ALOX5AP

Summary

ALOX5AP (arachidonate 5-lipoxygenase activating protein, HGNC:436) is a protein-coding gene on chromosome 13q12.3, encoding Arachidonate 5-lipoxygenase-activating protein (P20292). Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase).

This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. Leukotrienes are arachidonic acid metabolites which have been implicated in various types of inflammatory responses, including asthma, arthritis and psoriasis. This protein localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 241 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 42 total — 4 pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001629

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:436
Approved symbol	ALOX5AP
Name	arachidonate 5-lipoxygenase activating protein
Location	13q12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLAP
Ensembl gene	ENSG00000132965
Ensembl biotype	protein_coding
OMIM	603700
Entrez	241

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000380490, ENST00000479597, ENST00000617770, ENST00000892335, ENST00000892336

RefSeq mRNA: 2 — MANE Select: NM_001629 NM_001204406, NM_001629

CCDS: CCDS73558, CCDS9337

Canonical transcript exons

ENST00000380490 — 5 exons

Exon	Start	End
ENSE00000906667	30744060	30744159
ENSE00000906668	30752052	30752122
ENSE00000906669	30755944	30756025
ENSE00001093601	30763944	30764426
ENSE00001485220	30735543	30735675

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 99.26.

FANTOM5 (CAGE): breadth broad, TPM avg 51.2140 / max 7670.4228, expressed in 786 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134629	49.6441	784
134630	1.4527	242
134625	0.1171	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.26	gold quality
trabecular bone tissue	UBERON:0002483	99.17	gold quality
bone marrow	UBERON:0002371	98.87	gold quality
right lung	UBERON:0002167	98.43	gold quality
granulocyte	CL:0000094	98.42	gold quality
leukocyte	CL:0000738	97.53	gold quality
bone marrow cell	CL:0002092	97.41	gold quality
mononuclear cell	CL:0000842	97.40	gold quality
monocyte	CL:0000576	97.38	gold quality
upper lobe of left lung	UBERON:0008952	97.32	gold quality
spleen	UBERON:0002106	97.05	gold quality
upper lobe of lung	UBERON:0008948	97.05	gold quality
lower lobe of lung	UBERON:0008949	95.67	gold quality
periodontal ligament	UBERON:0008266	95.37	gold quality
vermiform appendix	UBERON:0001154	95.14	gold quality
adult organism	UBERON:0007023	94.42	gold quality
gall bladder	UBERON:0002110	93.98	gold quality
lung	UBERON:0002048	93.74	gold quality
lymph node	UBERON:0000029	93.58	gold quality
descending thoracic aorta	UBERON:0002345	93.25	gold quality
left coronary artery	UBERON:0001626	91.83	gold quality
omental fat pad	UBERON:0010414	91.72	gold quality
peritoneum	UBERON:0002358	91.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.55	gold quality
right adrenal gland cortex	UBERON:0035827	91.54	gold quality
right coronary artery	UBERON:0001625	91.10	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.09	gold quality
thoracic aorta	UBERON:0001515	90.74	gold quality
left adrenal gland	UBERON:0001234	90.68	gold quality
ascending aorta	UBERON:0001496	90.35	gold quality

Single-cell (SCXA)

Detected in 38 experiment(s), a significant marker in 36.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	3746.80
E-MTAB-8495	yes	3427.05
E-CURD-126	yes	2865.83
E-MTAB-9435	yes	2827.94
E-MTAB-8498	yes	2286.08
E-GEOD-134144	yes	1811.14
E-GEOD-139324	yes	1801.41
E-GEOD-84465	yes	1790.47
E-MTAB-8322	yes	1613.77
E-MTAB-10432	yes	1529.45
E-HCAD-10	yes	1350.88
E-MTAB-8142	yes	85.48
E-HCAD-1	yes	83.31
E-HCAD-4	yes	73.57
E-CURD-88	yes	48.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPD, CEBPG, E2F1, EGR1, HIF1A, IRF6, NFKB1, NFKB, RELA

miRNA regulators (miRDB)

22 targeting ALOX5AP, 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-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-135A-2-3P	98.40	66.74	442
HSA-MIR-135B-3P	98.40	67.35	426
HSA-MIR-335-5P	97.10	68.12	1022
HSA-MIR-331-5P	96.59	67.94	705
HSA-MIR-5681B	94.82	69.30	514

Literature-anchored findings (GeneRIF, showing 40)

