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
• GTEx eGene: eQTL in 33 tissues, sQTL in 7 (q < 0.05)
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.98 (unconstrained)
• MANE Select transcript: NM_001395660
• Notable: 58 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 54 — 52 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000407877

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 3, TSL 4: 3

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, ENST00001135088

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.

Highest expression (Bgee): ganglionic eminence, ventricular zone, granulocyte, cortical plate, blood.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LPAR2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 33 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 40 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.1e-47	+0.24	19:19629920:C:G
Adipose Subcutaneous	eqtl	2.3e-34	+0.30	19:19629920:C:G
Lung	eqtl	1.3e-26	+0.31	19:19629920:C:G
Nerve Tibial	eqtl	1.3e-23	+0.33	19:19629920:C:G
Cells Cultured fibroblasts	eqtl	3.9e-18	+0.24	19:19629920:C:G
Muscle Skeletal	eqtl	7.4e-15	+0.33	19:19629920:C:G
Artery Aorta	eqtl	9.5e-15	+0.34	19:19629920:C:G
Adipose Visceral Omentum	eqtl	1.6e-14	+0.26	19:19629920:C:G
Esophagus Muscularis	eqtl	4.3e-13	+0.26	19:19629920:C:G
Heart Left Ventricle	eqtl	4.4e-13	+0.32	19:19623068:T:C
Skin Not Sun Exposed Suprapubic	eqtl	6.9e-10	+0.23	19:19632921:T:G
Spleen	eqtl	9.7e-10	+0.25	19:19629920:C:G
Heart Atrial Appendage	eqtl	1.7e-09	+0.25	19:19629920:C:G
Skin Sun Exposed Lower leg	eqtl	1.4e-08	+0.19	19:19632921:T:G
Lung	sqtl	2.2e-07	-0.37	19:19629920:C:G
Thyroid	eqtl	2.6e-07	+0.18	19:19629920:C:G
Adrenal Gland	eqtl	3.2e-07	+0.28	19:19629920:C:G
Colon Transverse	eqtl	4.4e-07	+0.14	19:19629920:C:G
Breast Mammary Tissue	eqtl	8.9e-07	+0.17	19:19629920:C:G
Whole Blood	sqtl	1.7e-06	-0.27	19:19627745:G:A

