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): 43 total — 4 pathogenic
• GTEx eGene: eQTL in 17 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 3
• Drug target: yes — 2 curated mechanism-of-action drugs; 5 molecules with ChEMBL bioactivity
• Constraint (gnomAD): pLI 0.13 (intermediate), LOEUF 0.80 (unconstrained)
• 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: 10 — 7 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000380490

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1

ENST00000380490, ENST00000479597, ENST00000617770, ENST00000892335, ENST00000892336, ENST00001004982, ENST00001009368, ENST00001105019, ENST00001117543, ENST00001132306

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.

Highest expression (Bgee): blood, trabecular bone tissue, bone marrow, lung, granulocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ALOX5AP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	2.0e-36	+0.21	13:30738041:A:T
Skin Not Sun Exposed Suprapubic	eqtl	8.2e-07	+0.19	13:30753703:G:T
Spleen	eqtl	1.4e-06	+0.20	13:30738041:A:T
Colon Transverse	eqtl	3.0e-06	+0.20	13:30732962:C:T
Adipose Subcutaneous	eqtl	2.7e-04	-0.14	13:30740037:G:A
Artery Aorta	eqtl	5.3e-04	+0.12	13:30738041:A:T
Esophagus Muscularis	eqtl	2.0e-03	+0.12	13:30738041:A:T
Artery Tibial	eqtl	5.1e-03	-0.09	13:30742803:G:A
Pancreas	eqtl	8.8e-03	+0.13	13:30738041:A:T
Adipose Visceral Omentum	eqtl	1.3e-02	+0.12	13:30738041:A:T
Muscle Skeletal	eqtl	2.0e-02	+0.34	13:30592655:T:G
Brain Hippocampus	eqtl	2.1e-02	-0.20	13:30695145:G:A
Brain Spinal cord cervical c-1	eqtl	2.6e-02	-0.14	13:30742601:G:A
Artery Coronary	eqtl	3.6e-02	-0.21	13:30597849:T:A
Skin Sun Exposed Lower leg	eqtl	3.8e-02	+0.12	13:30767140:C:T
Heart Left Ventricle	eqtl	4.3e-02	+0.28	13:30224124:A:G
Cells EBV-transformed lymphocytes	eqtl	4.6e-02	-0.43	13:30213972:G:C

