CYSLTR2

Summary

CYSLTR2 (cysteinyl leukotriene receptor 2, HGNC:18274) is a protein-coding gene on chromosome 13q14.2, encoding Cysteinyl leukotriene receptor 2 (Q9NS75). Receptor for cysteinyl leukotrienes.

The cysteinyl leukotrienes LTC4, LTD4, and LTE4 are important mediators of human bronchial asthma. Pharmacologic studies have determined that cysteinyl leukotrienes activate at least 2 receptors, the protein encoded by this gene and CYSLTR1. This encoded receptor is a member of the superfamily of G protein-coupled receptors. It seems to play a major role in endocrine and cardiovascular systems.

Source: NCBI Gene 57105 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 65 total — 1 pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• MANE Select transcript: NM_001308476

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18274
Approved symbol	CYSLTR2
Name	cysteinyl leukotriene receptor 2
Location	13q14.2
Locus type	gene with protein product
Status	Approved
Aliases	CysLT(2), CYSLT2R
Ensembl gene	ENSG00000152207
Ensembl biotype	protein_coding
OMIM	605666
Entrez	57105

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 16 protein_coding

ENST00000282018, ENST00000614739, ENST00000617562, ENST00000621321, ENST00000622559, ENST00000682523, ENST00000859943, ENST00000859944, ENST00000859945, ENST00000859946, ENST00000859947, ENST00000859948, ENST00000945011, ENST00000945012, ENST00000945013, ENST00000945014

RefSeq mRNA: 11 — MANE Select: NM_001308476 NM_001308465, NM_001308467, NM_001308468, NM_001308469, NM_001308470, NM_001308471, NM_001308476, NM_001387012, NM_001387013, NM_001387014, NM_020377

CCDS: CCDS9412

Canonical transcript exons

ENST00000682523 — 5 exons

Exon	Start	End
ENSE00003713636	48693438	48693510
ENSE00003713811	48696526	48696626
ENSE00003736457	48691212	48691301
ENSE00003919725	48653929	48654017
ENSE00003920021	48706817	48711226

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 81.02.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5935 / max 221.3067, expressed in 317 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135083	0.9191	241
135082	0.2998	104
135084	0.2107	104
135081	0.1400	79
135080	0.0238	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	81.02	gold quality
monocyte	CL:0000576	79.73	gold quality
leukocyte	CL:0000738	79.39	gold quality
mononuclear cell	CL:0000842	79.37	gold quality
apex of heart	UBERON:0002098	79.06	gold quality
right adrenal gland	UBERON:0001233	78.68	gold quality
left adrenal gland cortex	UBERON:0035825	78.50	gold quality
granulocyte	CL:0000094	78.00	gold quality
left adrenal gland	UBERON:0001234	77.68	gold quality
adrenal cortex	UBERON:0001235	77.04	gold quality
hair follicle	UBERON:0002073	76.57	gold quality
right atrium auricular region	UBERON:0006631	75.40	gold quality
cardiac atrium	UBERON:0002081	73.93	gold quality
adrenal gland	UBERON:0002369	73.78	gold quality
heart left ventricle	UBERON:0002084	73.44	gold quality
cardiac ventricle	UBERON:0002082	72.44	gold quality
pancreatic ductal cell	CL:0002079	71.68	silver quality
heart	UBERON:0000948	70.53	gold quality
lymph node	UBERON:0000029	68.68	gold quality
diaphragm	UBERON:0001103	68.58	gold quality
periodontal ligament	UBERON:0008266	66.99	gold quality
sperm	CL:0000019	66.68	gold quality
colonic epithelium	UBERON:0000397	66.67	gold quality
vermiform appendix	UBERON:0001154	66.47	gold quality
male germ cell	CL:0000015	66.35	gold quality
putamen	UBERON:0001874	65.74	gold quality
anterior cingulate cortex	UBERON:0009835	64.99	gold quality
cingulate cortex	UBERON:0003027	64.97	gold quality
islet of Langerhans	UBERON:0000006	64.89	gold quality
spleen	UBERON:0002106	64.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF7

miRNA regulators (miRDB)

67 targeting CYSLTR2, 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-4425	100.00	67.59	1049
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-578	99.46	68.36	1787

Literature-anchored findings (GeneRIF, showing 40)