• FLAP gene is transactivated by members of the C/EBP family of transcription factors in inflammatory cells and that these factors play an important role in FLAP gene induction by TNFalpha (PMID:12571239)
• LOX5 and FLAP pathway in monocytes and microglia yields products toxic toward neurons (neuroblastoma cell line) (PMID:12629151)
• We conclude that variants of ALOX5AP are involved in the pathogenesis of both myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall. (PMID:14770184)
• Both the eicosanoids PGE(2) and LTB(4) are important cofactors in regulating FLAP expression; the inhibition of PGE(2) down-regulates FLAP gene expression. (PMID:15593193)
• role for ALOX5AP variant in stroke patients (PMID:15640973)
• Variants in the ALOX5AP gene but not the PDE4D gene are associated with risk for stroke in individuals from central Europe (PMID:15731479)
• ALOX5AP (encoding 5-lipoxygenase-activating protein) associated with myocardial infarction and stroke (PMID:15861005)
• FLAP is present as a monomer and a homodimer in human polymorphonuclear cells; leukotriene biosynthesis in intact cells not only requires the presence of FLAP but its further organization into a FLAP homodimer. (PMID:16144515)
• No evidence for association of specific Icelandic ALOX5P gene variants/at-risk haplotypes tested with risk of incident myocardial infarction nor ischemic stroke in this prospective, non-Icelandic study. (PMID:16778124)
• No association of polymorphisms in the gene encoding 5-lipoxygenase-activating protein and myocardial infarction in a large central European population. (PMID:17304054)
• Study reports significant association of variants of ALOX5AP with ischemic stroke and ischemic stroke subtypes among whites; no significant association was identified among blacks. (PMID:17387518)
• the role of variants of the gene encoding arachidonate 5-lipoxygenase-activating protein (ALOX5AP) as possible susceptibility factors for coronary artery disease and myocardial infarction in patients with or without angiographically proven CAD (PMID:17505527)
• x-ray crystal structures of FLAP in complex with two leukotriene biosynthesis inhibitors at 4.0 and 4.2 angstrom resolution, respectively; structures show that inhibitors bind in membrane-embedded pockets of FLAP (PMID:17600184)
• a significant correlation of FLAP gene promoter 17A allele carriers with higher plasma high-sensitivity C-reactive protein levels in patients with coronary artery disease. (PMID:17627106)
• This study did not confirm the association between ALOX5AP HapA haplotype and ICVD, but a non-significant risk was observed in the Large Artery Atherosclerosis subtype. (PMID:17655870)
• Diffraction-quality crystals of FLAP in complex with leukotriene-synthesis inhibitor MK-591 and with an iodinated analogue of MK-591 have been grown using the sitting-drop vapor-diffusion method (PMID:18084092)
• Genetic variation in leukotriene pathway members and their receptors confer an increased risk of ischemic stroke in 2 independent populations (PMID:18323512)
• findings do not support a link between common allelic variation in or near ALOX5 or ALOX5AP and the risk of coronary artery disease (PMID:18369664)
• These data provide evidence for the role of SNPs spanning the ALOX5AP and LTA4H genes in asthma and atopy susceptibility (PMID:18547289)
• genetic variation in the ALOX5AP gene contributes to CHD risk in patients with familial hypercholesterolemia (PMID:18775537)
• There was a significant interaction between the ALOX5AP -4900 A>G polymorphism and dietary linoleic acid intake. (PMID:18843019)
• PlGF-mediated increased FLAP mRNA expression occurred via activation of phosphoinositide-3 (PI-3) kinase, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and hypoxia inducible factor-1alpha (HIF-1alpha). (PMID:18945963)
• meta-analysis of all studies with ALOX5AP genotyping showed significant heterogeneity among studies and a nonsignificant association between the HapA haplotype and stroke risk [review] (PMID:19126581)
• LTC(4)S interacts in vitro with both FLAP and 5-LO and that these interactions involve distinct parts of LTC(4)S. (PMID:19233132)
• Results suggest that ALOX5AP, IRAK1, and FABP2 are susceptibility loci for CKD among Japanese individuals with type 2 diabetes mellitus. (PMID:19288030)
• Variants in the ALOX5AP gene are associated with the presence of xanthomas in familial hypercholesterolemia patients. This result supports our hypothesis that inflammation is a pathogenetic factor of xanthomas. (PMID:19361804)
• MTHFR C677T, ALOX5AP T2354A and NOTCH3 C381T were significant combinational contributors to thrombotic stroke. (PMID:19373490)
• we found no evidence of association between PDE4D and ALOX5AP genes and the risk of IS in a genetically homogenous population from Sardinia. (PMID:19417766)
• Suggests a significant but modest contribution of the ALOX5AP gene variants to the susceptibility of premature coronary artery disease in an US Midwestern population of European-American ancestry. (PMID:19596330)
• The polymorphism of SG13S114A/T in ALOX5AP is not related with atherosclerotic cerebral infarction. (PMID:20014490)
• Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations. (PMID:20067482)
• no association between gene polymorphism and bronchial asthma in a Spanish population (PMID:20128419)
• hypoxia-mediated 5-lipoxygenase activating protein expression is regulated by hypoxia-response elements and NF-kappaB site in its promoter, and negatively regulated by miR-135a and miR-199a-5p (PMID:20194722)
• The ALOX5AP SG13S114 variant is an independent risk factor for ischemic stroke in the Iberian population and is associated with ALOX5AP expression levels (PMID:20357438)
• The polymorphism of SG13S114 A/T in the ALOX5AP gene may be associated with the instability of atherosclerosis. (PMID:20376802)
• LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma. (PMID:20810156)
• These results suggested that the genetic variants in ALOX5AP might modulate the risk of stroke in Eastern Chinese Han population. (PMID:21153769)
• Data show that the HapB haplotype and rs1722842 polymorphism in ALOX5AP gene were associated with coronary heart disease, and the HapA haplotype was associated with risk of MI. (PMID:21199733)
• Polymorphisms of the 5-lipo-oxygenase-activating protein may be associated with chronic spontaneous urticaria. (PMID:21227888)
• No statistically significant associations were found between acute stroke and the ALOX5AP gene polymorphisms examined (PMID:21675249)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	alox5ap	ENSDARG00000054755
mus_musculus	Alox5ap	ENSMUSG00000060063
rattus_norvegicus	Alox5ap	ENSRNOG00000000907

Paralogs (3): MGST2 (ENSG00000085871), MGST3 (ENSG00000143198), LTC4S (ENSG00000213316)

Protein

Protein identifiers

Arachidonate 5-lipoxygenase-activating protein — P20292 (reviewed: P20292)

Alternative names: FLAP, MK-886-binding protein

All UniProt accessions (2): A0A087WW23, P20292

UniProt curated annotations — full annotation on UniProt →

Function. Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes.

Subunit / interactions. Homotrimer. Interacts with LTC4S and ALOX5.

Subcellular location. Nucleus membrane. Endoplasmic reticulum membrane.

Disease relevance. Ischemic stroke (ISCHSTR) [MIM:601367] A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Disease susceptibility is associated with variants affecting the gene represented in this entry. Genetic variations in ALOX5AP may be associated with susceptibility to myocardial infarction. Involvement in myocardial infarction is however unclear: according to some authors, a 4-SNP haplotype in ALOX5AP confers risk of myocardial infarction, while according to other ALOX5AP is not implicated in this condition.

