LPAR2

Summary

LPAR2 (lysophosphatidic acid receptor 2, HGNC:3168) is a protein-coding gene on chromosome 19p13.11, encoding Lysophosphatidic acid receptor 2 (Q9HBW0). Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities.

This gene encodes a member of family I of the G protein-coupled receptors, as well as the EDG family of proteins. This protein functions as a lysophosphatidic acid (LPA) receptor and contributes to Ca2+ mobilization, a critical cellular response to LPA in cells, through association with Gi and Gq proteins. An alternative splice variant has been described but its full length sequence has not been determined.

Source: NCBI Gene 9170 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 58 total
• Druggable target: yes
• MANE Select transcript: NM_001395660

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3168
Approved symbol	LPAR2
Name	lysophosphatidic acid receptor 2
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	EDG-4, LPA2
Ensembl gene	ENSG00000064547
Ensembl biotype	protein_coding
OMIM	605110
Entrez	9170

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 51 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000407877, ENST00000542587, ENST00000586703, ENST00000588233, ENST00000588461, ENST00000589311, ENST00000590629, ENST00000591042, ENST00000592061, ENST00000862318, ENST00000862319, ENST00000862320, ENST00000862321, ENST00000862322, ENST00000862323, ENST00000862324, ENST00000862325, ENST00000914000, ENST00000914001, ENST00000914002, ENST00000914003, ENST00000914004, ENST00000914005, ENST00000914006, ENST00000914007, ENST00000914008, ENST00000914009, ENST00000914010, ENST00000914011, ENST00000914012, ENST00000914013, ENST00000914014, ENST00000914015, ENST00000914016, ENST00000914017, ENST00000914018, ENST00000914019, ENST00000914020, ENST00000914021, ENST00000914022, ENST00000914023, ENST00000914024, ENST00000914025, ENST00000914026, ENST00000914027, ENST00000914028, ENST00000914029, ENST00000914030, ENST00000957104, ENST00000957105, ENST00000957106, ENST00000957107, ENST00000957108

RefSeq mRNA: 1 — MANE Select: NM_001395660 NM_001395660

CCDS: CCDS12407

Canonical transcript exons

ENST00000407877 — 3 exons

Exon	Start	End
ENSE00001555710	19626543	19627284
ENSE00002838243	19628092	19628220
ENSE00003841756	19623655	19624569

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 98.10.

FANTOM5 (CAGE): breadth broad, TPM avg 8.2412 / max 68.6560, expressed in 816 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180158	6.3091	767
180159	0.9771	229
180157	0.7452	353
180156	0.2098	120

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.10	gold quality
ventricular zone	UBERON:0003053	97.66	gold quality
granulocyte	CL:0000094	96.90	gold quality
cortical plate	UBERON:0005343	96.48	gold quality
blood	UBERON:0000178	95.19	gold quality
right testis	UBERON:0004534	94.10	gold quality
spleen	UBERON:0002106	93.55	gold quality
left testis	UBERON:0004533	93.48	gold quality
endometrium epithelium	UBERON:0004811	93.30	gold quality
monocyte	CL:0000576	91.92	gold quality
mononuclear cell	CL:0000842	91.61	gold quality
leukocyte	CL:0000738	91.48	gold quality
testis	UBERON:0000473	91.33	gold quality
embryo	UBERON:0000922	91.03	gold quality
mucosa of transverse colon	UBERON:0004991	90.89	gold quality
right lung	UBERON:0002167	89.60	gold quality
body of stomach	UBERON:0001161	89.32	gold quality
body of pancreas	UBERON:0001150	89.19	gold quality
lower esophagus mucosa	UBERON:0035834	89.15	gold quality
right uterine tube	UBERON:0001302	88.53	gold quality
upper lobe of left lung	UBERON:0008952	88.31	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.02	gold quality
stomach	UBERON:0000945	86.57	gold quality
upper lobe of lung	UBERON:0008948	86.22	gold quality
gall bladder	UBERON:0002110	86.14	gold quality
minor salivary gland	UBERON:0001830	85.94	gold quality
left lobe of thyroid gland	UBERON:0001120	85.47	gold quality
skin of abdomen	UBERON:0001416	85.41	gold quality
lymph node	UBERON:0000029	85.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SNAI2

miRNA regulators (miRDB)

18 targeting LPAR2, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-1288-3P	96.86	66.95	536
HSA-MIR-759	96.16	66.77	873

Literature-anchored findings (GeneRIF, showing 40)