• Ca2+ fluxes elicited by CysLT in these vascular endothelial cells emanate from perturbation of the CysLT2R, rather than the expected CysLT1R. (PMID:12816881)
• mast cells express the type 2 receptor for cysLTs (CysLT2R) as well, and that the amount of surface CysLT2R protein increases in response to priming with IL-4 (PMID:13679572)
• Mutations in cysteinyl leukotriene 2 receptor is associated with atopy (PMID:14515063)
• identified three novel exons in the 5’ untranslated region of CYSLTR2 and eight novel polymorphisms; the -1220A > C polymorphism is associated with the development of asthma (PMID:15454733)
• 601A>G coding polymorphism in the CYSLT2 receptor alters the potency of LTD4 (PMID:15475736)
• Endothelial CysLT2R increases vascular permeability & recruits neutrophils via enhanced P-selectin expression. It may participate in hypotensive anaphylaxis. CysLT2R-dependent NO formation interacts with superoxide to form peroxynitrite. (PMID:15545522)
• CysLT 1 expression predominates on inflammatory leukocytes in aspirin-sensitive rhinosinusitis. Effects of cysteinyl leukotrienes on glands and epithelium may be mediated predominantly through cysLT 2. Potentially important therapeutic implications. (PMID:15696087)
• Because LTD4 and thrombin are likely to be formed concomitantly in vivo, cysLT2-R and PAR-1 may cooperate to augment vascular injury. (PMID:16606835)
• CYSLTR2 and ALOX5 polymorphisms may predispose a minority of individuals to excessive cysteinyl-leukotriene concentrations, yielding a distinct asthma phenotype most likely to respond to leukotriene modifier pharmacotherapy. (PMID:17460547)
• CysLT1R and CysLT2R expression in monocytes can be regulated by CysLT itself and T(H)2 cytokines at the transcriptional level. (PMID:17941281)
• Since prostacyclin is a major blood vessel-protective and anti-thrombotic eicosanoid, the EC cysLT(2)-R may limit its otherwise pro-inflammatory actions through a protective Ca(2+)/calcineurin/NFAT-dependent COX-2 feedback loop (PMID:17991613)
• the potential implication of CysLT2 in the inflammatory response through the modulation of chemokine gene transcription. (PMID:18048362)
• Our results reveal that CysLT(2)R can mediate inflammatory reactions in a vascular bed-specific manner by altering transendothelial vesicle transport-based vascular permeability. (PMID:18779380)
• increase in urinary levels is associated with anaphylaxies and eosinophilic pneumonia (PMID:18946233)
• The sequence variants of CysLTR2 may affect its transcription and the stability of its mRNA, resulting in altered expression of CysLTR2 protein, which in turn causes some asthmatics to be susceptible to aspirin hypersensitivity (PMID:19840403)
• Data show functional expression of CysLT1 and 2 receptors on human platelets and demonstrate that CysLTs induced the release of significant amounts of RANTES, which suggests a novel role for human platelets in CysLT-mediated allergic inflammation. (PMID:20433311)
• results indicate that the M201V polymorphism drastically affects CysLT(2) responses to LTD(4) and less to LTC(4) (PMID:20966037)
• upon ligand activation, CysLT(1)R is tyrosine-phosphorylated and released from heterodimers with CysLT(2)R and, subsequently, internalizes from the plasma membrane to the nuclear membrane in a clathrin-, arrestin-3-, and Rab-5-dependent manner (PMID:21203429)
• Cysteinyl leukotriene receptor 2 gene polymorphism -1220 A/C is not associated with atopic dermatitis or psoriasis vulgaris in Japanese patients. (PMID:21352274)
• The synthesis of cys-LTs from LTA(4) by endothelial cells is directly associated with the activation of the CysLT(2) receptor in a typical autocrine fashion. (PMID:21753081)
• There is a protective role against tumor progression for CysLT(2)R and that it highlights new possibilities to regulate the CysLT(2)R. (PMID:22194989)
• increased expression in tonsillar tissues of Chinese children with sleep-disordered breathing (PMID:22634478)
• CysLT2 receptor plays a primary role in the vascular responses in the upper respiratory tract. (PMID:23524649)
• ATRA treatment induces CysLT(2)R mRNA and protein expression in colon cancer cell lines (PMID:23829413)
• Suggest that endothelial and nonendothelial CysLT2R niches have separate roles in mediating inflammatory responses in ischemic/perfusion injury. (PMID:24285579)
• CysLTR-1 and CysLTR-2 are highly expressed in the adenoid tissues from children with AH, suggesting that leukotrienes are involved in the pathogenesis of AH. (PMID:25760841)
• Autocrine activity of cysteinyl leukotrienes in human vascular endothelial cells: Signaling through the CysLT receptor (PMID:25839425)
• CysLT2 receptors were expressed in lung specimens isolated from asthma subjects. Activation of CysLT2 receptors may contribute to antigen-induced bronchoconstriction in certain asthma population. (PMID:26433531)
• findings implicate CYSLTR2 as a uveal melanoma oncogene and highlight the critical role of Galphaq signaling in uveal melanoma pathogenesis (PMID:27089179)
• CysLTRs -1 and -2 seem to be involved in lymphocyte maturation that occurs in tonsils, without influence of allergies. (PMID:27115897)
• The expression of CysLTR1 and CysLTR2 is higher in the lymphocytes of hyperplasic tonsils in nonallergic children (PMID:27221082)
• our study identifies CYSLTR2 L129Q alterations as a previously unrecognized activating mutation in blue nevi, occuring in a mutually exclusive fashion with known GNAQ and GNA11 mutations. (PMID:27934878)
• Its mutation is found in patients with meningeal melanocytic tumour. (PMID:29476293)
• Polymorphisms in the CYSLTR2 gene are associated with asthma, atopy markers and helminth infection in Brazilian individuals, which may lead to protection or risk for such conditions, however, more studies are needed to evaluate the functional of this variants here in described. (PMID:31126515)
• CYSLTR2-mutant melanocytic blue neoplasms frequently exhibit a heavily pigmented exophytic tumor with a silhouette resembling “pigmented epithelioid melanocytoma” rather than usual cellular blue nevus. (PMID:31162285)
• Mutations of GNAQ, GNA11, SF3B1, EIF1AX, PLCB4 and CYSLTR in Uveal Melanoma in Chinese Patients. (PMID:31614358)
• findings indicate that CysLT2R was involved in inflammation and neuronal damage by inducing the activation of microglia M1 polarization and NF-kappaB pathway, inhibiting microglia M1 polarization and promoting microglia polarization toward M2 phenotype which may exerts neuroprotective effects. (PMID:31726033)
• Direct evidence that the GPCR CysLTR2 mutant causative of uveal melanoma is constitutively active with highly biased signaling. (PMID:33288675)
• Involvement of mutant and wild-type CYSLTR2 in the development and progression of uveal nevi and melanoma. (PMID:33588787)
• The CysLT2R receptor mediates leukotriene C4-driven acute and chronic itch. (PMID:33753496)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
caenorhabditis_elegans		WBGENE00016570

