	10,035
CHEMBL1590	PSEUDOEPHEDRINE	4	25,626
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL273575	NOMIFENSINE	4	7,327
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL313972	MASOPROCOL	4
CHEMBL34259	METHOTREXATE	4
CHEMBL421701	DITHIAZANINE IODIDE	4
CHEMBL496	HEXACHLOROPHENE	4
CHEMBL497	CLIOQUINOL	4
CHEMBL585	TRIAMTERENE	4
CHEMBL64894	GENTIAN VIOLET	4
CHEMBL679	EPINEPHRINE	4
CHEMBL786	TAMOXIFEN CITRATE	4
CHEMBL817	TOLAZAMIDE	4

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11078659	Efficacy,Toxicity	3	celecoxib	Colorectal Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11078659	ALOX12	3	2.50	1	celecoxib

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Lipoxygenases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
ML355	Inhibition	6.47	pIC50

ChEMBL bioactivities

865 potent at pChembl≥5 of 2847 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.66	Potency	2.2	nM	CHEMBL1270410
8.49	Potency	3.2	nM	CHEMBL1269896
8.49	Potency	3.2	nM	CHEMBL1331888
8.20	Potency	6.3	nM	CHEMBL1339179
8.10	Potency	7.9	nM	FLAVANONE
8.05	Potency	8.9	nM	CHEMBL1430985
7.60	Potency	25.1	nM	CHEMBL1578957
7.60	Potency	25.1	nM	CHEMBL3191182
7.50	Potency	31.6	nM	CHEMBL1308557
7.45	Potency	35.5	nM	CHEMBL1531156
7.40	Potency	39.8	nM	CHEMBL1543965
7.35	Potency	44.7	nM	CHEMBL254255
7.30	IC50	50	nM	CHEMBL4869861
7.25	Potency	56.2	nM	CHEMBL1549610
7.25	Potency	56.2	nM	CHEMBL1334710
7.15	Potency	70.8	nM	CHEMBL1601374
7.15	Potency	70.8	nM	CHEMBL1407135
7.10	Potency	79.4	nM	CHEMBL1447541
7.05	Potency	89.1	nM	CHEMBL1560296
7.00	IC50	100	nM	PHENIDONE
6.96	IC50	110	nM	NORDIHYDROGUAIARETIC ACID
6.90	Potency	125.9	nM	CHEMBL1499658
6.90	Potency	125.9	nM	CHEMBL1605701
6.85	Potency	141.3	nM	CHEMBL1324842
6.85	Potency	141.3	nM	CHEMBL1566706
6.82	IC50	150	nM	CHEMBL222808
6.80	IC50	160	nM	CHEMBL3113197
6.75	IC50	180	nM	CHEMBL3113193
6.75	IC50	180	nM	NORDIHYDROGUAIARETIC ACID
6.75	Potency	177.8	nM	CHEMBL1595951
6.75	Potency	177.8	nM	CHEMBL1365850
6.68	IC50	210	nM	MORACIN C
6.68	IC50	210	nM	CHEMBL238624
6.66	IC50	220	nM	CHEMBL3113198
6.65	Potency	223.9	nM	CHEMBL1566678
6.65	Potency	223.9	nM	CHEMBL1540789
6.65	Potency	223.9	nM	CHEMBL3197254
6.65	Potency	223.9	nM	CHEMBL1312186
6.62	IC50	240	nM	CHEMBL3113169
6.60	Potency	251.2	nM	CHEMBL3190293
6.60	Potency	251.2	nM	CHEMBL1988042
6.58	IC50	260	nM	CHEMBL3113192
6.58	IC50	260	nM	CHEMBL463805
6.55	IC50	280	nM	CHEMBL459185
6.55	Potency	281.8	nM	CHEMBL1569823
6.55	Potency	281.8	nM	CHEMBL1402668
6.55	Potency	281.8	nM	CHEMBL223453
6.55	Potency	281.8	nM	CHEMBL1979849
6.55	Potency	281.8	nM	CHEMBL1356623
6.55	Potency	281.8	nM	CHEMBL1333962