• demonstrate that two biological fluids, blood plasma and seminal plasma, differentially activate LPA receptors (PMID:12123830)
• results suggested that LPA(2) and LPA(3) may be involved in VEGF expression mediated by LPA signals in human ovarian oncogenesis (PMID:12668280)
• LPA may directly increase the level of cyclin D1 in ovarian cancer cells, increasing their proliferation. (PMID:12759391)
• Upregulation of LPA2 may play a role in carcinogenesis, particularly in postmenopausal breast cancer. (PMID:15535846)
• LPA2 is the major LPA receptor in colon cancer cells and cellular signals by LPA2 are largely mediated through its ability to interact with NHERF2. (PMID:15728708)
• formation of the LPA receptor/PDZ domain-containing RhoGEF complex plays a pivotal role in LPA-induced RhoA activation (PMID:15755723)
• These results demonstrate that MAGI-3 interacts directly with LPA(2) and regulates the ability of LPA(2) to activate Erk and RhoA. (PMID:16904289)
• EDG4 and EDG2 cooperate to promote LPA-stimulated chemotaxis in breast tumor cell lines. (PMID:17496233)
• data suggest that LPA receptor-dependent expression of CTGF and CYR61 represents a common host response after interaction with bacteria. (PMID:17765657)
• lysophosphatidic acid 2 receptor mediates down-regulation of Siva-1 to promote cell survival (PMID:17965021)
• A role for the transgenic lysophosphatidic acid (LPA)2 receptor is identified in regulating smooth muscle cell migratory responses in the context of vascular injury. (PMID:18703779)
• LPA and LPA receptors, LPA(2) as well as LPA(1), represent potential therapeutic targets for patients with MPM (PMID:18754873)
• Expression of LPA2 during ovarian carcinogenesis contributes to ovarian cancer aggressiveness, suggesting that the targeting of LPA production and action may have potential for the treatment of ovarian cancer. (PMID:19001604)
• Switching of LPA receptor expression from LPA3 to LPA1, may be involved in prostate cancer progression and/or androgen independence (PMID:19025891)
• LPA(1) receptor, LPA(2) and LPA(3) receptors-induced VASP phosphorylation is a critical mediator of tumor cell migration initiation (PMID:19081821)
• LPA2 and Gi/Src pathways are significant for LPA-induced COX-2 expression and cell migration that could be a promising drug target for ovarian cancer cell metastasis. (PMID:19116446)
• Data show that CLL cells express LPA receptors LPA(1-5) and VEGF receptors, and the plasma levels of VEGF are elevated in CLL patients. (PMID:19860625)
• show that human microglia express LPA receptor subtypes LPA(1), LPA(2), and LPA(3) on mRNA and protein level. LPA activation of C13NJ cells induced Rho and extracellular signal-regulated kinase activation and enhanced cellular ATP production. (PMID:19899077)
• LPA2 gene mutation may play some role in the pathogenesis of colon cancer. (PMID:20890765)
• MAGI-3 competes with NHERF-2 to negatively regulate LPA2 receptor signaling in colon cancer cells. (PMID:21134377)
• This work shows for the first time that key components of the LPA pathway are modulated following traumatic brain injuries in humans. (PMID:21234797)
• found that LPA receptor 2/3-mediated IL-8 expression occurs through Gi/PI3K/AKT, Gi/PKC and IkappaB/NF-kappaB signaling (PMID:21964883)
• LPA2 and LPA6 receptor subtypes are predominant in both HPAECs and HMVECs (PMID:23084965)
• Lysophosphatidic acid (LPA) increased hepatocellular carcinoma cells cell invasion, which was LPA-receptor dependent. (PMID:23569130)
• LPA1 and LPA2 are major LPA receptor subtypes compared with low-expressed LPA3 in PANC-1 tumor cells. (PMID:24061591)
• Crystal structure of NHERF2 PDZ1 domain complex with C-terminal LPA2 sequence. The PDZ1-LPA2 binding specificity is achieved by hydrogen bonds and hydrophobic contacts with the last four LPA2 residues contributing to specific interactions. (PMID:24613836)
• the RhoA-regulated formin Dia1 is involved in entosis downstream of LPAR2 (PMID:24950964)
• Suggest that LPA2 and LPA3 may function as a molecular switch and play opposing roles during megakaryopoiesis of K562 cells. (PMID:25463482)
• Data show high expression levels of LPAR2 and LPAR1 in endometrial cancer tissue with positive correlations with FIGO stage suggesting them as potential biomarkers for endometrial cancer progression. (PMID:26327335)
• LPAR2 mRNA is up-regulation in colorectal cancer. (PMID:26937138)
• epithelial dysplasia was observed in founder mouse intestine, correlating LPA2 overexpression with epithelial dysplasia. The current study demonstrates that overexpression of LPA2 alone can lead to intestinal dysplasia. (PMID:27124742)
• The results indicate that LPA2 and LPA3 receptors play opposing roles during red blood cells differentiation. (PMID:27244685)
• LPA2 mRNA levels were associated with poorer differentiation, and higher LPA6 levels were associated with microvascular invasion in HCC; both became a risk factor for recurrence after surgical treatment when combined with increased serum ATX levels (PMID:27583415)
• LPA2 expression was associated with HIF-1alpha expression and that a high level of LPA2 was associated with shorter overall survival and was an independent prognostic predictor for breast cancer in Chinese women. (PMID:27805252)
• These results suggest that LPA signaling via LPA2 may play an important role in the regulation of cellular functions in HT1080 cells treated with cisplatin. (PMID:28205098)
• Study shows that due to the high LPAR2 and LPAR4 transcript and protein expression in endometriotic ovarian cysts and positive correlations of both these receptors with the PR-B and ERbeta, respectively, those receptors seem to be the most promising predictors of the endometriotic cysts. (PMID:29621954)
• Investigated the roles of LPA receptors in the regulation of cellular functions during tumor progression in osteosarcoma cell lines. MG63-R7-C cell activities were inhibited by LPA2 knockdown, suggesting that LPA signaling via LPA2 plays an important role in the acquisition of malignant properties during tumor progression in MG-63 cells. (PMID:29859140)
• LPAR2 and LPAR5 regulate cellular functions during tumor progression in fibrosarcoma HT1080 cells. (PMID:30093116)
• It was revealed that LPA may stimulate the expression of Notch1 and Hes family bHLH transcription factor 1, and the phosphorylation of protein kinase B which belongs to the Notch pathway. (PMID:31115486)
• The positive expression rate of LPA2 and KLF5 were statistical different in gastric adenocarcinoma, GIN, and normal gastric tissue (P<0.05). LPA2 positive expression was associated with tumor invasion depth, Lauren type, vascular invasion, local lymph node metastasis, and clinical stage (P<0.05). (PMID:31235682)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lpar2a	ENSDARG00000042338
danio_rerio	lpar2b	ENSDARG00000042561
mus_musculus	Lpar2	ENSMUSG00000031861
rattus_norvegicus	Lpar2	ENSRNOG00000090786

Paralogs (18): CNR1 (ENSG00000118432), MC3R (ENSG00000124089), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), MC5R (ENSG00000176136), S1PR5 (ENSG00000180739), GPR3 (ENSG00000181773), MC2R (ENSG00000185231), CNR2 (ENSG00000188822), LPAR1 (ENSG00000198121), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Lysophosphatidic acid receptor 2 — Q9HBW0 (reviewed: Q9HBW0)

Alternative names: Lysophosphatidic acid receptor Edg-4

All UniProt accessions (5): Q9HBW0, K7EJJ9, K7ELJ6, K7ENG7, K7ER68

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Plays a key role in phospholipase C-beta (PLC-beta) signaling pathway. Stimulates phospholipase C (PLC) activity in a manner that is independent of RALA activation.