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), F2RL3 (ENSG00000127533), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), F2RL2 (ENSG00000164220), F2RL1 (ENSG00000164251), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), F2R (ENSG00000181104), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Protein

Protein identifiers

Cysteinyl leukotriene receptor 2 — Q9NS75 (reviewed: Q9NS75)

Alternative names: G-protein coupled receptor GPCR21, G-protein coupled receptor HG57, HPN321

All UniProt accessions (3): Q9NS75, A0A1B0GXM0, Q5KU17

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for cysteinyl leukotrienes. The response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Stimulation by BAY u9773, a partial agonist, induces specific contractions of pulmonary veins and might also have an indirect role in the relaxation of the pulmonary vascular endothelium. The rank order of affinities for the leukotrienes is LTC4 = LTD4 » LTE4.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed, with highest levels in the heart, placenta, spleen, peripheral blood leukocytes and adrenal gland. In lung, expressed in the interstitial macrophages, and slightly in smooth muscle cells.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (11): NP_001295394, NP_001295396, NP_001295397, NP_001295398, NP_001295399, NP_001295400, NP_001295405, NP_001373941, NP_001373942, NP_001373943, NP_065110 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR004071	Cyst_leuk_rcpt	Family
IPR013311	CLT2_recept	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (21 total): topological domain 8, transmembrane region 7, glycosylation site 4, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
6RZ6	X-RAY DIFFRACTION	2.43
6RZ7	X-RAY DIFFRACTION	2.43
6RZ8	X-RAY DIFFRACTION	2.7
6RZ9	X-RAY DIFFRACTION	2.73
9JH5	ELECTRON MICROSCOPY	2.76
9JH6	ELECTRON MICROSCOPY	2.89
9IXX	ELECTRON MICROSCOPY	3.15
9UAM	ELECTRON MICROSCOPY	3.3
9UAN	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS75-F1	84.68	0.63

Antibody-complex structures (SAbDab): 2 — 9IXX, 9JH5

Functional residue map

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

Disulfide bonds (1): 111–187

Glycosylation sites (4): 20, 26, 30, 181

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-391906	Leukotriene receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-418555	G alpha (s) signalling events
R-HSA-9664535	LTC4-CYSLTR mediated IL4 production

MSigDB gene sets: 164 (showing top): VALK_AML_WITH_FLT3_ITD, GSE45365_NK_CELL_VS_BCELL_DN, REACTOME_EICOSANOID_LIGAND_BINDING_RECEPTORS, TAKADA_GASTRIC_CANCER_COPY_NUMBER_DN, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, AACTTT_UNKNOWN, chr13q14, GAVIN_FOXP3_TARGETS_CLUSTER_P6, GOMF_ICOSANOID_RECEPTOR_ACTIVITY, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_UP, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY

GO Biological Process (5): immune response (GO:0006955), neuropeptide signaling pathway (GO:0007218), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), leukotriene signaling pathway (GO:0061737)