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

showing 100 of 293 tissues 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
coronary artery	UBERON:0001621	90.34	gold quality
synovial joint	UBERON:0002217	90.25	gold quality
layer of synovial tissue	UBERON:0007616	90.25	gold quality
left adrenal gland cortex	UBERON:0035825	90.20	gold quality
right adrenal gland	UBERON:0001233	90.18	gold quality
spinal cord	UBERON:0002240	90.05	gold quality
caecum	UBERON:0001153	89.87	gold quality
left uterine tube	UBERON:0001303	89.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.50	gold quality
thymus	UBERON:0002370	89.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.78	gold quality
adrenal cortex	UBERON:0001235	88.38	gold quality
rectum	UBERON:0001052	88.24	gold quality
mucosa of urinary bladder	UBERON:0001259	88.02	gold quality
aorta	UBERON:0000947	87.86	gold quality
cranial nerve II	UBERON:0000941	87.53	gold quality
tibial nerve	UBERON:0001323	87.06	gold quality
ileal mucosa	UBERON:0000331	86.90	gold quality
small intestine	UBERON:0002108	86.62	gold quality
minor salivary gland	UBERON:0001830	86.59	gold quality
smooth muscle tissue	UBERON:0001135	86.44	gold quality
adrenal gland	UBERON:0002369	86.43	gold quality
urinary bladder	UBERON:0001255	86.36	gold quality
adipose tissue	UBERON:0001013	85.98	gold quality
tibial artery	UBERON:0007610	85.95	gold quality
popliteal artery	UBERON:0002250	85.93	gold quality
connective tissue	UBERON:0002384	85.65	gold quality
bronchial epithelial cell	CL:0002328	85.57	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.52	gold quality
transverse colon	UBERON:0001157	85.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.06	gold quality
mucosa of transverse colon	UBERON:0004991	84.86	gold quality
body of stomach	UBERON:0001161	84.74	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.68	gold quality
inferior vagus X ganglion	UBERON:0005363	84.63	gold quality
lower esophagus	UBERON:0013473	84.63	gold quality
oral cavity	UBERON:0000167	84.43	gold quality
right ovary	UBERON:0002118	84.39	gold quality
intestine	UBERON:0000160	84.31	gold quality
endocervix	UBERON:0000458	84.28	gold quality
skin of hip	UBERON:0001554	84.23	gold quality
metanephros cortex	UBERON:0010533	84.18	gold quality
decidua	UBERON:0002450	84.17	gold quality
pericardium	UBERON:0002407	83.98	gold quality
large intestine	UBERON:0000059	83.97	gold quality
colon	UBERON:0001155	83.74	gold quality
calcaneal tendon	UBERON:0003701	83.67	gold quality
jejunal mucosa	UBERON:0000399	83.66	gold quality
body of pancreas	UBERON:0001150	83.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.49	gold quality
superficial temporal artery	UBERON:0001614	83.46	gold quality
substantia nigra	UBERON:0002038	83.15	gold quality
sigmoid colon	UBERON:0001159	83.04	gold quality
mouth mucosa	UBERON:0003729	82.79	gold quality
epithelium of bronchus	UBERON:0002031	82.59	gold quality
esophagus	UBERON:0001043	82.51	gold quality
placenta	UBERON:0001987	82.39	gold quality
heart right ventricle	UBERON:0002080	82.37	gold quality
midbrain	UBERON:0001891	82.27	gold quality
bronchus	UBERON:0002185	82.26	gold quality
duodenum	UBERON:0002114	82.13	gold quality
body of uterus	UBERON:0009853	82.02	gold quality
hypothalamus	UBERON:0001898	81.79	gold quality
mucosa of stomach	UBERON:0001199	81.74	gold quality
amniotic fluid	UBERON:0000173	81.57	gold quality
stomach	UBERON:0000945	81.41	gold quality
right uterine tube	UBERON:0001302	81.36	gold quality
right lobe of thyroid gland	UBERON:0001119	81.31	gold quality
pancreas	UBERON:0001264	81.27	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.12	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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	460.3	high
Lung	tissue	172.6	high
Tonsil	tissue	101.2	high
Appendix	tissue	94.9	low
Thymus	tissue	86.7
Lymph node	tissue	72.2	high
Periaqueductal gray	tissue	64.8
Hypothalamus	tissue	64.5
Urinary bladder	tissue	61.2	not detected
Spleen	tissue	59.5	high
Pons	tissue	54.1
Substantia nigra	tissue	48.7
Adipose tissue	tissue	48.2	not detected
Septum	tissue	47.8
Medulla oblongata	tissue	47.1
Spinal cord	tissue	46.8
Corpus callosum	tissue	44.7
Midbrain	tissue	42.5
Thalamus	tissue	40.3
Smooth muscle	tissue	39.7	not detected
Gallbladder	tissue	37.5	not detected
Placenta	tissue	34.9	not detected
Adrenal gland	tissue	34.1	not detected
Amygdala	tissue	32.8
Putamen	tissue	30.6
Hippocampal formation	tissue	30.6
Superior colliculi	tissue	30.0
Ventral forebrain	tissue	28.9
Small intestine	tissue	26.6	not detected
Basal ganglia	tissue	25.9	not detected
Breast	tissue	24.0	not detected
Cerebral cortex	tissue	23.2	medium
Insular cortex	tissue	23.2
Tongue	tissue	23.0
Entorhinal cortex	tissue	22.9
Motor cortex	tissue	22.1
Temporal cortex	tissue	22.1
Prefrontal cortex	tissue	21.5
Colon	tissue	21.3	not detected
Esophagus	tissue	20.5	not detected
Duodenum	tissue	20.3	not detected
Retrosplenial cortex	tissue	20.2
Rectum	tissue	20.1	not detected
Retrosplenial and cingulate cortex	tissue	19.3
Stomach 1	tissue	18.8	not detected
Fallopian tube	tissue	18.5	not detected
Liver	tissue	18.4	not detected
Somatosensory cortex	tissue	18.4
Occipital cortex	tissue	18.3
Cervix	tissue	17.6	not detected
Choroid plexus	tissue	16.3
Seminal vesicle	tissue	14.6	not detected
Locus coeruleus	tissue	13.2
Olfactory bulb	tissue	11.9
Vagina	tissue	11.8	not detected
Salivary gland	tissue	11.1	not detected
Ovary	tissue	10.5	not detected
Endometrium 1	tissue	10.3	not detected
Kidney	tissue	9.9	not detected
Hippocampus	tissue	9.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Lateral funiculus (white matter) (53.9), Ventral spinal cord (46.8), White matter (44.7), Blood vessel (41.0), Dorsal spinal cord (41.0).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting ALOX5AP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