Subunit / interactions. Interacts with SLC9A3R2/NHERF2, MAGI3 and PLCB3. Interacts with RALA and GRK2.

Subcellular location. Cell surface. Cell membrane.

Tissue specificity. Expressed most abundantly in testes and peripheral blood leukocytes with less expression in pancreas, spleen, thymus and prostate. Little or no expression in heart, brain, placenta, lung, liver, skeletal muscle, kidney, ovary, small intestine, or colon.

Miscellaneous. PubMed:9525886 cDNA clone has a guanine nucleotide deletion that causes a frameshift near its C-terminal coding region. This likely reflects a somatic mutation in the ovary tumor cells from which the cDNA was isolated and may have altered the function of the encoded receptor, and contributed to transformation of the original ovary cells that formed a tumor.

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

RefSeq proteins (1): NP_001382589* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR004065	LPA_rcpt	Family
IPR004066	LPA_rcpt_EDG4	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (25 total): topological domain 8, transmembrane region 7, mutagenesis site 4, glycosylation site 2, chain 1, short sequence motif 1, lipid moiety-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4P0C	X-RAY DIFFRACTION	1.34
9UVZ	ELECTRON MICROSCOPY	2.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HBW0-F1	85.62	0.61

Functional residue map

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

Post-translational modifications (1): 308

Glycosylation sites (2): 7, 15

Mutagenesis-validated functional residues (4):

Position	Phenotype
345	abolishes interaction with magi3.
346	abolishes interaction with magi3.
347	does not affect interaction with magi3.
348	abolishes interaction with magi3.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-419408	Lysosphingolipid and LPA receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 161 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, MODULE_45, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, MODULE_16, MODULE_308, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, KOYAMA_SEMA3B_TARGETS_UP, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOBP_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (6): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of cytosolic calcium ion concentration (GO:0007204), positive regulation of Rho protein signal transduction (GO:0035025), positive regulation of MAPK cascade (GO:0043410), signal transduction (GO:0007165)

GO Molecular Function (5): G protein-coupled receptor activity (GO:0004930), lipid binding (GO:0008289), PDZ domain binding (GO:0030165), lysophosphatidic acid receptor activity (GO:0070915), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), presynaptic active zone membrane (GO:0048787), glutamatergic synapse (GO:0098978), membrane (GO:0016020), endocytic vesicle (GO:0030139)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
regulation of biological quality	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
protein domain specific binding	1
lysophosphatidic acid binding	1
bioactive lipid receptor activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
presynaptic membrane	1
presynaptic active zone	1
synaptic membrane	1
synapse	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

884 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPAR2	NHERF2	Q15599	943
LPAR2	GNAQ	P50148	941
LPAR2	MAGI3	Q5TCQ9	918
LPAR2	LPAR4	Q99677	888
LPAR2	LPAR5	Q9H1C0	886
LPAR2	LPAR6	P43657	880
LPAR2	GNA12	Q03113	843
LPAR2	ENPP2	Q13822	803
LPAR2	TRIP6	Q15654	747
LPAR2	ARHGEF11	O15085	727
LPAR2	GNA15	P30679	713
LPAR2	LPA	P08519	713
LPAR2	GDPD1	Q8N9F7	702
LPAR2	GDPD3	Q7L5L3	695
LPAR2	GPR87	Q9BY21	678

IntAct

33 interactions, top by confidence:

A	B	Type	Score
NHERF2	CFTR	psi-mi:“MI:0914”(association)	0.940
LPAR2	LGALS3	psi-mi:“MI:0914”(association)	0.620
LPAR2	LGALS3	psi-mi:“MI:0915”(physical association)	0.620
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
CFTR	LPAR2	psi-mi:“MI:0914”(association)	0.500
LPAR2	CFTR	psi-mi:“MI:0915”(physical association)	0.500
LPAR2	NHERF2	psi-mi:“MI:0915”(physical association)	0.500
LPAR2	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	LPAR2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	LPAR2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	LPAR2	psi-mi:“MI:0915”(physical association)	0.400
LPAR2	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
LPAR2	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
ATXN1	LPAR2	psi-mi:“MI:0915”(physical association)	0.370
P		psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
SGCA	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	ZNF316	psi-mi:“MI:0914”(association)	0.350
ATP2A3	UBXN8	psi-mi:“MI:0914”(association)	0.350
LGALS9	LGALS8	psi-mi:“MI:0914”(association)	0.350
TNFRSF10C	PLPP3	psi-mi:“MI:0914”(association)	0.350
LPAR2	EI24	psi-mi:“MI:0914”(association)	0.350
ADORA2B	SCAMP2	psi-mi:“MI:0914”(association)	0.350
B4GAT1	KCNN4	psi-mi:“MI:0914”(association)	0.350

BioGRID (131): LPAR2 (Two-hybrid), Slc9a3r2 (Reconstituted Complex), SLC9A3R2 (Affinity Capture-Western), LPAR2 (Reconstituted Complex), PLCB3 (Reconstituted Complex), PLCB3 (Affinity Capture-Western), HBB (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), TRIP6 (Reconstituted Complex), TRIP6 (Affinity Capture-Western), GIPC1 (Reconstituted Complex), LPAR2 (Two-hybrid), LPAR2 (Negative Genetic), LGALS3 (Affinity Capture-MS), HBB (Affinity Capture-MS)

