LPAR5

Summary

LPAR5 (lysophosphatidic acid receptor 5, HGNC:13307) is a protein-coding gene on chromosome 12p13.31, encoding Lysophosphatidic acid receptor 5 (Q9H1C0). Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities.

This gene encodes a member of the rhodopsin class of G protein-coupled transmembrane receptors. This protein transmits extracellular signals from lysophosphatidic acid to cells through heterotrimeric G proteins and mediates numerous cellular processes. Many G protein receptors serve as targets for pharmaceutical drugs. Transcript variants of this gene have been described.

Source: NCBI Gene 57121 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 64 total
• GTEx eGene: eQTL in 15 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.40 (intermediate), LOEUF 1.74 (unconstrained)
• MANE Select transcript: NM_020400
• Notable: 64 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13307
Approved symbol	LPAR5
Name	lysophosphatidic acid receptor 5
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	KPG_010, LPA5
Ensembl gene	ENSG00000184574
Ensembl biotype	protein_coding
OMIM	606926
Entrez	57121

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000329858

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 5: 1

ENST00000329858, ENST00000431922, ENST00000540335, ENST00000889787, ENST00000889789, ENST00000889791, ENST00000889792, ENST00000889794, ENST00000960206, ENST00001143797

RefSeq mRNA: 2 — MANE Select: NM_020400 NM_001142961, NM_020400

CCDS: CCDS8553

Canonical transcript exons

ENST00000329858 — 2 exons

Exon	Start	End
ENSE00001297856	6618835	6621464
ENSE00001402010	6635907	6635959

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 90.30.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1575 / max 225.6890, expressed in 681 samples.

Highest expression (Bgee): gingival epithelium, gingiva, esophagus squamous epithelium, ileal mucosa, oral cavity.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LPAR5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	3.4e-54	+0.87	12:6638412:G:C
Thyroid	eqtl	1.2e-07	+0.26	12:6638412:G:C
Adipose Subcutaneous	eqtl	3.1e-06	+0.17	12:6635698:G:C
Artery Tibial	eqtl	8.7e-05	+0.14	12:6635698:G:C
Whole Blood	eqtl	1.9e-04	+0.43	12:6633394:T:C
Spleen	eqtl	4.8e-04	+0.22	12:6638129:G:A
Esophagus Gastroesophageal Junction	eqtl	1.8e-03	+0.22	12:6635698:G:C
Esophagus Muscularis	eqtl	2.0e-03	+0.21	12:6638129:G:A
Lung	eqtl	2.1e-03	+0.15	12:6635698:G:C
Spleen	sqtl	2.6e-03	-0.88	12:6638869:C:T
Nerve Tibial	eqtl	1.9e-02	+0.10	12:6635698:G:C
Colon Sigmoid	eqtl	2.1e-02	+0.18	12:5637644:G:T
Cells EBV-transformed lymphocytes	sqtl	2.3e-02	-0.47	12:6635663:G:C
Heart Left Ventricle	eqtl	2.7e-02	+0.13	12:6471210:A:G
Adrenal Gland	eqtl	2.8e-02	+0.17	12:6635698:G:C
Adipose Visceral Omentum	eqtl	3.9e-02	+0.09	12:6635698:G:C
Skin Not Sun Exposed Suprapubic	eqtl	4.4e-02	-0.26	12:6395751:C:G

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
129140	4.0160	601
129139	0.6513	218
129142	0.2326	125
129143	0.1384	70
129138	0.0596	34
129141	0.0357	15
129135	0.0239	10