22 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.131, LOEUF 0.795, missense Z 1.01 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000380490 — one region, missense o/e 0.85.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:107505) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased leukotriene level	2
decreased inflammatory response	1
decreased susceptibility to induced arthritis	1
decreased acute inflammation	1
decreased susceptibility to type I hypersensitivity reaction	1
impaired neutrophil recruitment	1
abnormal prostaglandin level	1
abnormal leukotriene level	1
increased prostaglandin level	1
abnormal thromboxane level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	P30354	100.0%	Diamond
Macaca fascicularis	Q2PG08	100.0%	Diamond
Ovis aries	P30358	97.4%	Diamond
Bos taurus	Q148F2	97.4%	Diamond
Equus caballus	P30353	94.8%	Diamond
Oryctolagus cuniculus	P30357	94.8%	Diamond
Sus scrofa	P30356	92.8%	Diamond
Cavia porcellus	A6XA80	91.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC00398	ncRNA	100874158
USPL1	protein-coding	10208
HMGB1	protein-coding	3146
TEX26-AS2	ncRNA	105370145
LINC01066	ncRNA	106144544
TEX26	protein-coding	122046
LINC00545	ncRNA	440132
MEDAG	protein-coding	84935
TRN-GTT2-4	tRNA	100189036
TEX26-AS1	ncRNA	100507064

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 by resolution:

PDB	Title	Method	Resolution (Å)
6VGC	Crystal Structures of FLAP bound to DG-031	X-RAY DIFFRACTION	2.37
6VGI	Crystal Structures of FLAP bound to MK-866	X-RAY DIFFRACTION	2.61
2Q7R	Crystal structure of human FLAP with an iodinated analog of MK-591	X-RAY DIFFRACTION	4
2Q7M	Crystal structure of human FLAP with MK-591	X-RAY DIFFRACTION	4.25

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted membrane proteins, Disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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

3 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-2142700	Biosynthesis of Lipoxins (LX)	curated
R-HSA-2142688	Synthesis of 5-eicosatetraenoic acids	curated
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)	curated
R-HSA-2142753	Arachidonate metabolism	—
R-HSA-9018678	Biosynthesis of specialized proresolving mediators (SPMs)	—
R-HSA-8978868	Fatty acid metabolism	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—

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 (6): 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 (5): nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), nuclear membrane (GO:0031965)

Reactome top-level categories

5 top-level categories:

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

29 GO namespaces:

Category	Terms
nucleus	2
endomembrane system	2
organelle membrane	2
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
intracellular membrane-bounded organelle	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
nuclear envelope	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to calcium ion	BP	direct assay
leukotriene biosynthetic process	BP	direct assay
protein homotrimerization	BP	physical interaction
endoplasmic reticulum	CC	direct assay
membrane	CC	high-throughput assay
nuclear envelope	CC	direct assay
nuclear membrane	CC	direct assay
arachidonate binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,342 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALOX5AP	ALOX5	P09917	970
ALOX5AP	LTA4H	P09960	918
ALOX5AP	MGST1	P10620	891
ALOX5AP	PTGES	O14684	848
ALOX5AP	MGST3	O14880	837
ALOX5AP	COTL1	Q14019	784
ALOX5AP	CYSLTR1	Q9Y271	768
ALOX5AP	CYSLTR2	Q9NS75	725
ALOX5AP	LTB4R	Q15722	610
ALOX5AP	EPHX2	P34913	610
ALOX5AP	PLA2G4A	P47712	602
ALOX5AP	PRKCH	P24723	598
ALOX5AP	ALOX15	P16050	596
ALOX5AP	LTB4R2	Q9NPC1	562
ALOX5AP	NINJ2	Q9NZG7	551

IntAct

Human interaction partners of ALOX5AP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
AQP6	physical association	0.560	3
FFAR2	physical association	0.560	3
GPR42	physical association	0.560	3
NAPB	physical association	0.560	3
OPRM1	physical association	0.560	3
TMEM120B	physical association	0.560	3
FRA10AC1	physical association	0.400	1
CLIC1	physical association	0.370	1

BioGRID (17 interactions; top human partners by supporting records): ALOX5 (Co-localization; 4 records), AQP6 (Two-hybrid), C9orf72 (Affinity Capture-MS), CLIC1 (Two-hybrid), FFAR2 (Two-hybrid), FIS1 (Affinity Capture-MS), FRA10AC1 (Affinity Capture-MS), GPR42 (Two-hybrid), LTC4S (Reconstituted Complex), NAPB (Two-hybrid), OPRM1 (Two-hybrid), SLC29A2 (Two-hybrid), TMEM120B (Two-hybrid)

Ligand–receptor pairs (CellPhoneDB) (5)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

5 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
GPR17		Signaling by Lipoxin/Leukotriene
OXER1		Signaling by Lipoxin/Leukotriene
CYSLTR2		Signaling by Lipoxin/Leukotriene
CYSLTR1		Signaling by Lipoxin/Leukotriene
FPR2		Signaling by Lipoxin/Leukotriene

Disease & clinical

Genetic variants

Variant evidence for ALOX5AP: 43 ClinVar records (4 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	24
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (4)

Showing all 4 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
57637	GRCh38/hg38 13q12.3-13.1(chr13:29654134-32858245)x1	Pathogenic	criteria provided, single submitter	1
59861	GRCh38/hg38 13q12.11-12.3(chr13:18958091-31090460)x3	Pathogenic	criteria provided, single submitter	1
1180526	GRCh37/hg19 13q12.3-13.2(chr13:28925153-34061696)x1	Pathogenic	criteria provided, single submitter	1
148858	GRCh38/hg38 13q12.3-13.3(chr13:29073320-36556014)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ALOX5AP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 21 predictions of 521):

Position(s)	Effect	Δscore	Sites
13:30735676–30735677	donor_loss	1.0000	2
13:30735682	donor_gain	1.0000
13:30735676–30735677	donor_loss	0.9900	2
13:30748510	donor_gain	0.9900
13:30763942–30763943	acceptor_loss	0.9900	6
13:30735676	donor_loss	0.9800
13:30744160–30744161	donor_loss	0.9800	5
13:30763946	acceptor_gain	0.9800
13:30744164	donor_loss	0.9400
13:30744983	donor_gain	0.9300