ESM2 similar proteins: A5D7K8, O35932, O95136, O95977, P21731, P30557, P30987, P34972, P34978, P34979, P34980, P35375, P35408, P37289, P43088, P43114, P43115, P43116, P43117, P43118, P43119, P43252, P43253, P46069, P47752, P47901, P47936, P50131, P52592, P56486, P70263, P70597, P79393, Q13258, Q28691, Q28905, Q62053, Q62928, Q8MJ08, Q95125

Diamond homologs: E7EM37, O02213, O02777, O08530, O42384, O73810, O95136, O95977, P14416, P18089, P19020, P19328, P20272, P20288, P21453, P21554, P22270, P24628, P28286, P30545, P30728, P30951, P34972, P34973, P35412, P35462, P46089, P46095, P46628, P47746, P47752, P47936, P48303, P51651, P52592, P52702, P52703, P53453, P56971, P60026

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
LPAR2	up-regulates	GNA12	binding
LPAR2	up-regulates	GNA13	binding
LPAR2	up-regulates	GNAI1	binding
“3-[({4-[4-({[1-(2-chlorophenyl)ethoxy]carbonyl}amino)-3-methyl-1,2-oxazol-5-yl]phenyl}methyl)sulfanyl]propanoic acid”	down-regulates	LPAR2	“chemical inhibition”
LPAR2	“up-regulates activity”	GNAS	binding
LPAR2	“up-regulates activity”	GNAL	binding
LPAR2	“up-regulates activity”	GNAI1	binding
LPAR2	“up-regulates activity”	GNAI3	binding
LPAR2	“up-regulates activity”	GNAO1	binding
LPAR2	“up-regulates activity”	GNAZ	binding
LPAR2	“up-regulates activity”	GNAQ	binding
LPAR2	“up-regulates activity”	GNA14	binding
“lysophosphatidic acid”	“up-regulates activity”	LPAR2	“chemical activation”
“lysophosphatidic acids”	up-regulates	LPAR2	“chemical activation”
LIPH	up-regulates	LPAR2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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.

GO biological processes:

GO term	Partners	Fold	FDR
calcium ion transport	5	31.2×	1e-04
protein localization to plasma membrane	5	18.8×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	0
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

424 predictions. Top by Δscore:

Variant	Effect	Δscore
19:19624565:CGCCC:C	acceptor_gain	1.0000
19:19626539:TTA:T	donor_loss	1.0000
19:19626540:TACC:T	donor_loss	1.0000
19:19626541:A:AC	donor_gain	1.0000
19:19626541:AC:A	donor_gain	1.0000
19:19626541:ACC:A	donor_gain	1.0000
19:19626541:ACCC:A	donor_loss	1.0000
19:19626542:C:CA	donor_gain	1.0000
19:19626542:CC:C	donor_gain	1.0000
19:19626542:CCC:C	donor_gain	1.0000
19:19626542:CCCA:C	donor_gain	1.0000
19:19626542:CCCAG:C	donor_gain	1.0000
19:19626564:TG:T	donor_gain	1.0000
19:19628087:CTCA:C	donor_loss	1.0000
19:19628088:TCAC:T	donor_loss	1.0000
19:19628089:CACC:C	donor_loss	1.0000
19:19628090:ACC:A	donor_loss	1.0000
19:19624567:CCC:C	acceptor_gain	0.9900
19:19624568:CC:C	acceptor_gain	0.9900
19:19624568:CCC:C	acceptor_gain	0.9900
19:19624568:CCCTG:C	acceptor_loss	0.9900
19:19624569:CC:C	acceptor_gain	0.9900
19:19624569:CCT:C	acceptor_loss	0.9900
19:19624570:C:CC	acceptor_gain	0.9900
19:19624571:T:A	acceptor_loss	0.9900
19:19627281:CCAT:C	acceptor_gain	0.9900
19:19627282:CAT:C	acceptor_gain	0.9900
19:19627282:CATC:C	acceptor_gain	0.9900
19:19628090:A:AC	donor_gain	0.9900
19:19628091:C:CC	donor_gain	0.9900

AlphaMissense

2211 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:19624562:G:C	F250L	0.999
19:19624562:G:T	F250L	0.999
19:19624564:A:G	F250L	0.999
19:19626943:G:C	S114R	0.998
19:19626943:G:T	S114R	0.998
19:19626945:T:G	S114R	0.998
19:19627051:G:C	D78E	0.998
19:19627051:G:T	D78E	0.998
19:19627052:T:A	D78V	0.998
19:19627052:T:C	D78G	0.998
19:19627052:T:G	D78A	0.998
19:19627066:A:C	N73K	0.998
19:19627066:A:T	N73K	0.998
19:19624451:G:C	N287K	0.997
19:19624451:G:T	N287K	0.997
19:19624552:A:G	W254R	0.997
19:19624552:A:T	W254R	0.997
19:19627135:A:C	N50K	0.997
19:19627135:A:T	N50K	0.997
19:19624439:A:C	N291K	0.996
19:19624439:A:T	N291K	0.996
19:19627053:C:G	D78H	0.996
19:19627156:G:C	S43R	0.996
19:19627156:G:T	S43R	0.996
19:19627158:T:G	S43R	0.996
19:19624555:A:G	C253R	0.995
19:19626543:C:G	G248R	0.995
19:19626543:C:T	G248R	0.995
19:19626822:A:G	W155R	0.995
19:19626822:A:T	W155R	0.995

dbSNP variants (sampled 300 via entrez): RS1000175239 (19:19624909 G>A), RS1000340066 (19:19626370 T>C), RS1000938780 (19:19627699 C>G,T), RS1001159277 (19:19629719 C>T), RS1001389523 (19:19627949 G>A,C), RS1001423984 (19:19629399 T>C), RS1002546437 (19:19628822 T>G), RS1002672802 (19:19623394 A>G), RS1003008027 (19:19625872 T>C,G), RS1003445357 (19:19629165 C>T), RS1003522278 (19:19627911 C>T), RS1003690583 (19:19623585 T>C), RS1003959922 (19:19628194 G>C), RS1004010927 (19:19628371 C>T), RS1004049357 (19:19623886 C>T)