Domain organisation. The C-terminal part after residue 140 is mostly unstructured.

Similarity. Belongs to the MAPEG family.

RefSeq proteins (2): NP_001191335, NP_001620* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001129	Membr-assoc_MAPEG	Family
IPR001446	5_LipOase_AP	Family
IPR018295	FLAP/GST2/LTC4S_CS	Conserved_site
IPR023352	MAPEG-like_dom_sf	Homologous_superfamily
IPR050997	MAPEG	Family

Pfam: PF01124

UniProt features (27 total): mutagenesis site 9, helix 6, topological domain 5, transmembrane region 4, chain 1, sequence conflict 1, intramembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6VGC	X-RAY DIFFRACTION	2.37
6VGI	X-RAY DIFFRACTION	2.61
2Q7R	X-RAY DIFFRACTION	4
2Q7M	X-RAY DIFFRACTION	4.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20292-F1	89.29	0.63

Functional residue map

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

Mutagenesis-validated functional residues (9):

Position	Phenotype
20	increased affinity for the inhibitor mk-591.
27	strongly decreased affinity for the inhibitor mk-591.
30	strongly decreased affinity for the inhibitor mk-591.
62	decreased affinity for the inhibitor mk-591.
66	strongly decreased affinity for the inhibitor mk-591.
112	strongly decreased affinity for the inhibitor mk-591.
113	increased affinity for the inhibitor mk-591.
116	strongly increased affinity for the inhibitor mk-591.
123	decreased affinity for the inhibitor mk-591.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-2142688	Synthesis of 5-eicosatetraenoic acids
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-2142700	Biosynthesis of Lipoxins (LX)
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)

MSigDB gene sets: 331 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, MCLACHLAN_DENTAL_CARIES_UP, GOBP_INFLAMMATORY_RESPONSE, MODULE_45, MODULE_16, GOBP_LEUKOTRIENE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, GOBP_RESPONSE_TO_METAL_ION, MODULE_118, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_TRIMERIZATION, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, MARTINEZ_RB1_TARGETS_DN

GO Biological Process (7): leukotriene production involved in inflammatory response (GO:0002540), leukotriene biosynthetic process (GO:0019370), protein homotrimerization (GO:0070207), cellular response to calcium ion (GO:0071277), leukotriene metabolic process (GO:0006691), carboxylic acid biosynthetic process (GO:0046394), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (6): glutathione transferase activity (GO:0004364), leukotriene-C4 synthase activity (GO:0004464), glutathione peroxidase activity (GO:0004602), enzyme activator activity (GO:0008047), arachidonate binding (GO:0050544), protein binding (GO:0005515)

GO Cellular Component (6): nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), nuclear membrane (GO:0031965), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Arachidonate metabolism	2
Metabolism of lipids	2
Biosynthesis of specialized proresolving mediators (SPMs)	1
Fatty acid metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleus	2
endomembrane system	2
intracellular membrane-bounded organelle	2
organelle membrane	2
arachidonate metabolite production involved in inflammatory response	1
leukotriene metabolic process	1
icosanoid biosynthetic process	1
protein homooligomerization	1
protein trimerization	1
response to calcium ion	1
cellular response to metal ion	1
icosanoid metabolic process	1
carboxylic acid metabolic process	1
small molecule biosynthetic process	1
cellular detoxification	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
carbon-sulfur lyase activity	1
peroxidase activity	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
icosanoid binding	1
icosatetraenoic acid binding	1
binding	1
organelle envelope	1
cytoplasm	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
nuclear envelope	1

Protein interactions and networks

STRING

1630 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALOX5AP	ALOX5	P09917	991
ALOX5AP	LTA4H	P09960	950
ALOX5AP	MGST1	P10620	894
ALOX5AP	MGST3	O14880	848
ALOX5AP	PTGES	O14684	847
ALOX5AP	COTL1	Q14019	787
ALOX5AP	CYSLTR1	Q9Y271	784
ALOX5AP	CYSLTR2	Q9NS75	741
ALOX5AP	PLA2G4A	P47712	741
ALOX5AP	LTB4R	Q15722	647
ALOX5AP	ACE	P12821	635
ALOX5AP	PRKCH	P24723	628
ALOX5AP	ALOX15	P16050	611
ALOX5AP	EPHX2	P34913	610
ALOX5AP	NINJ2	Q9NZG7	586

IntAct

25 interactions, top by confidence:

A	B	Type	Score
ALOX5AP	OPRM1	psi-mi:“MI:0915”(physical association)	0.560
ALOX5AP	NAPB	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	ALOX5AP	psi-mi:“MI:0915”(physical association)	0.560
ALOX5AP		psi-mi:“MI:0915”(physical association)	0.560
GPR42	ALOX5AP	psi-mi:“MI:0915”(physical association)	0.560
ALOX5AP	AQP6	psi-mi:“MI:0915”(physical association)	0.560
FFAR2	ALOX5AP	psi-mi:“MI:0915”(physical association)	0.560
ALOX5AP	FRA10AC1	psi-mi:“MI:0915”(physical association)	0.400
ALOX5AP	ALOX5AP	psi-mi:“MI:0915”(physical association)	0.400
CLIC1	ALOX5AP	psi-mi:“MI:0915”(physical association)	0.370
ALOX5AP	OPRM1	psi-mi:“MI:0915”(physical association)	0.000
NAPB	ALOX5AP	psi-mi:“MI:0915”(physical association)	0.000
TMEM120B	ALOX5AP	psi-mi:“MI:0915”(physical association)	0.000
	ALOX5AP	psi-mi:“MI:0915”(physical association)	0.000
ALOX5AP	GPR42	psi-mi:“MI:0915”(physical association)	0.000
ALOX5AP	AQP6	psi-mi:“MI:0915”(physical association)	0.000
ALOX5AP	FFAR2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): ALOX5AP (Co-localization), ALOX5AP (Co-localization), FRA10AC1 (Affinity Capture-MS), ALOX5AP (Two-hybrid), ALOX5AP (Two-hybrid), ALOX5AP (Two-hybrid), ALOX5AP (Two-hybrid), ALOX5AP (Two-hybrid), SLC29A2 (Two-hybrid), TMEM120B (Two-hybrid), ALOX5AP (Reconstituted Complex), ALOX5 (Reconstituted Complex), ALOX5AP (Reconstituted Complex), ALOX5AP (Co-crystal Structure), CLIC1 (Two-hybrid)