GO Molecular Function (5): cysteinyl leukotriene receptor activity (GO:0001631), galanin receptor activity (GO:0004966), leukotriene receptor activity (GO:0004974), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
GPCR downstream signalling	2
Eicosanoid ligand-binding receptors	1
Anti-inflammatory response favouring Leishmania parasite infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
leukotriene receptor activity	1
neuropeptide receptor activity	1
icosanoid receptor activity	1
leukotriene signaling pathway	1
transmembrane signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYSLTR2	LTC4S	Q16873	930
CYSLTR2	LTB4R2	Q9NPC1	772
CYSLTR2	ALOX5AP	P20292	741
CYSLTR2	PLCB4	Q15147	721
CYSLTR2	ALOX5	P09917	670
CYSLTR2	GNA11	P29992	668
CYSLTR2	LTA4H	P09960	668
CYSLTR2	EIF1AX	P47813	668
CYSLTR2	ALDH18A1	P54886	663
CYSLTR2	GNAQ	P50148	623
CYSLTR2	TBXA2R	P21731	550
CYSLTR2	PTGER3	P43115	535
CYSLTR2	CYSLTR1	Q9Y271	495
CYSLTR2	CDADC1	Q9BWV3	492
CYSLTR2	FNDC3A	Q9Y2H6	490

IntAct

294 interactions, top by confidence:

A	B	Type	Score
DLG1	CYSLTR2	psi-mi:“MI:0915”(physical association)	0.840
DLG1	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.840
CYSLTR2	DLG1	psi-mi:“MI:0915”(physical association)	0.840
CYSLTR2	DLG1	psi-mi:“MI:0407”(direct interaction)	0.840
SCRIB	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.720
DLG4	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.720
CYSLTR2	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.720
CYSLTR2	DLG4	psi-mi:“MI:0407”(direct interaction)	0.720
CYSLTR2	DLG4	psi-mi:“MI:0915”(physical association)	0.720
CYSLTR2	SCRIB	psi-mi:“MI:0915”(physical association)	0.720
DLG3	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.620
MPDZ	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.620
MAGI1	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.620
PDZK1	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.620
SNTB1	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.620
SNTA1	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.620

BioGRID (26): CYSLTR2 (FRET), CYSLTR2 (Affinity Capture-Western), CYSLTR1 (Affinity Capture-Western), CYSLTR2 (Co-localization), CYSLTR1 (Affinity Capture-Western), CYSLTR2 (Two-hybrid), CYSLTR2 (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSLTR2 (Proximity Label-MS), ATP5G2 (Two-hybrid), DBI (Two-hybrid), ENO1 (Two-hybrid), GRIK1 (Two-hybrid), GNAS (Two-hybrid), HSP90B1 (Two-hybrid)

ESM2 similar proteins: A1A5S3, A5PLE7, B0UXR0, B5X337, F5HDK1, F5HF62, F8VQN3, O00421, O18982, O97663, P09703, P32249, P35351, P35374, P46002, P49685, P50052, P51676, P56412, P69332, P69333, Q01035, Q0II78, Q0VDU3, Q14330, Q1RMI1, Q28929, Q3T0E9, Q3U507, Q4R613, Q6IYF9, Q75ZH0, Q83207, Q89609, Q8BZR0, Q8IYL9, Q8K1Z6, Q95N03, Q96P67, Q98146

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, B2GV46, B5X337, D4A7K7, E7FEL0, E9QJ73, F8VQN3, O00270, O08726, O08858, O14842, O14843, O15529, O42179, O43603, O46685, O60755, O77408, O88410, O88626, O88634, O88853, P21109, P23944, P25024, P25025, P35344, P35383, P35414, P41231, P41232, P46092, P46093, P49652, P49682, P49683, P50132, P51675, P51679

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CYSLTR2	“up-regulates activity”	GNAI3	binding
CYSLTR2	“up-regulates activity”	GNAZ	binding
CYSLTR2	“up-regulates activity”	GNAQ	binding
CYSLTR2	“up-regulates activity”	GNA14	binding
“leukotriene D4(1-)”	“up-regulates activity”	CYSLTR2	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Assembly and cell surface presentation of NMDA receptors	8	26.7×	7e-08
Neurexins and neuroligins	9	23.3×	4e-08
Protein-protein interactions at synapses	5	17.5×	3e-04
p75 NTR receptor-mediated signalling	5	12.3×	8e-04
RHOB GTPase cycle	5	10.2×	2e-03
RHOC GTPase cycle	5	9.6×	2e-03
Death Receptor Signaling	5	9.2×	2e-03
RHOA GTPase cycle	7	6.9×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	51.3×	5e-11
protein localization to synapse	5	37.5×	2e-05
receptor clustering	6	36.7×	2e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	34.0×	3e-07
Rho protein signal transduction	5	12.2×	3e-03
regulation of small GTPase mediated signal transduction	6	8.5×	3e-03
cell-cell adhesion	8	8.0×	6e-04
protein localization to plasma membrane	7	7.5×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — CEAD, UM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	49
Likely benign	8
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
685575	GRCh37/hg19 13q14.2(chr13:48817328-49333400)x1	Pathogenic