Disease associations

OMIM: gene MIM:605110 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001413_4	Sphingolipid levels	6.000000e-09
GCST002149_11	Schizophrenia	3.000000e-09
GCST008103_10	Bipolar disorder	1.000000e-09
GCST008115_2	Bipolar I disorder	3.000000e-09
GCST008116_4	Bipolar II disorder	4.000000e-06
GCST009600_14	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-09
GCST010002_52	Refractive error	4.000000e-29
GCST010703_335	Brain morphology (MOSTest)	3.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder
EFO:0009964	bipolar II disorder
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3724 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Lysophospholipid (LPA) receptors

Most potent curated ligand interactions (20 total), top 20:

Ligand	Action	Affinity	Parameter
Radioprotectin-1	Agonist	11.3	pEC50
LPA	Agonist	8.16	pEC50
H2L5186303	Antagonist	8.05	pIC50
2-oleoyl-LPA	Agonist	8.0	pEC50
AMG-35	Antagonist	7.77	pIC50
compound 15 [PMID: 18178086]	Antagonist	7.77	pIC50
NAEPA	Full agonist	7.52	pEC50
CpY	Agonist	7.5	pEC50
CpX	Agonist	6.9	pEC50
farnesyl monophosphate	Antagonist	6.8	pIC50
oleoyl-thiophosphate	Partial agonist	6.61	pEC50
BrP-LPA	Antagonist	6.33	pIC50
dodecylphosphate	Full agonist	6.2	pEC50
dodecyl-thiophosphate	Partial agonist	6.0	pEC50
AM966	Antagonist	5.8	pIC50
UCM-14216	Antagonist	5.72	pIC50
farnesyl diphosphate	Agonist	5.68	pIC50
decyl dihydrogen phosphate	Full agonist	5.4	pEC50
Ki16425	Antagonist	5.25	pKi
GRI977143	Agonist	4.48	pEC50

Binding affinities (BindingDB)

36 measured of 36 human assays (36 total across all organisms); most potent 36 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[4-[4-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-2-fluorophenyl]piperazin-1-yl]ethanone	IC50	1.5 nM	US-20260001863: NOVEL PYRIDAZINES
1-[4-[4-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-2,2-dimethylpiperazin-1-yl]ethanone	IC50	1.6 nM	US-20260001863: NOVEL PYRIDAZINES
1-[5-[4-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]ethanone	IC50	1.8 nM	US-20260001863: NOVEL PYRIDAZINES
6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]-N-[[4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl]methyl]pyridazin-3-amine	IC50	1.8 nM	US-20260001863: NOVEL PYRIDAZINES
1-[4-[6-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-3-pyridinyl]piperazin-1-yl]ethanone	IC50	1.9 nM	US-20260001863: NOVEL PYRIDAZINES
1-[4-[4-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-3-(trifluoromethyl)phenyl]piperazin-1-yl]ethanone	IC50	1.9 nM	US-20260001863: NOVEL PYRIDAZINES
N-[[4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl]methyl]-6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-amine	IC50	2 nM	US-20260001863: NOVEL PYRIDAZINES
BI-2545 (19)	IC50	2.2 nM	US-12391667: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as Autotaxin (ATX) modulators for the treatment of inflammatory airway or fibrotic diseases
1-[4-[5-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-2-pyridinyl]piperazin-1-yl]ethanone	IC50	2.2 nM	US-20260001863: NOVEL PYRIDAZINES
1-[4-[6-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-3-pyridinyl]piperazin-1-yl]ethanone	IC50	2.2 nM	US-20260001863: NOVEL PYRIDAZINES
N-methyl-N-[1-(4-{[(6-{[6-(trifluoromethyl)pyridin-3-yl]methoxy}pyridazin-3-yl)amino]methyl}phenyl)piperidin-4-yl]acetamide	IC50	2.3 nM	US-20260001863: NOVEL PYRIDAZINES
1-[8-[4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]ethanone	IC50	2.4 nM	US-20260001863: NOVEL PYRIDAZINES
1-[6-[3-fluoro-4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-2,6-diazaspiro[3.3]heptan-2-yl]ethanone	IC50	2.4 nM	US-20260001863: NOVEL PYRIDAZINES
1-[4-[5-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-2-pyridinyl]piperazin-1-yl]ethanone	IC50	2.5 nM	US-20260001863: NOVEL PYRIDAZINES
1-[6-[4-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-2,6-diazaspiro[3.3]heptan-2-yl]ethanone	IC50	2.9 nM	US-20260001863: NOVEL PYRIDAZINES
1-[5-[4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-2,5-diazabicyclo[2.2.2]octan-2-yl]ethanone	IC50	2.9 nM	US-20260001863: NOVEL PYRIDAZINES
1-[4-(4-{[(6-{[6-(Difluoromethyl)pyridin-3-yl]methoxy}pyridazin-3-yl)amino]methyl}-phenyl)piperazin-1-yl]ethan-1-one	IC50	2.9 nM	US-20260001863: NOVEL PYRIDAZINES
1-[4-[4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]piperazin-1-yl]ethanone	IC50	3 nM	US-20260001863: NOVEL PYRIDAZINES
1-[4-[4-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-3-fluorophenyl]piperazin-1-yl]ethanone	IC50	3.3 nM	US-20260001863: NOVEL PYRIDAZINES
3-{[6-(Difluoromethyl)pyridin-3-yl]methoxy}-6-iodopyridazine	IC50	3.4 nM	US-20260001863: NOVEL PYRIDAZINES
1-[4-[4-[[[6-[[6-(difluoromethyl)-5-fluoro-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]piperazin-1-yl]ethanone	IC50	3.5 nM	US-20260001863: NOVEL PYRIDAZINES
1-[6-[2-fluoro-4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-2,6-diazaspiro[3.3]heptan-2-yl]ethanone	IC50	3.7 nM	US-20260001863: NOVEL PYRIDAZINES
N-[(1S,5R)-3-[4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-3-azabicyclo[3.1.0]hexan-6-yl]acetamide	IC50	3.8 nM	US-20260001863: NOVEL PYRIDAZINES
2-[4-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-7-methyl-2,7-diazaspiro[3.4]octan-6-one	IC50	3.9 nM	US-20260001863: NOVEL PYRIDAZINES
1-[5-[4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]ethanone	IC50	3.9 nM	US-20260001863: NOVEL PYRIDAZINES
1-[(3aR,6aS)-2-[4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]ethanone	IC50	4 nM	US-20260001863: NOVEL PYRIDAZINES
1-[(3aR,6aS)-2-[4-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]ethanone	IC50	4.4 nM	US-20260001863: NOVEL PYRIDAZINES
2-[[2-ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2-a]pyridin-3-yl]-methylamino]-4-(4-fluorophenyl)-1,3-thiazole-5-carbonitrile	IC50	5 nM	US-12391667: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as Autotaxin (ATX) modulators for the treatment of inflammatory airway or fibrotic diseases
1-[2-[5-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-2-pyridinyl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone	IC50	5.2 nM	US-20260001863: NOVEL PYRIDAZINES
1-[2-[4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone	IC50	6.2 nM	US-20260001863: NOVEL PYRIDAZINES
1-[2-[4-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone	IC50	6.5 nM	US-20260001863: NOVEL PYRIDAZINES
1-((3aR,3bS,6aR,6bS)-5-(4-(((6-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridazin-3-yl)amino)methyl)phenyl)octahydrocyclobuta[1,2-c:3,4-c′]dipyrrol-2(1H)-yl)ethan-1-one	IC50	7 nM	US-20260001863: NOVEL PYRIDAZINES
1-[(3aR,8aS)-2-(4-{[(6-{[6-(trifluoromethyl)pyridin-3-yl]methoxy}pyridazin-3-yl]amino]methyl}phenyl)-decahydropyrrolo[3,4-dazepin-6-yl]ethan-1-one	IC50	8.6 nM	US-20260001863: NOVEL PYRIDAZINES
1-[2-[5-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-2-pyridinyl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone	IC50	9.2 nM	US-20260001863: NOVEL PYRIDAZINES
1-[2-[6-[[[6-[[6-(difluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]-3-pyridinyl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone	IC50	10.4 nM	US-20260001863: NOVEL PYRIDAZINES
2-[[2-ethyl-8-fluoro-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]imidazo[1,2-a]pyridin-3-yl]-methylamino]-4-(4-fluorophenyl)-1,3-thiazole-5-carbonitrile	IC50	50 nM	US-9670204: Compounds and pharmaceutical compositions thereof for the treatment of inflammatory disorders