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

showing 100 of 283 tissues 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
vermiform appendix	UBERON:0001154	85.28	gold quality
small intestine	UBERON:0002108	84.94	gold quality
right lobe of thyroid gland	UBERON:0001119	84.80	gold quality
pylorus	UBERON:0001166	84.68	gold quality
mouth mucosa	UBERON:0003729	84.45	gold quality
esophagus mucosa	UBERON:0002469	84.30	gold quality
skin of leg	UBERON:0001511	84.29	gold quality
thyroid gland	UBERON:0002046	84.25	gold quality
caecum	UBERON:0001153	84.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.90	gold quality
fundus of stomach	UBERON:0001160	83.85	gold quality
saliva-secreting gland	UBERON:0001044	83.70	gold quality
transverse colon	UBERON:0001157	83.47	gold quality
buccal mucosa cell	CL:0002336	83.46	gold quality
pancreas	UBERON:0001264	82.94	gold quality
Brodmann (1909) area 10	UBERON:0013541	82.86	gold quality
frontal pole	UBERON:0002795	82.73	gold quality
paraflocculus	UBERON:0005351	82.62	gold quality
zone of skin	UBERON:0000014	82.39	gold quality
omental fat pad	UBERON:0010414	82.09	gold quality
peritoneum	UBERON:0002358	82.06	gold quality
prostate gland	UBERON:0002367	81.74	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.61	gold quality
right coronary artery	UBERON:0001625	81.29	gold quality
left uterine tube	UBERON:0001303	81.15	gold quality
middle frontal gyrus	UBERON:0002702	81.13	gold quality
bone marrow	UBERON:0002371	81.03	gold quality
adenohypophysis	UBERON:0002196	80.88	gold quality
right ovary	UBERON:0002118	80.84	gold quality
tendon of biceps brachii	UBERON:0008188	80.82	gold quality
left ovary	UBERON:0002119	80.39	gold quality
bone marrow cell	CL:0002092	80.37	gold quality
cerebellar vermis	UBERON:0004720	80.29	gold quality
pituitary gland	UBERON:0000007	80.13	gold quality
endocervix	UBERON:0000458	79.74	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.64	gold quality
vagina	UBERON:0000996	79.46	gold quality
stromal cell of endometrium	CL:0002255	79.18	gold quality
intestine	UBERON:0000160	78.85	gold quality
palpebral conjunctiva	UBERON:0001812	78.66	gold quality
ovary	UBERON:0000992	78.64	gold quality
rectum	UBERON:0001052	78.59	gold quality
esophagus	UBERON:0001043	78.48	gold quality
metanephros cortex	UBERON:0010533	78.48	gold quality
cardia of stomach	UBERON:0001162	78.43	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	78.23	gold quality
pigmented layer of retina	UBERON:0001782	78.19	gold quality
thymus	UBERON:0002370	78.08	silver quality
descending thoracic aorta	UBERON:0002345	78.01	gold quality
tonsil	UBERON:0002372	78.00	gold quality
ectocervix	UBERON:0012249	77.80	gold quality
spinal cord	UBERON:0002240	77.78	gold quality
colon	UBERON:0001155	77.57	gold quality
anatomical system	UBERON:0000467	77.48	gold quality
multicellular organism	UBERON:0000468	77.29	gold quality
material anatomical entity	UBERON:0000465	77.27	gold quality
mucosa of stomach	UBERON:0001199	77.17	gold quality
large intestine	UBERON:0000059	77.15	gold quality
esophagus squamous epithelium	UBERON:0006920	77.15	gold quality
cingulate cortex	UBERON:0003027	77.09	gold quality
anterior cingulate cortex	UBERON:0009835	77.00	gold quality
trachea	UBERON:0003126	76.96	silver quality
right frontal lobe	UBERON:0002810	76.94	gold quality
right lobe of liver	UBERON:0001114	76.77	gold quality
duodenum	UBERON:0002114	76.73	gold quality
periodontal ligament	UBERON:0008266	76.64	gold quality
ascending aorta	UBERON:0001496	76.62	gold quality
subcutaneous adipose tissue	UBERON:0002190	76.61	gold quality
thoracic aorta	UBERON:0001515	76.50	gold quality
lung	UBERON:0002048	76.34	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	49.0	medium
Stomach 1	tissue	31.6	high
Spinal cord	tissue	20.1
Testis	tissue	19.7	medium
Spleen	tissue	18.8	medium
Appendix	tissue	17.6	medium
Pancreas	tissue	16.5	medium
Lymph node	tissue	16.0	medium
Tonsil	tissue	13.8	medium
Skin 1	tissue	12.6	not detected
Corpus callosum	tissue	12.3
Gallbladder	tissue	12.2	high
Vagina	tissue	11.2	not detected
Medulla oblongata	tissue	10.1
Small intestine	tissue	9.9	medium
Pituitary gland	tissue	9.8
Prostate	tissue	9.3	high
Thymus	tissue	9.3
Choroid plexus	tissue	9.1
Duodenum	tissue	9.0	medium
Salivary gland	tissue	8.3	low
Urinary bladder	tissue	8.0	medium
Midbrain	tissue	7.9
Hippocampus	tissue	7.5	medium
Rectum	tissue	7.3	medium
Parathyroid gland	tissue	7.3	medium
Lung	tissue	7.1	medium
Colon	tissue	6.9	low
Locus coeruleus	tissue	6.9
Fallopian tube	tissue	6.7	medium
Esophagus	tissue	6.5	not detected
Thyroid gland	tissue	6.2	medium
Cervix	tissue	5.0	medium
Ovary	tissue	5.0	low
Substantia nigra	tissue	5.0
Thalamus	tissue	4.6
Breast	tissue	4.3	medium
Postcentral gyrus	tissue	4.2
Seminal vesicle	tissue	4.0	low
Placenta	tissue	4.0	medium
Adipose tissue	tissue	3.9	low
Nucleus accumbens	tissue	3.9
Pons	tissue	3.4
Endometrium 1	tissue	3.4	medium
Superior colliculi	tissue	3.2
Epididymis	tissue	2.3	medium
Adrenal gland	tissue	2.3	medium
Liver	tissue	2.0	not detected
Periaqueductal gray	tissue	1.9
Putamen	tissue	1.8
Smooth muscle	tissue	1.7	low
Retina	tissue	1.6
Kidney	tissue	1.6	medium
Hippocampal formation	tissue	1.6
Tongue	tissue	1.4
Hypothalamus	tissue	1.4
Ventral forebrain	tissue	1.2
Heart muscle	tissue	1.1	medium
Olfactory bulb	tissue	1.0
Septum	tissue	1.0

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (20.1), Dorsal spinal cord (17.5), Ventromedial nucleus (12.5), White matter (12.3), Area parastriata, superior (11.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SNAI2

miRNA regulators (miRDB)