SpliceAI

138 predictions. Top by Δscore:

Variant	Effect	Δscore
13:48707640:A:T	donor_gain	0.9900
13:48706624:G:GT	donor_gain	0.9800
13:48706625:A:T	donor_gain	0.9800
13:48707643:G:GG	donor_gain	0.9600
13:48706904:G:GT	donor_gain	0.9400
13:48706905:A:T	donor_gain	0.8900
13:48707546:G:GT	donor_gain	0.8700
13:48706929:A:T	donor_gain	0.8600
13:48707547:A:T	donor_gain	0.8600
13:48707639:G:GT	donor_gain	0.8500
13:48707642:A:AG	donor_gain	0.8200
13:48706971:G:T	donor_gain	0.8100
13:48707153:GAT:G	donor_gain	0.7400
13:48707800:C:T	donor_gain	0.7400
13:48706971:G:GT	donor_gain	0.7200
13:48707404:C:G	donor_gain	0.7100
13:48707646:G:A	donor_gain	0.6800
13:48707647:GTT:G	donor_gain	0.6700
13:48707648:TTT:T	donor_gain	0.6700
13:48707810:G:GG	donor_gain	0.6700
13:48709371:CAGTA:C	acceptor_gain	0.6700
13:48707438:G:GA	donor_gain	0.6600
13:48709369:CCCAG:C	acceptor_gain	0.6500
13:48709370:CCA:C	acceptor_gain	0.6400
13:48709372:A:T	acceptor_gain	0.6400
13:48706706:GATA:G	donor_gain	0.6300
13:48707362:G:GT	donor_gain	0.6300
13:48707809:A:AG	donor_gain	0.6300
13:48706646:T:G	donor_gain	0.6200
13:48707638:GGAAA:G	donor_gain	0.6100

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000014108 (13:48698190 G>A,C,T), RS1000050751 (13:48658002 A>T), RS1000091691 (13:48686038 A>G), RS1000205151 (13:48710430 G>A), RS1000241744 (13:48704358 A>G), RS1000272819 (13:48692628 A>C,T), RS1000286945 (13:48710880 G>C), RS1000335924 (13:48655384 C>T), RS1000395861 (13:48711334 T>C), RS1000414866 (13:48664545 A>G), RS1000457496 (13:48670599 G>T), RS1000559133 (13:48692322 T>C), RS1000567559 (13:48662621 T>G), RS1000571686 (13:48674574 T>C), RS1000586102 (13:48681026 T>C)

Disease associations

OMIM: gene MIM:605666 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000539	Abnormality of refraction
HP:0000541	Retinal detachment
HP:0000572	Visual loss
HP:0001098	Abnormal fundus morphology
HP:0007902	Vitreous hemorrhage
HP:0007906	Ocular hypertension
HP:0008494	Inferior lens subluxation
HP:0010920	Zonular cataract
HP:0011499	Mydriasis
HP:0011524	Iris melanoma
HP:0012054	Choroidal melanoma
HP:0012055	Ciliary body melanoma
HP:0012508	Metamorphopsia
HP:0030786	Photopsia
HP:0030800	Abnormal visual accommodation
HP:0100533	Inflammatory abnormality of the eye
HP:0200026	Ocular pain

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002432_3	Response to inhaled corticosteroid treatment in asthma (change in FEV1)	2.000000e-06
GCST003264_1085	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST004025_18	Systemic juvenile idiopathic arthritis	3.000000e-06
GCST007676_1	3-month functional outcome in ischaemic stroke (modified Rankin score)	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0004713	FEV/FVC ratio
EFO:0009603	stroke outcome severity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094254 (PROTEIN FAMILY), CHEMBL4330 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 77,537 (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
CHEMBL21333	PRANLUKAST	4	12,755
CHEMBL603	ZAFIRLUKAST	4	23,220
CHEMBL787	MONTELUKAST	4	26,700
CHEMBL1200681	MONTELUKAST SODIUM	4	10,913
CHEMBL162358	TOMELUKAST	2	1,180
CHEMBL17344	RITOLUKAST	2	515
CHEMBL22776	POBILUKAST	2	2,150
CHEMBL3597634	GEMILUKAST	2	104