ESM2 similar proteins: A5PN43, A6ZIQ8, C7T2J9, E1BY51, O19133, O43462, O80594, P20291, P20292, P30353, P30354, P30355, P30356, P30357, P30358, P35575, P51811, Q01685, Q148F2, Q15035, Q15629, Q19KA1, Q1PET6, Q29RU6, Q2PG08, Q49LS5, Q5F383, Q5FVJ3, Q5GH61, Q5R7Z3, Q5RAC8, Q5VWC8, Q5XI41, Q5ZKY0, Q6DED0, Q6YWS8, Q7X6P3, Q8CHX6, Q8TCT6, Q8VZB2

Diamond homologs: A2RST1, A6XA80, O14880, P20291, P20292, P30353, P30354, P30355, P30356, P30357, P30358, P73795, Q148F2, Q16873, Q2KJG4, Q2NKS0, Q2PG08, Q3T100, Q60860, Q925U2, Q99735, Q9CPU4, Q54GA9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	23
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1180526	GRCh37/hg19 13q12.3-13.2(chr13:28925153-34061696)x1	Pathogenic
148858	GRCh38/hg38 13q12.3-13.3(chr13:29073320-36556014)x1	Pathogenic
57637	GRCh38/hg38 13q12.3-13.1(chr13:29654134-32858245)x1	Pathogenic
59861	GRCh38/hg38 13q12.11-12.3(chr13:18958091-31090460)x3	Pathogenic

SpliceAI

862 predictions. Top by Δscore:

Variant	Effect	Δscore
13:30735671:GAATG:G	donor_gain	1.0000
13:30735672:AATGG:A	donor_loss	1.0000
13:30735673:ATGG:A	donor_loss	1.0000
13:30735674:TGGTA:T	donor_loss	1.0000
13:30735675:GGT:G	donor_loss	1.0000
13:30735676:G:GG	donor_gain	1.0000
13:30735676:GT:G	donor_loss	1.0000
13:30735677:T:G	donor_loss	1.0000
13:30735682:A:T	donor_gain	1.0000
13:30744160:G:GG	donor_gain	1.0000
13:30763942:A:AG	acceptor_gain	1.0000
13:30763943:G:GA	acceptor_gain	1.0000
13:30763943:GC:G	acceptor_gain	1.0000
13:30763943:GCACC:G	acceptor_gain	1.0000
13:30735674:TG:T	donor_gain	0.9900
13:30735675:GG:G	donor_gain	0.9900
13:30748510:C:G	donor_gain	0.9900
13:30755942:A:AG	acceptor_gain	0.9900
13:30755943:G:GG	acceptor_gain	0.9900
13:30763938:TTCCA:T	acceptor_loss	0.9900
13:30763939:TCCAG:T	acceptor_loss	0.9900
13:30763940:CCAG:C	acceptor_loss	0.9900
13:30763941:CAGC:C	acceptor_loss	0.9900
13:30763942:AGC:A	acceptor_loss	0.9900
13:30763943:GCA:G	acceptor_gain	0.9900
13:30763943:GCAC:G	acceptor_gain	0.9900
13:30735672:AATG:A	donor_gain	0.9800
13:30735673:ATG:A	donor_gain	0.9800
13:30744156:CCAAG:C	donor_loss	0.9800
13:30744159:AGTG:A	donor_loss	0.9800

AlphaMissense

1058 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:30735660:A:C	S19R	0.999
13:30735662:C:A	S19R	0.999
13:30735662:C:G	S19R	0.999
13:30752095:T:A	W72R	0.999
13:30752095:T:C	W72R	0.999
13:30744156:C:A	A56D	0.998
13:30752080:T:C	F67L	0.998
13:30752082:C:A	F67L	0.998
13:30752082:C:G	F67L	0.998
13:30755961:G:A	G87R	0.998
13:30755961:G:C	G87R	0.998
13:30755962:G:A	G87E	0.998
13:30755983:G:C	R94T	0.998
13:30755983:G:T	R94M	0.998
13:30752101:G:C	A74P	0.997
13:30752102:C:A	A74E	0.997
13:30752104:G:A	G75R	0.997
13:30752104:G:C	G75R	0.997
13:30752104:G:T	G75W	0.997
13:30755950:C:A	A83D	0.997
13:30755984:G:C	R94S	0.997
13:30755984:G:T	R94S	0.997
13:30752105:G:A	G75E	0.996
13:30755959:C:A	A86D	0.996
13:30755991:T:C	Y97H	0.996
13:30755994:T:C	F98L	0.996
13:30755996:T:A	F98L	0.996
13:30755996:T:G	F98L	0.996
13:30755970:T:G	Y90D	0.995
13:30763952:G:A	G111D	0.995

dbSNP variants (sampled 300 via entrez): RS1000006854 (13:30729860 G>C,T), RS1000150654 (13:30746109 G>A,C,T), RS1000151151 (13:30714637 A>G), RS1000152628 (13:30735107 C>T), RS1000161046 (13:30734947 A>G), RS1000223991 (13:30750221 C>T), RS1000316661 (13:30740795 G>A), RS1000474158 (13:30746634 G>A), RS1000507273 (13:30729569 A>C), RS1000778845 (13:30757973 G>A,T), RS1000817854 (13:30719617 T>C), RS1000831325 (13:30740156 T>A), RS1000834213 (13:30730442 G>A,C), RS1000838643 (13:30725597 G>A), RS1000938687 (13:30763471 C>T)