PubChem BioAssay actives

140 with measured affinity, of 582 total; 50 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
1-[(1S)-1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea	485949: Inhibition of human platelet N-terminal His6-tagged 12-lipoxygenase by UV-vis spectrometry	ic50	<0.0001	uM
N-benzo[e][1,3]benzothiazol-2-yl-4-[(2-hydroxy-3-methoxyphenyl)methylamino]benzenesulfonamide	1780088: Inhibition of wild type human N-terminal His-tagged 12-LOX using arachidonic acid as substrate by UV-Vis spectroscopy analysis	ic50	0.0500	uM
1-phenylpyrazolidin-3-one	3102: Compound was tested in vitro for inhibition of 12-LO human platelet	ic50	0.1000	uM
4-[4-(3,4-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol	611381: Inhibition of human platelet-type 12-lipoxygenase	ic50	0.1100	uM
4-[2-(3-carboxy-4-hydroxynaphthalen-1-yl)-2-oxoacetyl]-1-hydroxynaphthalene-2-carboxylic acid	301566: Inhibition of human 12-hLO	ic50	0.1500	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-(3-propan-2-ylphenyl)benzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.1600	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-(4-phenyl-1,3-thiazol-2-yl)benzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.1800	uM
5-(6-hydroxy-1-benzofuran-2-yl)-2-(3-methylbut-2-enyl)benzene-1,3-diol	1411787: Inhibition of human N-terminal His-tagged 12-LOX expressed in Escherichia coli(Rosetta) by rhodamine 123 dye-based fluorescence assay	ic50	0.2100	uM
2,6-dichloro-4-[1,2,2-tris(3,5-dichloro-4-hydroxyphenyl)ethyl]phenol	301566: Inhibition of human 12-hLO	ic50	0.2100	uM
N-(6-fluoro-1,3-benzothiazol-2-yl)-4-[(2-hydroxy-3-methoxyphenyl)methylamino]benzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.2200	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-(4-methyl-1,3-benzothiazol-2-yl)benzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.2400	uM
(4aS,6aS,12aR,12bS)-10-methoxy-4,4,6a,12b-tetramethyl-2,3,4a,5,6,12a-hexahydro-1H-benzo[a]xanthen-9-one	354433: Inhibition of His-tagged human platelet 12-lipoxygenase	ic50	0.2600	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-(6-methoxy-1,3-benzothiazol-2-yl)benzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.2600	uM
(4aS,6aS,12S,12aS,12bS)-10,12-dimethoxy-4,4,6a,12b-tetramethyl-1,2,3,4a,5,6,12,12a-octahydrobenzo[a]xanthen-9-ol	354433: Inhibition of His-tagged human platelet 12-lipoxygenase	ic50	0.2800	uM
3-(3-chlorophenyl)-6,7-dihydroxychromen-4-one	1800156: IC50 Assay from Article 10.1111/cbdd.12157: “In vitro study of isoflavones and isoflavans as potent inhibitors of human 12- and 15-lipoxygenases.”	ic50	0.2800	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-naphthalen-2-ylbenzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.3300	uM
N-(1,3-benzothiazol-2-yl)-4-[(2-hydroxy-3-methoxyphenyl)methylamino]benzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.3400	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-thiophen-2-ylbenzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.3500	uM
4-[(2S,3R)-4-(4,5-dihydroxy-2-nitrophenyl)-2,3-dimethylbutyl]-5-nitrobenzene-1,2-diol	3108: Inhibitory activity against human platelet 12-lipoxygenase (12-HLO)	ic50	0.3600	uM
4-chloro-5-[(2S,3R)-4-(2-chloro-4,5-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol	3108: Inhibitory activity against human platelet 12-lipoxygenase (12-HLO)	ic50	0.3600	uM
N-[(5-chloro-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]propanamide	611382: Inhibition of human platelet-type N-terminally His6-tagged 12-lipoxygenase assessed as conjugated diene product formation using arachidonic acid by UV-vis spectrophotometer analysis	ic50	0.3800	uM