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Leukotriene receptors

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
[3H]LTC4	Full agonist	10.54	pKd
[3H]LTD4	Full agonist	9.4	pKd
compound 15b [PMID: 31811124]	Antagonist	9.21	pIC50
HAMI3379	Antagonist	8.42	pIC50
ONO-2570366	Antagonist	7.85	pIC50
BayCysLT2	Antagonist	7.28	pIC50
LTC4	Full agonist	7.24	pEC50
LTD4	Full agonist	6.98	pEC50
N-methyl LTC4	Full agonist	6.91	pEC50
iralukast	Antagonist	6.8	pA2
BAYu9773	Partial agonist	6.4	pIC50
pobilukast	Antagonist	6.2	pA2
compound 13e [PMID: 31811124]	Antagonist	5.74	pIC50
LTE4	Partial agonist	5.72	pIC50
pranlukast	Antagonist	5.44	pIC50
[3H]ICI-198615	Antagonist	5.2	pKd
zafirlukast	Antagonist	5.13	pIC50

Binding affinities (BindingDB)

4 measured of 4 human assays (4 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
cyclopentyl 3-(2-methoxy-4-((o-tolylsulfonyl)carbamoyl)benzyl)-1-methylindole-5-carbamate	KI	0.26 nM
NSC_5311297	KI	2.3 nM
3-(((3-(2-(7-chloroquinoline-2-yl)ethenyl)phenyl)((3-dimethylamino-3-oxopropyl)thio)methyl)thio)propanoic acid	KI	10.4 nM
CAS_134733-55-4	KI	300 nM

ChEMBL bioactivities

556 potent at pChembl≥5 of 579 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.51	IC50	0.031	nM	CHEMBL354129
10.36	IC50	0.044	nM	PRANLUKAST
10.22	IC50	0.06	nM	CHEMBL171021
10.00	Ki	0.1	nM	CHEMBL299837
9.96	IC50	0.11	nM	CHEMBL169790
9.85	IC50	0.14	nM	CHEMBL354530
9.80	IC50	0.16	nM	CHEMBL170191
9.77	IC50	0.17	nM	CHEMBL343934
9.72	IC50	0.19	nM	CHEMBL343934
9.72	IC50	0.19	nM	CHEMBL344180
9.70	IC50	0.2	nM	CHEMBL178221
9.70	Ki	0.2	nM	CHEMBL89768
9.70	Ki	0.2	nM	CHEMBL48927
9.70	Ki	0.2	nM	ICI-198615
9.70	IC50	0.2	nM	CHEMBL313187
9.68	IC50	0.21	nM	CHEMBL139757
9.62	IC50	0.24	nM	CHEMBL313195
9.60	Ki	0.25	nM	CHEMBL299093
9.60	Ki	0.25	nM	CHEMBL51585
9.59	IC50	0.26	nM	CHEMBL314237
9.54	IC50	0.29	nM	CHEMBL414885
9.52	Ki	0.3	nM	CHEMBL297952
9.52	Ki	0.3	nM	CHEMBL296821
9.52	Ki	0.3	nM	ZAFIRLUKAST
9.52	IC50	0.3	nM	CHEMBL368290
9.52	Ki	0.3	nM	CHEMBL412056
9.52	Ki	0.3	nM	CHEMBL50562
9.52	Ki	0.3	nM	CHEMBL300096
9.52	Ki	0.3	nM	CHEMBL49944
9.51	IC50	0.31	nM	CHEMBL3403187
9.47	IC50	0.34	nM	CHEMBL86302
9.47	IC50	0.34	nM	CHEMBL87337
9.47	IC50	0.34	nM	CHEMBL315973
9.47	IC50	0.34	nM	CHEMBL341603
9.46	IC50	0.35	nM	CHEMBL140381
9.43	IC50	0.37	nM	CHEMBL172889
9.43	IC50	0.37	nM	CHEMBL86302
9.40	IC50	0.4	nM	CHEMBL425675
9.38	IC50	0.42	nM	CHEMBL316170
9.38	IC50	0.42	nM	CHEMBL314237
9.38	IC50	0.42	nM	CHEMBL85633
9.37	IC50	0.43	nM	MONTELUKAST
9.37	IC50	0.43	nM	CHEMBL341603
9.36	IC50	0.44	nM	CHEMBL313195
9.33	IC50	0.47	nM	CHEMBL170100
9.32	IC50	0.48	nM	CHEMBL86063
9.31	IC50	0.49	nM	CHEMBL3401689
9.30	Ki	0.5	nM	CHEMBL301616
9.30	IC50	0.5	nM	CHEMBL369421
9.30	IC50	0.5	nM	CHEMBL83797