Disease associations

OMIM: gene MIM:603700 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0001297	Stroke
HP:0001426	Non-Mendelian inheritance
HP:0003581	Adult onset

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002059_5	Non-word repetition	7.000000e-06
GCST002176_1	Adverse response to chemotherapy in breast cancer (alopecia) (cyclophosphamide+epirubicin+/-5FU)	1.000000e-06
GCST007325_206	General risk tolerance (MTAG)	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005299	non-word reading
EFO:0008579	risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111402 (PROTEIN COMPLEX), CHEMBL4550 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 180,574 (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
CHEMBL112	ACETAMINOPHEN	4	157,242
CHEMBL93	ZILEUTON	4	21,372
CHEMBL1922660	FIBOFLAPON	3	303
CHEMBL16596	QUIFLAPON	2	694
CHEMBL300982	LICOFELONE	2	963

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4769060	ALOX5AP		0.00	0

Binding affinities (BindingDB)

1840 measured of 1970 human assays (1970 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
cis-(1R,2S)-2-[1-[[2-fluoro-4-(4-fluoropiperidin-1-yl)phenyl]methyl]-6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.34 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
6-[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-2-benzylpyrimidin-4-amine	KI	0.4 nM	US-9073876: Flap modulators
5-[4-(2-cyclohexylsulfonyl-3-pyridinyl)-2-fluorophenyl]pyrazin-2-amine	KI	0.4 nM	US-9884878: FLAP modulators
cis-(1R,2S)-2-[6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]-1-[[4-(4-fluoropiperidin-1-yl)phenyl]methyl]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.42 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
cis-(1R,2S)-2-[6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]-1-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.47 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
2-[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]quinazolin-4-amine	KI	0.5 nM	US-9073876: Flap modulators
trans-(1S,2S)-2-[1-[(4-bromo-2,6-difluorophenyl)methyl]-6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.52 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
5-[4-[2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]phenyl]-2-fluorophenyl]pyrazin-2-amine	KI	0.6 nM	US-9884878: FLAP modulators
5-[4-(2-cyclopentylsulfonyl-3-pyridinyl)-2-fluorophenyl]pyrazin-2-amine	KI	0.6 nM	US-9884878: FLAP modulators
cis-(1S,2R)-2-[1-[(4-bromo-2,6-difluorophenyl)methyl]-6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.61 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
2-[[1-[(4-bromophenyl)methyl]-6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]methyl]-2-ethylbutanoic acid	KI	0.64 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
cis-(1R,2S)-2-[1-[[2,6-difluoro-4-[4-(trifluoromethyl)phenyl]phenyl]methyl]-6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.66 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
2-[6-(2-aminopyrimidin-5-yl)-5-fluoro-3-pyridinyl]-N-tert-butylbenzenesulfonamide	KI	0.7 nM	US-9884878: FLAP modulators
5-[2-fluoro-4-(2-propan-2-ylsulfonyl-3-pyridinyl)phenyl]-1H-pyrrolo[2,3-b]pyridine	KI	0.7 nM	US-9884878: FLAP modulators
cis-(1S,2R)-2-[1-[(4-bromo-2-fluorophenyl)methyl]-6-[(5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.74 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
CHEMBL2031657	IC50	0.8 nM
cis-(1S,2R)-2-[1-[[2-fluoro-4-(4-fluoropiperidin-1-yl)phenyl]methyl]-6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.82 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
cis-(1S,2R)-2-[1-[[2,6-difluoro-4-(4-fluoropiperidin-1-yl)phenyl]methyl]-6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.84 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
4-[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-N,6-dimethylpyrimidin-2-amine	KI	0.9 nM	US-9073876: Flap modulators
2-[5-(2-aminopyrimidin-5-yl)-1-tert-butylbenzimidazol-2-yl]-N-pyridin-4-ylbenzamide	IC50	0.91 nM	US-8829200: Benzimidazole inhibitors of leukotriene production
(1R)-2-[6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]-1-[[2-fluoro-4-[4-(trifluoromethyl)piperidin-1-yl]phenyl]methyl]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.95 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
cis-(1R,2S)-2-[1-[[4-(3,3-difluoropyrrolidin-1-yl)-2-fluorophenyl]methyl]-6-[(5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	KI	0.96 nM	US-9695149: 1,2,6-substituted benzimidazoles as flap modulators
5-[4-cyclobutyl-2-fluoro-3-(4-phenylpyrimidin-2-yl)oxyphenyl]pyrazin-2-amine	KI	1 nM	US-9073876: Flap modulators
5-[4-cyclobutyl-2-fluoro-3-(4-thiophen-2-ylpyrimidin-2-yl)oxyphenyl]pyrazin-2-amine	KI	1 nM	US-9073876: Flap modulators
6-[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-2-methoxypyrimidin-4-amine	KI	1 nM	US-9073876: Flap modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-tert-butylbenzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-cyclohexylbenzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-(1,1,1-trifluoropropan-2-yl)benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)benzenesulfonamide	KI	1 nM	US-9079866: Flap modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-[(1R)-2,3-dihydro-1H-inden-1-yl]benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-phenylbenzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N,N-diethylbenzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
5-[4-[2-(3,3-difluoropiperidin-1-yl)sulfonylphenyl]-2-fluorophenyl]pyrazin-2-amine	KI	1 nM	US-9884878: FLAP modulators
1-[2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]phenyl]sulfonyl-4-(trifluoromethyl)piperidin-4-ol	KI	1 nM	US-9884878: FLAP modulators
[1-[2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]phenyl]sulfonylpiperidin-4-yl]methanol	KI	1 nM	US-9884878: FLAP modulators
2-[1-[2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]phenyl]sulfonylpiperidin-4-yl]ethanol	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-[(1S,2S)-1,3-dihydroxy-1-phenylpropan-2-yl]benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-[(1R)-2-hydroxy-1-phenylethyl]benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-[(1S,2S)-1-hydroxy-1-phenylpropan-2-yl]benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-(cyclopropylmethyl)benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-(1-hydroxy-2-methylpropan-2-yl)benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-[(1S,2S)-2-hydroxycyclohexyl]benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-[(1R,2S)-2-(hydroxymethyl)cyclohexyl]benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
5-[2-fluoro-4-[2-(1,4,6,7-tetrahydropyrazolo[4,5-c]pyridin-5-ylsulfonyl)phenyl]phenyl]pyrazin-2-amine	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-(6-hydroxyhexyl)benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
N-(4-aminocyclohexyl)-2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-cyclohexyl-N-(2-hydroxyethyl)benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-cyclopropyl-N-(oxan-4-yl)benzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators
2-[4-(5-aminopyrazin-2-yl)-3-fluorophenyl]-N-(2-hydroxyethyl)-N-propan-2-ylbenzenesulfonamide	KI	1 nM	US-9884878: FLAP modulators