N-(3-tert-butylphenyl)-4-[(2-hydroxy-3-methoxyphenyl)methylamino]benzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.3900	uM
(2E)-3-[3-bromo-5-[2,6-dibromo-4-[(2E)-3-[2-(3-bromo-4-hydroxyphenyl)ethylamino]-2-hydroxyimino-3-oxopropyl]phenoxy]-4-hydroxyphenyl]-N-[(E)-2-(3-bromo-4-hydroxyphenyl)ethenyl]-2-hydroxyiminopropanamide	241245: Inhibitory effect on human platelet 12-lipoxygenase	ic50	0.4000	uM
1-[[6-(4-fluorophenoxy)-2H-chromen-3-yl]methyl]-1-hydroxy-3-methylurea	3103: Inhibitory concentration against human platelet 12-lipoxygenase	ic50	0.4100	uM
2,3,4,5-tetrabromo-6-(3,5-dibromo-2-hydroxyphenoxy)phenol	241245: Inhibitory effect on human platelet 12-lipoxygenase	ic50	0.4100	uM
4-bromo-5-[(2S,3R)-4-(2-bromo-4,5-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol	3108: Inhibitory activity against human platelet 12-lipoxygenase (12-HLO)	ic50	0.4300	uM
N-[(5-bromo-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]acetamide	611382: Inhibition of human platelet-type N-terminally His6-tagged 12-lipoxygenase assessed as conjugated diene product formation using arachidonic acid by UV-vis spectrophotometer analysis	ic50	0.4300	uM
Quercetin	309798: Inhibition of 12-hLO	ic50	0.4400	uM
3-(4-chlorophenyl)-7,8-dihydroxychromen-4-one	309798: Inhibition of 12-hLO	ic50	0.4800	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-quinolin-3-ylbenzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.4800	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-phenylbenzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.5000	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-naphthalen-1-ylbenzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.5100	uM
N-(1,3-benzoxazol-2-yl)-4-[(2-hydroxy-3-methoxyphenyl)methylamino]benzenesulfonamide	1068691: Uncompetitive inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate assessed as 12-HPETE formation by Henri-Michaelis Menten equation analysis	ki	0.5300	uM
N-(1H-benzimidazol-2-yl)-4-[(2-hydroxy-3-methoxyphenyl)methylamino]benzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.5700	uM
1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methylbut-2-enyl)xanthen-9-one	301566: Inhibition of human 12-hLO	ic50	0.5800	uM
7,8-dihydroxy-3-[3-(trifluoromethyl)phenyl]chromen-4-one	309798: Inhibition of 12-hLO	ic50	0.6200	uM
1-hydroxy-1-[(6-phenoxy-2H-chromen-3-yl)methyl]urea	3105: Inhibitory concentration against human platelet 12-lipoxygenase	ic50	0.6400	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-isoquinolin-8-ylbenzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.7000	uM
2,3,4,5-tetrabromo-6-(2,4-dibromophenoxy)phenol	241245: Inhibitory effect on human platelet 12-lipoxygenase	ic50	0.7000	uM
tert-butyl 4-[3-[[4-[(2-hydroxy-3-methoxyphenyl)methylamino]phenyl]sulfonylamino]phenyl]piperidine-1-carboxylate	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	0.7600	uM
(4aS,6aS,12bS)-10-methoxy-4,4,6a,12b-tetramethyl-1,2,3,4a,5,6-hexahydrobenzo[a]xanthen-9-ol	354433: Inhibition of His-tagged human platelet 12-lipoxygenase	ic50	0.7800	uM
3-(3-chlorophenyl)-7,8-dihydroxychromen-4-one	309798: Inhibition of 12-hLO	ic50	0.7800	uM
N-[(8-hydroxy-5-nitroquinolin-7-yl)-thiophen-2-ylmethyl]propanamide	611382: Inhibition of human platelet-type N-terminally His6-tagged 12-lipoxygenase assessed as conjugated diene product formation using arachidonic acid by UV-vis spectrophotometer analysis	ic50	0.8000	uM