Targeting LPAR2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

18 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.0128, LOEUF 0.977, missense Z 1.05 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000407877 — one region, missense o/e 0.85.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1858422) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
lung inflammation	1
increased airway responsiveness	1
abnormal dendritic cell physiology	1
increased IgE level	1
increased susceptibility to type I hypersensitivity reaction	1
increased tumor necrosis factor secretion	1
decreased interleukin-10 secretion	1
increased interleukin-13 secretion	1
increased airway resistance	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Macaca fascicularis	Q95KH4	98.6%	Diamond
Xenopus laevis	Q9PU16	98.4%	Diamond
Ovis aries	P46628	97.8%	Diamond
Bos taurus	Q28031	97.8%	Diamond
Sus scrofa	Q684M3	86.7%	Diamond
Takifugu rubripes	Q9PUQ8	69.1%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
GMIP	protein-coding	51291
ATP13A1	protein-coding	57130
ZNF14	protein-coding	7561
ZNF101	protein-coding	94039
CILP2	protein-coding	148113
YJEFN3	protein-coding	374887
NDUFA13	protein-coding	51079
PBX4	protein-coding	80714

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 by resolution:

PDB	Title	Method	Resolution (Å)
4P0C	Crystal Structure of NHERF2 PDZ1 Domain in Complex with LPA2	X-RAY DIFFRACTION	1.34
9UVZ	Cryo-EM structure of Lysophosphatidic acid receptor 2 (LPA2)-ARK1 with Ki16425	ELECTRON MICROSCOPY	2.99

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Transporters, G-protein coupled receptors, GPCRs excl olfactory receptors, Lysolipids receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

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)

Type	Positions
S-palmitoyl cysteine	308

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	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

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

8 pathways:

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

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 (4): 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), 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

5 top-level categories:

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

25 GO namespaces:

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
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
G protein-coupled receptor signaling pathway	BP	direct assay
cell surface	CC	direct assay

Protein interactions and networks

STRING

showing 16 of 728 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPAR2	LPAR5	Q9H1C0	887
LPAR2	LPAR4	Q99677	881
LPAR2	LPAR6	P43657	860
LPAR2	ENPP2	Q13822	788
LPAR2	GNAQ	P50148	738
LPAR2	GNA15	P30679	700
LPAR2	GDPD1	Q8N9F7	679
LPAR2	LPA	P08519	669
LPAR2	GDPD3	Q7L5L3	657
LPAR2	GNAI1	P04898	652
LPAR2	GPR87	Q9BY21	643
LPAR2	NHERF2	Q15599	571
LPAR2	AGA	P20933	552
LPAR2	CDA	P32320	552
LPAR2	P2RY10	O00398	547
LPAR2	GNA12	Q03113	547

IntAct

Human interaction partners of LPAR2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
LGALS3	association	0.620	3
CFTR	association	0.500	3
NHERF2	physical association	0.500	2
RAMP1	physical association	0.400	3
RAMP2	physical association	0.400	3
RAMP3	physical association	0.400	3
ATXN1	physical association	0.370	1
EI24	association	0.350	1

BioGRID (131 interactions; top human partners by supporting records): TRIP6 (Two-hybrid; 6 records), SIVA1 (Reconstituted Complex; 3 records), SLC9A3R2 (Affinity Capture-Western; 3 records), HBB (Affinity Capture-MS; 2 records), LGALS3 (Affinity Capture-MS; 2 records), PLCB3 (Reconstituted Complex; 2 records), ACP2 (Affinity Capture-MS), ADORA2B (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ATP13A1 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ATP2C1 (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATXN1 (Two-hybrid), AUP1 (Affinity Capture-MS)

SIGNOR signaling

showing 19 of 25 signaling 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”
LPAR2	“up-regulates activity”	GNAI2	binding
LPAR2	“up-regulates activity”	GNA11	binding
LPAR2	“up-regulates activity”	GNA15	binding
LPAR2	“up-regulates activity”	GNA13	binding
“lysophosphatidic acids”	up-regulates	LPAR2	“chemical activation”
LIPH	up-regulates	LPAR2	binding

Protein complexes (CORUM) (12)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

12 complexes by size:

Complex	Subunits	Members
LPAR2-NHERF2-PLCB3 complex	3	LPAR2, NHERF2, PLCB3
LPAR2-TRIP6-NHERF2 complex, LPA stimulated	3	LPAR2, NHERF2, TRIP6
★ GPR55-LPAR2 complex	2	GPR55, LPAR2
LPAR1-LPAR2 complex	2	LPAR2, LPAR1
LPAR2-LPAR3 complex	2	LPAR2, LPAR3
★ LPAR2-S1PR1 complex	2	LPAR2, S1PR1
LPAR2-S1PR2 complex	2	LPAR2, S1PR2
★ LPAR2-S1PR3 complex	2	LPAR2, S1PR3
GPR4-LPAR2 complex	2	GPR4, LPAR2
GPR68-LPAR2 complex	2	GPR68, LPAR2
LPAR2-SIVA1 complex	2	LPAR2, SIVA1
Lysophosphatidic acid receptor 2	1	LPAR2

Ligand–receptor pairs (CellPhoneDB) (1)

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

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ADGRE5	ligand	Signaling by Lysophosphatidic acid receptor

Disease & clinical

Genetic variants

Variant evidence for LPAR2: 58 ClinVar records (0 pathogenic / likely pathogenic); 8 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 193):

Position(s)	Effect	Δscore	Sites
19:19626541–19626542	donor_loss	1.0000	2
19:19628090–19628091	donor_loss	1.0000	5
19:19624570–19624571	acceptor_loss	0.9900	6
19:19626541–19626542	donor_loss	0.9900	2
19:19624572	acceptor_loss	0.9700
19:19627285–19627286	acceptor_loss	0.9700	6
19:19626542	donor_loss	0.9600
19:19627854	donor_gain	0.9600
19:19626643	acceptor_gain	0.9300
19:19624579	acceptor_gain	0.8800

AlphaMissense

963 missense substitutions predicted likely pathogenic (of 2,211 scored), across 242 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M302	9	0.865	0.980
M204	9	0.854	0.989
D78	8	0.996	0.998
F250	8	0.981	0.999
N50	8	0.969	0.997
N291	8	0.965	0.996
D264	8	0.961	0.976
F63	8	0.949	0.993
D299	8	0.943	0.963
N287	8	0.925	0.997
F201	8	0.918	0.965
D112	8	0.879	0.934
F306	8	0.850	0.960
D32	8	0.844	0.917
F80	8	0.790	0.864
W254	7	0.988	0.997
C171	7	0.979	0.993
C178	7	0.978	0.991
F16	7	0.977	0.992
W104	7	0.958	0.989

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	2.66e-07
Stomach Adenocarcinoma (TCGA)	favorable	0.000175

Disease associations

OMIM: gene MIM:605110 | disease phenotypes:

GWAS associations

8 associations:

Study	Trait	p-value
GCST010002_327	Refractive error	4e-29
GCST010703_63	Brain morphology (MOSTest)	3e-10
GCST008103_170	Bipolar disorder	1e-9
GCST009600_40	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1e-9
GCST002149_11	Schizophrenia	3e-9
GCST008115_31	Bipolar I disorder	3e-9
GCST001413_4	Sphingolipid levels	6e-9
GCST008116_4	Bipolar II disorder	4e-6

EFO canonical traits (from GWAS)

3 canonical traits:

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 (CPIC guideline: no)

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)

148 measured of 190 human assays (190 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL3322514	EC50	0.005 nM
CHEMBL3322513	EC50	0.15 nM
CHEMBL4871014	IC50	1 nM
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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	2 nM	US-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
N-[[4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl]methyl]-6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-amine	IC50	2 nM	US-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
BI-2545 (19)	IC50	2.2 nM
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
1-[4-[4-[[[6-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]pyridazin-3-yl]amino]methyl]phenyl]piperazin-1-yl]ethanone	IC50	3 nM	US-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
3-{[6-(Difluoromethyl)pyridin-3-yl]methoxy}-6-iodopyridazine	IC50	3.4 nM	US-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
CHEMBL3975893	IC50	3.5 nM
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
[3-(3,5-Dichloro-4-octyloxy-benzylamino)-propyl]-phosphonic acid	IC50	6.6 nM
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
CHEMBL2335047	EC50	10 nM
CHEMBL5283300	IC50	10 nM
CHEMBL5290275	IC50	10 nM
CHEMBL5278054	IC50	10 nM
CHEMBL5266099	IC50	10 nM
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-11485727: N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators
CHEMBL2335050	EC50	11 nM
CHEMBL2335051	EC50	12 nM
(R)—N-(1-(1-(1H-indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide	IC50	14 nM
[3-(3,5-Dimethyl-4-octyloxy-benzylamino)-propyl]-phosphonic acid	IC50	15 nM

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

188 with measured affinity, of 481 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 cotreatment, decreases expression, affects 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	increases expression, decreases methylation, decreases reaction	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	increases abundance, affects expression	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)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LPAR2 across ~30M SureChEMBL compounds — explore on Sugi Predict.