ChEMBL bioactivities

4010 potent at pChembl≥5 of 4031 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL1922653
9.47	Ki	0.34	nM	CHEMBL3667000
9.40	Ki	0.4	nM	CHEMBL3704300
9.40	Ki	0.4	nM	CHEMBL3700843
9.40	IC50	0.4	nM	CHEMBL1922655
9.40	IC50	0.4	nM	CHEMBL1922656
9.40	IC50	0.4	nM	CHEMBL1922657
9.40	IC50	0.4	nM	CHEMBL1922663
9.38	Ki	0.42	nM	CHEMBL3667001
9.33	Ki	0.47	nM	CHEMBL3666967
9.30	Ki	0.5	nM	CHEMBL3659304
9.30	IC50	0.5	nM	CHEMBL5283430
9.30	IC50	0.5	nM	QUIFLAPON SODIUM
9.30	IC50	0.5	nM	CHEMBL557527
9.30	IC50	0.5	nM	CHEMBL1922532
9.30	IC50	0.5	nM	CHEMBL1922642
9.30	IC50	0.5	nM	CHEMBL1922658
9.30	IC50	0.5	nM	CHEMBL1922659
9.30	IC50	0.5	nM	CHEMBL1922662
9.30	IC50	0.5	nM	CHEMBL1922665
9.28	Ki	0.52	nM	CHEMBL3666952
9.22	Ki	0.6	nM	CHEMBL3697283
9.22	Ki	0.6	nM	CHEMBL3700845
9.22	IC50	0.6	nM	CHEMBL1922643
9.22	IC50	0.6	nM	CHEMBL1922645
9.22	IC50	0.6	nM	CHEMBL1922661
9.22	IC50	0.6	nM	CHEMBL1922664
9.22	IC50	0.6	nM	CHEMBL1922666
9.22	IC50	0.6	nM	CHEMBL1229205
9.21	Ki	0.61	nM	CHEMBL3666951
9.19	Ki	0.64	nM	CHEMBL3666964
9.18	Ki	0.66	nM	CHEMBL3666965
9.15	Ki	0.7	nM	CHEMBL3697342
9.15	Ki	0.7	nM	CHEMBL3700861
9.15	IC50	0.7	nM	CHEMBL5269712
9.15	IC50	0.7	nM	CHEMBL5274418
9.15	IC50	0.7	nM	CHEMBL1922524
9.15	IC50	0.7	nM	CHEMBL1922525
9.15	IC50	0.7	nM	CHEMBL1922646
9.15	IC50	0.7	nM	CHEMBL1922647
9.15	IC50	0.7	nM	FIBOFLAPON
9.13	Ki	0.74	nM	CHEMBL3662244
9.10	IC50	0.8	nM	CHEMBL2031657
9.10	IC50	0.8	nM	CHEMBL1922523
9.10	IC50	0.8	nM	CHEMBL1922654
9.09	Ki	0.82	nM	CHEMBL3666999
9.08	Ki	0.84	nM	CHEMBL3666998
9.05	Ki	0.9	nM	CHEMBL3659301
9.04	IC50	0.91	nM	CHEMBL3681322
9.02	Ki	0.96	nM	CHEMBL3666989