5,6,7-trihydroxy-2-phenylchromen-4-one	309798: Inhibition of 12-hLO	ic50	0.8600	uM
2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one	309798: Inhibition of 12-hLO	ic50	0.9500	uM
N-[(5-chloro-8-hydroxyquinolin-7-yl)-(furan-2-yl)methyl]propanamide	611382: Inhibition of human platelet-type N-terminally His6-tagged 12-lipoxygenase assessed as conjugated diene product formation using arachidonic acid by UV-vis spectrophotometer analysis	ic50	1.0000	uM
N-[(5-chloro-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]acetamide	611382: Inhibition of human platelet-type N-terminally His6-tagged 12-lipoxygenase assessed as conjugated diene product formation using arachidonic acid by UV-vis spectrophotometer analysis	ic50	1.0000	uM
(5Z,8Z,11Z,13E)-15-oxoicosa-5,8,11,13-tetraenoic acid	1179714: Inhibition of human platelet 12-lipoxygenase by UV-visible spectrophotometry	ic50	1.0000	uM
N-[3-(1H-indol-3-yl)propyl]-4-pentylbenzenesulfonamide	241369: Inhibitory concentration against human platelet-derived 12-lipoxygenase	ic50	1.0700	uM
4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-(3-piperidin-4-ylphenyl)benzenesulfonamide	1068709: Inhibition of N-terminal His6-tagged human platelet 12-LOX using arachidonic acid as substrate by UV-vis spectrophotometric analysis	ic50	1.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression	3
Masoprocol	decreases reaction, increases chemical synthesis, decreases activity	3
baicalein	decreases reaction, increases chemical synthesis, decreases activity	2
Resveratrol	decreases expression, decreases reaction, increases chemical synthesis, decreases activity, affects cotreatment	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
kaempferol	decreases reaction, increases chemical synthesis, decreases activity	1
deoxynivalenol	decreases expression	1
cerous chloride	affects cotreatment, decreases expression	1
lanthanum chloride	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
hydroquinone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
licochalcone B	increases expression	1
Bortezomib	increases response to substance	1
Aerosols	affects expression	1
Benzene	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Glucose	increases expression	1
Methotrexate	decreases expression	1
Nickel	decreases expression	1
Oxygen	increases expression	1
Pesticides	affects methylation	1
Platelet Activating Factor	increases expression	1
Polymyxin B	increases expression, increases reaction	1
Fenofibrate	increases expression	1
Quercetin	decreases reaction, increases chemical synthesis, decreases activity	1

ChEMBL screening assays

106 unique, capped per target: 96 binding, 9 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1066587	Binding	Inhibition of 12-lipoxygenase at 10 uM	Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2. — Bioorg Med Chem Lett
CHEMBL1613868	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of 12-hLO (12-human lipoxygenase) - Confirmatory and Counterscreen Data. (Class of assay: confirmatory) [Related pubchem assays: 2162 (confirmatory and SAR 12hLO data), 1452 (primary qHTS assay fo	PubChem BioAssay data set
CHEMBL4351295	ADMET	Inhibition of 12-lipoxygenase (unknown origin)	Novel Chemical Series of 5-Lipoxygenase-Activating Protein Inhibitors for Treatment of Coronary Artery Disease. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7ZN	HAP1 ALOX12 (-) 1	Cancer cell line	Male
CVCL_C7ZP	HAP1 ALOX12 (-) 2	Cancer cell line	Male
CVCL_DX23	HAP1 ALOX12 (-) ALOX15 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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