PubChem BioAssay actives

514 with measured affinity, of 1269 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
4-[(E)-hept-2-enoxy]-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	<0.0001	uM
N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]-4-(4-phenylbutoxy)benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	<0.0001	uM
4-[(E)-oct-2-enoxy]-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0001	uM
4-oct-7-enoxy-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0001	uM
4-oct-2-ynoxy-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0001	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-(cyclobutylcarbamoylamino)-1-methylindazol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0001	uM
cyclopentyl N-[1-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]indazol-6-yl]carbamate	55075: In vitro binding affinity against cysteinyl leukotriene D4 receptor from guinea pig lung membrane	ki	0.0002	uM
4-[(2E)-octa-2,7-dienoxy]-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0002	uM
cyclopentyl N-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-(2-methoxyethyl)indol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0002	uM
sodium 3-[[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-[3-(dimethylamino)-3-oxopropyl]sulfanylmethyl]sulfanylpropanoate	55237: Binding affinity against Cysteinyl leukotriene D4 receptor	ki	0.0002	uM
2-[1-[[(1R)-1-[3-[(E)-2-(5,7-dihydrothieno[3,4-b]pyridin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0002	uM
2-[1-[[(1R)-1-[3-[(E)-2-(7,7-dimethyl-6,8-dihydro-5H-quinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102663: In vitro inhibition of [3H]LTD4 binding to LTD4 receptor of guinea pig lung membrane with human serum albumin (HSA).	ic50	0.0002	uM
2-[1-[[(1R)-3-[2-(2-hydroxypropan-2-yl)phenyl]-1-[3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0002	uM
2,2-diethyl-4-[3-[(7-fluoroquinolin-2-yl)methoxy]anilino]-4-oxobutanoic acid	102803: In vitro for antagonistic activity against LTD4 receptor in guinea pig ileum	ic50	0.0002	uM
4-(3-carboxypropyl)-8-[(E)-2-[4-(4-phenoxybutoxy)phenyl]ethenyl]-2,3-dihydro-1,4-benzoxazine-2-carboxylic acid	1194280: Antagonist activity at human CysLT2 receptor expressed in HEK293 cells assessed as inhibition of LTD4-inudced intracellular calcium influx preincubated for 30 mins before LTD4 addition by Fura2-AM assay	ic50	0.0003	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-[(2-cyclopentylacetyl)amino]-1-methylindol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
cyclopentyl N-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-methylindazol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
cyclopentyl N-[3-[[2-methoxy-4-[(2-methylphenyl)sulfonylcarbamoyl]phenyl]methyl]-1-methylindazol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
cyclopentyl N-[3-[[4-[(2-chlorophenyl)sulfonylcarbamoyl]-2-methoxyphenyl]methyl]-1-methylindazol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
cyclopentyl N-[3-[[4-[(2-bromophenyl)sulfonylcarbamoyl]-2-methoxyphenyl]methyl]-1-methylindazol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
4-[[5-[(2-cyclopentylacetyl)amino]-1-methylindazol-3-yl]methyl]-3-methoxy-N-(2-methylphenyl)sulfonylbenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-[(2-cyclopentylacetyl)amino]-1-methylindazol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-[(2-cyclohexylacetyl)amino]-1-methylindazol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
2-[1-[[(1R)-1-[3-[(E)-2-(7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102663: In vitro inhibition of [3H]LTD4 binding to LTD4 receptor of guinea pig lung membrane with human serum albumin (HSA).	ic50	0.0003	uM
2-[1-[[(1R)-1-[3-[(E)-2-(6,6-dimethyl-5,7-dihydrocyclopenta[b]pyridin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0003	uM
2,2-diethyl-4-[3-[(5-fluoroquinolin-2-yl)methoxy]anilino]-4-oxobutanoic acid	102803: In vitro for antagonistic activity against LTD4 receptor in guinea pig ileum	ic50	0.0003	uM
Zafirlukast	55237: Binding affinity against Cysteinyl leukotriene D4 receptor	ki	0.0003	uM
4-(4-phenylbutoxy)-N-[3-(2H-tetrazol-5-yl)-2,3-dihydro-1,4-benzodioxin-5-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0004	uM
2,2-diethyl-4-[3-[(E)-2-(7-fluoroquinolin-2-yl)ethenyl]anilino]-4-oxobutanoic acid	102803: In vitro for antagonistic activity against LTD4 receptor in guinea pig ileum	ic50	0.0004	uM
Montelukast	102663: In vitro inhibition of [3H]LTD4 binding to LTD4 receptor of guinea pig lung membrane with human serum albumin (HSA).	ic50	0.0004	uM
4-[8-[[4-(4-phenylbutoxy)benzoyl]amino]-2-(2H-tetrazol-5-yl)-2,3-dihydro-1,4-benzoxazin-4-yl]butanoic acid	1194280: Antagonist activity at human CysLT2 receptor expressed in HEK293 cells assessed as inhibition of LTD4-inudced intracellular calcium influx preincubated for 30 mins before LTD4 addition by Fura2-AM assay	ic50	0.0005	uM
4-heptoxy-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0005	uM