PubChem BioAssay actives

781 with measured affinity, of 1202 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
3-[3-tert-butylsulfanyl-1-[[4-(6-methoxy-2-pyridinyl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0003	uM
3-[3-tert-butylsulfanyl-1-[[4-(2-ethoxy-1,3-thiazol-4-yl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0004	uM
3-[3-tert-butylsulfanyl-5-[(5-methyl-2-pyridinyl)methoxy]-1-[[4-[4-(trifluoromethyl)-2-pyridinyl]phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0004	uM
3-[3-tert-butylsulfanyl-5-[(5-methyl-2-pyridinyl)methoxy]-1-[[4-[6-(trifluoromethyl)-3-pyridinyl]phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0004	uM
3-[3-tert-butylsulfanyl-1-[[4-(5-fluoro-2-pyridinyl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0004	uM
3-[3-tert-butylsulfanyl-5-[(5-methyl-2-pyridinyl)methoxy]-1-[[4-[6-(trifluoromethyl)-2-pyridinyl]phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0005	uM
3-[3-tert-butylsulfanyl-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]-5-(pyridin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0005	uM
sodium 3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0005	uM
2-[6-[6-[2-[4-(2-aminopyrimidin-5-yl)phenyl]-3-methylbutan-2-yl]-3-pyridinyl]pyridazin-3-yl]propan-2-ol	1940807: Inhibition of FLAP in human Leucocyte membrane incubated for 20 mins by radioactivity based gamma-scintillation counter assay	ic50	0.0005	uM
3-[3-tert-butylsulfanyl-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0005	uM
3-[3-tert-butylsulfanyl-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]-5-[(6-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0005	uM
3-[3-tert-butylsulfanyl-5-[(5-methyl-2-pyridinyl)methoxy]-1-[[4-[5-(trifluoromethyl)-2-pyridinyl]phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0005	uM
3-[3-tert-butylsulfanyl-5-[(5-methyl-2-pyridinyl)methoxy]-1-[[4-(5-methyl-2-pyridinyl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0005	uM
3-[3-tert-butylsulfanyl-5-[(5-methyl-2-pyridinyl)methoxy]-1-[(4-pyridin-3-ylphenyl)methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0005	uM
3-[3-tert-butylsulfanyl-5-[(5-ethyl-2-pyridinyl)methoxy]-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0006	uM
3-[3-tert-butylsulfanyl-1-[[4-(5-methoxypyrimidin-2-yl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0006	uM
3-[3-tert-butylsulfanyl-5-[(5,6-dimethyl-2-pyridinyl)methoxy]-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0006	uM
3-[3-tert-butylsulfanyl-1-[[4-(6-ethoxy-2-pyridinyl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0006	uM
3-[3-tert-butylsulfanyl-1-[[4-(5-fluoro-3-pyridinyl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0006	uM
3-[3-tert-butylsulfanyl-5-[(5-methyl-2-pyridinyl)methoxy]-1-[(4-pyridin-2-ylphenyl)methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0006	uM
3-[3-tert-butylsulfanyl-5-[(6-fluoroquinolin-2-yl)methoxy]-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0007	uM
2-[6-[6-[3-methyl-2-[4-(pyridin-2-ylmethoxy)phenyl]butan-2-yl]-3-pyridinyl]pyridazin-3-yl]propan-2-ol	1940807: Inhibition of FLAP in human Leucocyte membrane incubated for 20 mins by radioactivity based gamma-scintillation counter assay	ic50	0.0007	uM
3-[3-tert-butylsulfanyl-1-[[4-(6-ethoxy-3-pyridinyl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0007	uM
5-[1-tert-butyl-2-[5-chloro-2-(3-methylpyrazol-1-yl)phenyl]benzimidazol-5-yl]pyrimidin-2-amine	1940813: Displacement of [125I]-L-691831 from recombinant human FLAP expressed in Sf9 insect cells incubated for 2 hr by scintillation proximity assay	ic50	0.0007	uM
3-[3-tert-butylsulfanyl-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]-5-(quinoxalin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0007	uM
3-[3-tert-butylsulfanyl-5-[(5-chloro-2-pyridinyl)methoxy]-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0007	uM
3-[3-tert-butylsulfanyl-5-[(5-methoxy-2-pyridinyl)methoxy]-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0007	uM
3-[3-tert-butylsulfanyl-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0008	uM
3-[3-tert-butylsulfanyl-1-[[4-(3-methoxy-2-pyridinyl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0008	uM
5-[2-[(1S,2S,4S)-2-phenyl-2-bicyclo[2.2.1]heptanyl]-4-(quinolin-2-ylmethoxy)phenyl]-3H-1,3,4-oxadiazol-2-one	662426: Displacement of [125I]L-691,831 from 5-lipoxygenase-activating protein in human polymorphonuclear cells	ic50	0.0008	uM
3-[4-[3-[1-[4-(2-aminopyrimidin-5-yl)phenyl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]propanenitrile	1464603: Displacement of [125I]-L-691831 from human FLAP expressed in Sf9 cell membranes after 2 hrs by Topcount method	ic50	0.0010	uM
2-[4-[3-[1-[4-(2-aminopyrimidin-5-yl)phenyl]cyclobutyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]-N-tert-butyl-N-methylacetamide	1464603: Displacement of [125I]-L-691831 from human FLAP expressed in Sf9 cell membranes after 2 hrs by Topcount method	ic50	0.0010	uM
2-[6-[6-[2-[4-(5-methoxy-3-pyridinyl)phenyl]-3-methylbutan-2-yl]-3-pyridinyl]pyridazin-3-yl]propan-2-ol	1940807: Inhibition of FLAP in human Leucocyte membrane incubated for 20 mins by radioactivity based gamma-scintillation counter assay	ic50	0.0011	uM
3-[3-tert-butylsulfanyl-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]-5-[(3-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0011	uM
2-[4-[3-[(1R)-1-[4-(6-amino-3-pyridinyl)phenyl]-1-cyclopropylethyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]-N,N-dimethylacetamide	1200260: Displacement of [125I]-L-691831 from human FLAP expressed in insect SF9 cell membranes after 2 hrs by Topcount analysis	ic50	0.0011	uM