AlphaMissense

461 missense substitutions predicted likely pathogenic (of 1,058 scored), across 119 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F67	8	0.963	0.998
N59	8	0.962	0.992
F98	8	0.956	0.996
F26	8	0.940	0.988
F121	8	0.826	0.953
F114	8	0.794	0.905
R94	7	0.983	0.998
W72	7	0.969	0.999
S19	7	0.910	0.999
M125	7	0.873	0.976
F50	7	0.862	0.946
C60	7	0.850	0.994
F85	7	0.837	0.941
N23	7	0.799	0.964
G100	6	0.959	0.993
G115	6	0.955	0.995
G75	6	0.951	0.997
Y97	6	0.939	0.996
Q22	6	0.933	0.983
K116	6	0.924	0.983

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	0.000191

Disease associations

OMIM: gene MIM:603700 | disease phenotypes:

HPO phenotypes

3 phenotypes (HPO-id order):

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

GWAS associations

3 associations:

Study	Trait	p-value
GCST007325_41	General risk tolerance (MTAG)	2e-8
GCST002176_1	Adverse response to chemotherapy in breast cancer (alopecia) (cyclophosphamide+epirubicin+/-5FU)	1e-6
GCST002059_5	Non-word repetition	7e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ALOX5AP protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
FIBOFLAPON	Small molecule	3
VELIFLAPON	Small molecule	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 182,518 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL112	ACETAMINOPHEN	4	159,007
CHEMBL93	ZILEUTON	4	21,507
CHEMBL1922660	FIBOFLAPON	3	311
CHEMBL300982	LICOFELONE	2	988
CHEMBL16596	QUIFLAPON	2	705

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs4769060	gemcitabine	Metabolism/PK	Genotypes AG + GG is associated with decreased Cmax and a lower mean AUC when treated with gemcitabine as compared to genotype AA.	PMID:24225399

Binding affinities (BindingDB)

2236 measured of 2389 human assays (2392 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL1922653	IC50	0.3 nM
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-8952177: 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
CHEMBL1922655	IC50	0.4 nM
CHEMBL1922656	IC50	0.4 nM
CHEMBL1922657	IC50	0.4 nM
CHEMBL1922663	IC50	0.4 nM
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-8952177: 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-8952177: 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
MK-591	IC50	0.5 nM
3-[3-tert-Butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic Acid	IC50	0.5 nM
CHEMBL1922532	IC50	0.5 nM
CHEMBL1922642	IC50	0.5 nM
CHEMBL1922658	IC50	0.5 nM
CHEMBL1922659	IC50	0.5 nM
CHEMBL1922662	IC50	0.5 nM
CHEMBL1922665	IC50	0.5 nM
CHEMBL5283430	IC50	0.5 nM
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-8952177: 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
CHEMBL1922643	IC50	0.6 nM
CHEMBL1922645	IC50	0.6 nM
CHEMBL1922661	IC50	0.6 nM
CHEMBL1922664	IC50	0.6 nM
CHEMBL1922666	IC50	0.6 nM
CHEMBL1229205	IC50	0.6 nM
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-8952177: 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-8952177: 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-9079866: Flap modulators
CHEMBL1922646	IC50	0.7 nM
CHEMBL1922647	IC50	0.7 nM
CHEMBL1922660	IC50	0.7 nM
CHEMBL1922524	IC50	0.7 nM
CHEMBL1922525	IC50	0.7 nM
CHEMBL5269712	IC50	0.7 nM
CHEMBL5274418	IC50	0.7 nM
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-8952177: 1,2,6-substituted benzimidazoles as FLAP modulators
CHEMBL1922654	IC50	0.8 nM
CHEMBL1922523	IC50	0.8 nM
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-8952177: 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-8952177: 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

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 1203 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	increases response to substance, decreases abundance, affects binding, decreases activity, decreases reaction (+1 more)	5
Arsenic Trioxide	decreases expression, increases expression, affects cotreatment	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

4 cell lines: 3 cancer cell line, 1 transformed 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_F4YP	EDITGENE ALOX5AP Knockout HEK293 Cell Line	Transformed cell line	Female
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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ALOX5AP across ~30M SureChEMBL compounds — explore on Sugi Predict.