ChEMBL bioactivities

177 potent at pChembl≥5 of 196 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	EC50	0.15	nM	CHEMBL3322513
9.60	IC50	0.2512	nM	CHEMBL5397550
9.55	IC50	0.2818	nM	CHEMBL5395244
9.48	IC50	0.3311	nM	CHEMBL5424571
9.46	IC50	0.3467	nM	CHEMBL5424662
9.35	IC50	0.4467	nM	CHEMBL5434096
9.24	IC50	0.5754	nM	CHEMBL5427161
9.22	IC50	0.6026	nM	CHEMBL5405450
9.12	IC50	0.7586	nM	CHEMBL5393777
9.02	IC50	0.955	nM	CHEMBL5424251
8.89	Kd	1.3	nM	CHEMBL5182278
8.70	EC50	2	nM	LYSOPHOSPHATIDIC ACID
8.61	IC50	2.455	nM	CHEMBL5418199
8.52	EC50	3	nM	CHEMBL1222042
8.24	IC50	5.754	nM	CHEMBL5411589
8.18	IC50	6.6	nM	CHEMBL119116
8.17	EC50	6.8	nM	LYSOPHOSPHATIDIC ACID
8.14	Ki	7.2	nM	CHEMBL482498
8.05	IC50	8.9	nM	CHEMBL482498
8.05	IC50	9	nM	CHEMBL482498
8.00	IC50	10	nM	CHEMBL5283300
8.00	IC50	10	nM	CHEMBL5290275
8.00	IC50	10	nM	CHEMBL5278054
8.00	IC50	10	nM	CHEMBL5266099
7.82	IC50	15	nM	CHEMBL119440
7.77	IC50	17	nM	CHEMBL256470
7.75	IC50	18	nM	CHEMBL441826
7.68	Ki	20.8	nM	CHEMBL519002
7.68	Ki	21.1	nM	CHEMBL482497
7.66	IC50	21.8	nM	CHEMBL519002
7.66	IC50	22	nM	CHEMBL519002
7.64	IC50	23	nM	CHEMBL332667
7.58	IC50	26	nM	CHEMBL119256
7.55	IC50	28.3	nM	CHEMBL482497
7.54	EC50	29	nM	LYSOPHOSPHATIDIC ACID
7.54	EC50	28.84	nM	LYSOPHOSPHATIDIC ACID
7.52	EC50	30	nM	CHEMBL117754
7.50	IC50	32	nM	CHEMBL331054
7.48	IC50	33	nM	CHEMBL118783
7.46	IC50	35	nM	CHEMBL270865
7.44	IC50	36	nM	CHEMBL119354
7.40	IC50	40	nM	CHEMBL118860
7.38	IC50	42	nM	CHEMBL118815
7.36	IC50	43.65	nM	CHEMBL5413416
7.35	IC50	44.67	nM	CHEMBL5399159
7.30	EC50	50	nM	CHEMBL3322507
7.26	IC50	55	nM	CHEMBL119413
7.24	IC50	57	nM	CHEMBL117715
7.23	IC50	59	nM	CHEMBL119873
7.22	EC50	60	nM	CHEMBL3322508