5-[2-[(1S,2R,4S)-2-phenyl-2-bicyclo[2.2.1]heptanyl]-4-(quinolin-2-ylmethoxy)phenyl]-3H-1,3,4-oxadiazole-2-thione	662426: Displacement of [125I]L-691,831 from 5-lipoxygenase-activating protein in human polymorphonuclear cells	ic50	0.0011	uM
5-[2-[(1S,2S,4S)-2-(3-methoxyphenyl)-2-bicyclo[2.2.1]heptanyl]-4-(quinolin-2-ylmethoxy)phenyl]-3H-1,3,4-oxadiazol-2-one	662426: Displacement of [125I]L-691,831 from 5-lipoxygenase-activating protein in human polymorphonuclear cells	ic50	0.0011	uM
cis-(1R,2S)-2-[1-[[2-fluoro-4-(4-methylpiperidin-1-yl)phenyl]methyl]-6-[(3-fluoro-5-methyl-2-pyridinyl)methoxy]benzimidazol-2-yl]cyclohexane-1-carboxylic acid	1940814: Inhibition of N-terminal His6-tagged human FLAP expressed in Sf9 insect cells assessed as inhibition constant incubated for 2 hr by HTRF assay	ki	0.0011	uM
3-[3-tert-butylsulfanyl-5-[(3,5-dimethyl-2-pyridinyl)methoxy]-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0012	uM
2-[4-[3-[(1R)-1-[4-(5-aminopyrazin-2-yl)phenyl]-1-cyclopropylethyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]-N,N-dimethylacetamide	1200260: Displacement of [125I]-L-691831 from human FLAP expressed in insect SF9 cell membranes after 2 hrs by Topcount analysis	ic50	0.0012	uM
5-[4-[(1R)-1-cyclopropyl-1-[5-(1-methylpyrazol-4-yl)-1,2,4-oxadiazol-3-yl]ethyl]phenyl]pyrimidin-2-amine	1200260: Displacement of [125I]-L-691831 from human FLAP expressed in insect SF9 cell membranes after 2 hrs by Topcount analysis	ic50	0.0013	uM
3-[5-[[(2S)-1-acetyl-2,3-dihydroindol-2-yl]methoxy]-3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]indol-2-yl]-2,2-dimethylpropanoic acid	455267: Binding affinity to FLAP in human PMN derived membrane	ic50	0.0014	uM
3-[3-tert-butylsulfanyl-5-(imidazo[1,2-a]pyridin-2-ylmethoxy)-1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0014	uM
5-[4-[1-(5-phenyl-1,2,4-oxadiazol-3-yl)cyclobutyl]phenyl]pyrimidin-2-amine	1200260: Displacement of [125I]-L-691831 from human FLAP expressed in insect SF9 cell membranes after 2 hrs by Topcount analysis	ic50	0.0014	uM
3-[3-(3,3-dimethylbutanoyl)-1-[[4-(6-ethoxy-3-pyridinyl)phenyl]methyl]-5-[(5-methyl-2-pyridinyl)methoxy]indol-2-yl]-2,2-dimethylpropanoic acid	632049: Inhibition of FLAP in human peripheral leukocytes assessed as inhibition of calcium ionophore A23187-induced LTB4 production after 10 mins by ELISA	ic50	0.0015	uM
5-[5-[(1R)-1-cyclopropyl-1-[5-[1-(oxetan-3-yl)pyrazol-4-yl]-1,2,4-oxadiazol-3-yl]ethyl]-2-pyridinyl]pyrimidin-2-amine	1464603: Displacement of [125I]-L-691831 from human FLAP expressed in Sf9 cell membranes after 2 hrs by Topcount method	ic50	0.0015	uM
3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid	314667: Displacement of [125I]L-691831 from FLAP	ic50	0.0016	uM
5-[4-[(2R)-3-methyl-2-[5-(1-methylpyrazol-4-yl)-1,2,4-oxadiazol-3-yl]butan-2-yl]phenyl]pyrimidin-2-amine	1200260: Displacement of [125I]-L-691831 from human FLAP expressed in insect SF9 cell membranes after 2 hrs by Topcount analysis	ic50	0.0016	uM
5-methyl-3-[2-[(1S,2R,4S)-2-phenyl-2-bicyclo[2.2.1]heptanyl]-4-(quinolin-2-ylmethoxy)phenyl]-1,2,4-oxadiazole	662426: Displacement of [125I]L-691,831 from 5-lipoxygenase-activating protein in human polymorphonuclear cells	ic50	0.0016	uM
3-[5-[[(2S)-1-acetyl-2,3-dihydroindol-2-yl]methoxy]-3-tert-butylsulfanyl-1-[[4-(5-fluoro-2-pyridinyl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	455267: Binding affinity to FLAP in human PMN derived membrane	ic50	0.0017	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
MK-886	affects binding, decreases activity, decreases reaction, increases abundance, increases response to substance (+1 more)	5
Arsenic Trioxide	increases expression, affects cotreatment, decreases expression	4
Tretinoin	affects cotreatment, increases expression	4
sodium arsenite	decreases expression, increases expression	3
(+)-JQ1 compound	decreases expression	2
Zoledronic Acid	increases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, increases expression	2
OTX015	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
imidazopyrazole	increases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
indolo(3,2-b)carbazole	increases expression	1
2-(4-(quinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetic acid	decreases activity, decreases abundance	1
L 655238	decreases reaction, increases abundance, increases response to substance	1
dimethylarsinous acid	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
3-(5-(-1-acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-(4-(5-methoxypyrimidin-2-yl)-benzyl)-1H-indol-2-yl)-2,2-dimethyl-propionic acid	decreases activity	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	decreases expression	1
Carcinogens	decreases expression	1
Cycloheximide	decreases expression, decreases reaction	1

ChEMBL screening assays

116 unique, capped per target: 111 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2050900	Binding	Inhibition of 5-lipoxygenase/FLAP in calcium ionophore-stimulated human whole blood assessed as residual LTB4 level at 10 uM preincubated for 15 mins prior to calcium ionophore-stimulation measured after 15 mins by LC-MS/MS analysis	Structure-activity relationship of nonacidic quinazolinone inhibitors of human microsomal prostaglandin synthase 1 (mPGES 1). — J Med Chem
CHEMBL700005	Functional	Inhibition of calcium ionophore (A23187) stimulated LTB4 formation in human neutrophils	O-alkylcarboxylate oxime and N-hydroxyurea analogs of substituted indole leukotriene biosynthesis inhibitors — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D2I4	Abcam Raji ALOX5AP KO	Cancer cell line	Male
CVCL_UQ15	Abcam Jurkat ALOX5AP KO	Cancer cell line	Male
CVCL_WQ99	Abcam K-562 ALOX5AP KO	Cancer cell line	Female

Clinical trials (associated diseases)

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