4-[(E)-hept-2-enoxy]-N-[3-(2H-tetrazol-5-yl)-2,3-dihydro-1,4-benzodioxin-5-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0005	uM
N-(2-bromophenyl)sulfonyl-4-[[5-[(2-cyclopentylacetyl)amino]-1-methylindol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0005	uM
2-[1-[[(1R)-1-[3-[(E)-2-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0005	uM
4-[3-[(6,7-difluoroquinolin-2-yl)methoxy]anilino]-2,2-diethyl-4-oxobutanoic acid	102803: In vitro for antagonistic activity against LTD4 receptor in guinea pig ileum	ic50	0.0005	uM
2-[1-[[(1R)-3-[2-(2-hydroxypropan-2-yl)phenyl]-1-[3-[(E)-2-(8-methyl-5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0005	uM
2-[1-[[(1R)-1-[3-[(E)-2-(6-butyl-5-methyl-2-pyridinyl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102663: In vitro inhibition of [3H]LTD4 binding to LTD4 receptor of guinea pig lung membrane with human serum albumin (HSA).	ic50	0.0005	uM
2-[1-[[(1R)-3-[2-(2-hydroxypropan-2-yl)phenyl]-1-[3-[(E)-2-(5-methyl-6-propyl-2-pyridinyl)ethenyl]phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0005	uM
4-(3-carboxypropyl)-8-[[4-(5-phenylpentoxy)benzoyl]amino]-2,3-dihydro-1,4-benzoxazine-2-carboxylic acid	1171360: Antagonist activity at human CysLT2 receptor expressed in HEK293 cells assessed as inhibition of LTD4-inudced intracellular calcium influx preincubated for 30 mins before LTD4 addition by Fura2-AM assay	ic50	0.0006	uM
2-[1-[[(1R)-3-[2-(2-hydroxypropan-2-yl)phenyl]-1-[3-[(E)-2-(6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-2-yl)ethenyl]phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0006	uM
4-oct-2-ynoxy-N-[3-(2H-tetrazol-5-yl)-2,3-dihydro-1,4-benzodioxin-5-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0007	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-(cyclopentylcarbamoylamino)-1-methylindol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0007	uM
2-[1-[[(1R)-1-[3-[(E)-2-(2,3-dihydrothieno[3,2-b]pyridin-5-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0007	uM
2-[1-[[(1R)-3-[2-(2-hydroxypropan-2-yl)phenyl]-1-[3-[(E)-2-(7-methyl-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)ethenyl]phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0007	uM
1,1,1-trifluoro-N-[3-[[(2R,3S,4R)-6-[(5-fluoro-1,3-benzothiazol-2-yl)methoxy]-4-hydroxy-2-methyl-3,4-dihydro-2H-chromen-3-yl]methyl]phenyl]methanesulfonamide	101446: Ability to antagonize LTD4 receptors isolated from guinea pig lung membranes	ki	0.0007	uM
cyclopentyl N-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-methylindol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0008	uM
4-[3-[(7-chloroquinolin-2-yl)methoxy]anilino]-2,2-diethyl-4-oxobutanoic acid	102803: In vitro for antagonistic activity against LTD4 receptor in guinea pig ileum	ic50	0.0008	uM
2-[1-[[(1R)-1-[3-[(E)-2-(8,8-dimethyl-6,7-dihydro-5H-quinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102663: In vitro inhibition of [3H]LTD4 binding to LTD4 receptor of guinea pig lung membrane with human serum albumin (HSA).	ic50	0.0008	uM
2-[1-[[(1R)-1-[3-[(E)-2-(6-cyclobutyl-2-pyridinyl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0008	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
BAY u9773	affects binding, decreases activity, increases activity, decreases reaction, increases abundance	3
Leukotriene D4	affects binding, decreases reaction, increases abundance, increases activity, increases chemical synthesis (+1 more)	3
Aspirin	affects response to substance	2
Calcium	affects binding, decreases reaction, increases abundance, increases activity	2
Leukotriene C4	affects binding, increases activity, increases abundance	2
Leukotriene E4	affects binding, increases activity, increases abundance	2
inositol 1-phosphate	affects binding, increases activity, increases chemical synthesis	1
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
pranlukast	decreases reaction, affects binding, decreases activity	1
verlukast	affects binding, decreases activity, decreases reaction	1
zafirlukast	decreases activity, decreases reaction, affects binding	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
montelukast	affects binding, decreases activity, decreases reaction	1
2-palmitoylglycerol	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Lead	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	decreases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

74 unique, capped per target: 47 functional, 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4882586	Binding	Human Whole Blood Cys LT a-IgE	Data for DCP probe MRL-SYKi
CHEMBL663197	Functional	Antagonist activity tested against Cysteinyl leukotriene D4 receptor	Development of a series of phenyltetrazole leukotriene D4 (LTD4) receptor antagonists. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H419	CHO-K1/CysLT2	Spontaneously immortalized cell line	Female
CVCL_KU52	CHO-K1 CYSLTR2 Gq	Spontaneously immortalized cell line	Female
CVCL_ZK69	GeneBLAzer CysLT2-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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