PubChem BioAssay actives

185 with measured affinity, of 477 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
5-chloro-2-[4-(1,3-dioxobenzo[de]isoquinolin-2-yl)butylsulfamoyl]benzoic acid	1186831: Agonist activity at human LPA2 expressed in LPA1xLPA2 double knockout mouse MEF cells by Fura-2AM dye based Ca2+ mobilization assay	ec50	<0.0001	uM
2-[4-(1,3-dioxobenzo[de]isoquinolin-2-yl)butylsulfamoyl]-5-fluorobenzoic acid	1186831: Agonist activity at human LPA2 expressed in LPA1xLPA2 double knockout mouse MEF cells by Fura-2AM dye based Ca2+ mobilization assay	ec50	0.0001	uM
methyl N-[5-[4-[(2S)-2-[[8-(2,4-dimethyl-1,3-thiazol-5-yl)quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-4-methyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0003	uM
methyl N-[4-methyl-5-[4-[(2S)-2-[[8-[3-(pyrrolidin-1-ylmethyl)phenyl]quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0003	uM
methyl N-[4-methyl-5-[4-[(2S)-2-[[8-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0003	uM
methyl N-[5-[4-[(2S)-2-[[8-[3-[(dimethylamino)methyl]phenyl]quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-4-methyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0003	uM
methyl N-[4-methyl-5-[4-[(2S)-2-[[8-(2-methyl-3-pyridinyl)quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0004	uM
methyl N-[5-[4-[(2S)-2-[[8-[3-[(dimethylamino)methyl]-4-fluorophenyl]quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-4-methyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0006	uM
methyl N-[4-methyl-5-[4-[(2S)-2-[[8-[4-(pyrrolidin-1-ylmethyl)phenyl]quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0006	uM
methyl N-[5-[4-[(2S)-2-[[8-(3,5-dimethyl-1,2-oxazol-4-yl)quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-4-methyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0008	uM
methyl N-[4-methyl-5-[4-[(2S)-2-[(8-pyridin-3-ylquinazolin-4-yl)amino]propyl]piperazin-1-yl]sulfonyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0010	uM
2-[4-(2,4-dichlorophenoxy)-5-methyl-1H-pyrazol-3-yl]-5-(2H-tetrazol-5-ylmethoxy)phenol	1870906: Binding affinity to LPA2 receptor (unknown origin) by free solution assay-compensated interferometric reader (FSA-CIR) technique	kd	0.0013	uM
[(2R)-2-hydroxy-3-phosphonooxypropyl] (Z)-octadec-9-enoate	1186831: Agonist activity at human LPA2 expressed in LPA1xLPA2 double knockout mouse MEF cells by Fura-2AM dye based Ca2+ mobilization assay	ec50	0.0020	uM
methyl N-[4-methyl-5-[4-[(2S)-2-[[8-(6-methyl-3-pyridinyl)quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0025	uM
(2-hydroxy-3-phosphonooxypropyl) (Z)-octadec-9-enoate	1431850: Agonist activity at LPA2 receptor (unknown origin) expressed in MEF cells assessed as increase in intracellular calcium level measured every 3.42 secs for 70 secs by Fura-2-AM dye based fluorescence assay	ec50	0.0030	uM
N-[(2S)-1-[4-[5-(3,4-dimethyl-1,2-oxazol-5-yl)thiophen-2-yl]sulfonylpiperazin-1-yl]propan-2-yl]-8-(trifluoromethyl)quinazolin-4-amine	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0058	uM
3-[(3,5-dichloro-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0066	uM
(E)-4-[4-[3-[4-[[(E)-3-carboxyprop-2-enoyl]amino]phenoxy]phenoxy]anilino]-4-oxobut-2-enoic acid	408397: Antagonist activity at LPA2 receptor expressed in rat RH7777 cells assessed as inhibition of LPA-induced intracellular calcium concentration	ki	0.0072	uM
N-(1H-benzimidazol-2-yl)-2-phenylcyclopropane-1-carboxamide	1938512: Inhibition of LPA2 receptor (unknown origin)	ic50	0.0100	uM
N-(1H-benzimidazol-2-yl)-2-(2-chlorophenyl)cyclopropane-1-carboxamide	1938512: Inhibition of LPA2 receptor (unknown origin)	ic50	0.0100	uM
N-(1H-benzimidazol-2-yl)-2-(3-methylphenyl)cyclopropane-1-carboxamide	1938512: Inhibition of LPA2 receptor (unknown origin)	ic50	0.0100	uM
N-(6-chloro-1H-benzimidazol-2-yl)-2-phenylcyclopropane-1-carboxamide	1938512: Inhibition of LPA2 receptor (unknown origin)	ic50	0.0100	uM
2-phenyl-N-[6-(trifluoromethyl)-1H-benzimidazol-2-yl]cyclopropane-1-carboxamide	1938512: Inhibition of LPA2 receptor (unknown origin)	ic50	0.0100	uM
3-[(3,5-dimethyl-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0150	uM
N-[(2S)-1-[4-(3,4-dichlorophenyl)sulfonylpiperazin-1-yl]propan-2-yl]-7-methylthieno[3,2-d]pyrimidin-4-amine	320517: Antagonist activity at LPA2 expressed in RH7777 cells with Gi4-protein and aequorin by calcium mobilization assay	ic50	0.0170	uM
3-[(3-bromo-4-decoxy-5-methoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0180	uM
(E)-4-[3-[[(E)-3-carboxyprop-2-enoyl]amino]anilino]-4-oxobut-2-enoic acid	408397: Antagonist activity at LPA2 receptor expressed in rat RH7777 cells assessed as inhibition of LPA-induced intracellular calcium concentration	ki	0.0208	uM
(E)-4-[4-[4-[[(E)-3-carboxyprop-2-enoyl]amino]phenyl]anilino]-4-oxobut-2-enoic acid	408397: Antagonist activity at LPA2 receptor expressed in rat RH7777 cells assessed as inhibition of LPA-induced intracellular calcium concentration	ki	0.0211	uM
3-[(3,5-dibromo-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0230	uM
3-[(4-octylphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0260	uM
2-[[(Z)-octadec-9-enoyl]amino]ethyl dihydrogen phosphate	102982: Agonistic activity against lysophosphatidic acid receptor 2 using [35S]GTP-gamma-S as radioligand tested in vitro	ec50	0.0300	uM
3-[(3-methyl-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0320	uM
3-[(3-bromo-4-heptoxy-5-methoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0330	uM
N-[(2S)-1-[4-(3-chlorophenyl)sulfonylpiperazin-1-yl]propan-2-yl]-7-methylthieno[3,2-d]pyrimidin-4-amine	320517: Antagonist activity at LPA2 expressed in RH7777 cells with Gi4-protein and aequorin by calcium mobilization assay	ic50	0.0350	uM
3-[(3-bromo-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0360	uM
3-[(4-nonylphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0400	uM
3-[(3-bromo-5-methoxy-4-undecoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0420	uM
N-[(2S)-1-[4-[5-(3,4-dimethyl-1,2-oxazol-5-yl)thiophen-2-yl]sulfonylpiperazin-1-yl]propan-2-yl]-7-methylthieno[3,2-d]pyrimidin-4-amine	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0437	uM
methyl N-[4-methyl-5-[4-[(2S)-2-[[8-(trifluoromethyl)quinazolin-4-yl]amino]propyl]piperazin-1-yl]sulfonyl-1,3-thiazol-2-yl]carbamate	2034258: Antagonist activity at human LPA2 receptor expressed in CHO cells assessed as inhibition of LPA-induced calcium mobilization pretreated for 15 mins followed by LPA stimulation by FLIPR analysis	ic50	0.0447	uM
4-bromo-2-[4-(1,3-dioxobenzo[de]isoquinolin-2-yl)butylsulfamoyl]benzoic acid	1186831: Agonist activity at human LPA2 expressed in LPA1xLPA2 double knockout mouse MEF cells by Fura-2AM dye based Ca2+ mobilization assay	ec50	0.0500	uM
3-[(3-chloro-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0550	uM
3-[(3-chloro-5-methoxy-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0570	uM
3-[(3-fluoro-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0590	uM
5-bromo-2-[4-(1,3-dioxobenzo[de]isoquinolin-2-yl)butylsulfamoyl]benzoic acid	1186831: Agonist activity at human LPA2 expressed in LPA1xLPA2 double knockout mouse MEF cells by Fura-2AM dye based Ca2+ mobilization assay	ec50	0.0600	uM
3-[(4-nonoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0740	uM
3-[(3-bromo-5-methoxy-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0800	uM
3-[(3-methoxy-5-methyl-4-octoxyphenyl)methylamino]propylphosphonic acid	204169: Binding affinity to human sphingosine 1-phosphate receptor 4 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0890	uM
dihydroxy-(2-methoxy-3-octadecoxypropoxy)-sulfanylidene-lambda5-phosphane	733692: Agonist activity at human LPA2 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay	ec50	0.1000	uM
(Z)-N-(3-dihydroxyphosphinothioyl-3-oxopropyl)octadec-9-enamide	102982: Agonistic activity against lysophosphatidic acid receptor 2 using [35S]GTP-gamma-S as radioligand tested in vitro	ec50	0.1080	uM
dihydroxy-[(2S)-2-methoxy-3-octadecoxypropoxy]-sulfanylidene-lambda5-phosphane	733692: Agonist activity at human LPA2 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay	ec50	0.1096	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	5
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
asparanin A	increases expression	1
picoxystrobin	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases response to substance	1
Vorinostat	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Ascorbic Acid	decreases methylation, decreases reaction, increases expression	1
Benzo(a)pyrene	decreases methylation, decreases reaction, increases expression	1
Cannabinoids	affects methylation, increases abundance	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Lead	affects expression	1
Methotrexate	affects response to substance	1
Ozone	affects expression, increases abundance	1
Selenium	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	affects cotreatment, decreases expression	1

ChEMBL screening assays

67 unique, capped per target: 46 functional, 21 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1073934	Functional	Antagonist activity at LPA2 receptor expressed in rat RH7777 cells assessed as inhibition of LPA-induced intracellular calcium response	Structure-based drug design identifies novel LPA3 antagonists. — Bioorg Med Chem
CHEMBL2344992	Binding	Intrinsic activity at human LPA2 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay relative to LPA	Phosphorothioate analogs of sn-2 radyl lysophosphatidic acid (LPA): metabolically stabilized LPA receptor agonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7TR	Ubigene A-549 LPAR2 KO	Cancer cell line	Male
CVCL_D8PC	Ubigene HCT 116 LPAR2 KO	Cancer cell line	Male
CVCL_D9IP	Ubigene HEK293 LPAR2 KO	Transformed cell line	Female
CVCL_E0GM	Ubigene HeLa LPAR2 KO	Cancer cell line	Female
CVCL_H521	RH7777/EDG4	Cancer cell line	Female
CVCL_KU54	CHO-K1 EDG4 Gq	Spontaneously immortalized cell line	Female
CVCL_KW95	PathHunter CHO-K1 EDG4 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZK37	Tango EDG4-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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