Top tissues by expression

showing 100 of 247 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	90.30	gold quality
gingiva	UBERON:0001828	89.24	gold quality
esophagus squamous epithelium	UBERON:0006920	89.12	gold quality
ileal mucosa	UBERON:0000331	88.58	gold quality
oral cavity	UBERON:0000167	88.05	gold quality
colonic mucosa	UBERON:0000317	87.02	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.73	gold quality
mucosa of transverse colon	UBERON:0004991	86.37	gold quality
esophagus mucosa	UBERON:0002469	85.98	gold quality
palpebral conjunctiva	UBERON:0001812	85.09	gold quality
jejunal mucosa	UBERON:0000399	85.04	gold quality
amniotic fluid	UBERON:0000173	84.64	gold quality
lower esophagus mucosa	UBERON:0035834	84.02	gold quality
endothelial cell	CL:0000115	84.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.23	gold quality
granulocyte	CL:0000094	80.50	gold quality
duodenum	UBERON:0002114	80.34	gold quality
blood	UBERON:0000178	79.56	gold quality
germinal epithelium of ovary	UBERON:0001304	79.24	gold quality
rectum	UBERON:0001052	78.98	gold quality
spleen	UBERON:0002106	78.68	gold quality
inferior vagus X ganglion	UBERON:0005363	77.50	gold quality
vagina	UBERON:0000996	77.39	gold quality
leukocyte	CL:0000738	77.22	gold quality
lymph node	UBERON:0000029	77.09	gold quality
monocyte	CL:0000576	76.70	gold quality
transverse colon	UBERON:0001157	76.68	gold quality
epithelium of nasopharynx	UBERON:0001951	76.56	gold quality
tonsil	UBERON:0002372	76.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.87	gold quality
pharyngeal mucosa	UBERON:0000355	75.74	gold quality
skin of hip	UBERON:0001554	75.57	gold quality
small intestine	UBERON:0002108	75.56	gold quality
pancreatic ductal cell	CL:0002079	75.40	silver quality
heart right ventricle	UBERON:0002080	75.01	gold quality
zone of skin	UBERON:0000014	74.96	gold quality
skin of leg	UBERON:0001511	74.94	gold quality
vermiform appendix	UBERON:0001154	74.67	gold quality
medial globus pallidus	UBERON:0002477	74.47	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	74.28	gold quality
skin of abdomen	UBERON:0001416	74.10	gold quality
spinal cord	UBERON:0002240	74.02	gold quality
heart left ventricle	UBERON:0002084	73.56	gold quality
cardiac ventricle	UBERON:0002082	73.40	gold quality
apex of heart	UBERON:0002098	73.36	gold quality
mammalian vulva	UBERON:0000997	73.27	gold quality
mouth mucosa	UBERON:0003729	73.16	gold quality
placenta	UBERON:0001987	73.01	gold quality
penis	UBERON:0000989	72.90	gold quality
jejunum	UBERON:0002115	72.83	gold quality
esophagus	UBERON:0001043	72.68	gold quality
corpus epididymis	UBERON:0004359	72.19	gold quality
body of stomach	UBERON:0001161	71.97	gold quality
substantia nigra	UBERON:0002038	71.86	gold quality
intestine	UBERON:0000160	71.68	gold quality
parietal pleura	UBERON:0002400	71.63	gold quality
layer of synovial tissue	UBERON:0007616	71.53	gold quality
midbrain	UBERON:0001891	71.44	gold quality
upper leg skin	UBERON:0004262	71.36	gold quality
globus pallidus	UBERON:0001875	71.30	gold quality
minor salivary gland	UBERON:0001830	71.20	gold quality
cardiac muscle of right atrium	UBERON:0003379	71.20	gold quality
caecum	UBERON:0001153	71.01	gold quality
subthalamic nucleus	UBERON:0001906	70.76	gold quality
large intestine	UBERON:0000059	70.70	gold quality
saliva-secreting gland	UBERON:0001044	70.56	gold quality
colon	UBERON:0001155	70.27	gold quality
stomach	UBERON:0000945	70.10	gold quality
superior surface of tongue	UBERON:0007371	70.09	gold quality
epithelial cell of pancreas	CL:0000083	69.25	silver quality
medulla oblongata	UBERON:0001896	69.08	gold quality
ventral tegmental area	UBERON:0002691	68.87	gold quality
superior vestibular nucleus	UBERON:0007227	68.85	gold quality
oviduct epithelium	UBERON:0004804	68.39	gold quality
decidua	UBERON:0002450	68.21	gold quality
caput epididymis	UBERON:0004358	68.10	gold quality
superficial temporal artery	UBERON:0001614	67.53	gold quality
right adrenal gland cortex	UBERON:0035827	67.52	gold quality
right coronary artery	UBERON:0001625	67.35	gold quality
heart	UBERON:0000948	67.30	gold quality
parotid gland	UBERON:0001831	66.98	silver quality
dorsal plus ventral thalamus	UBERON:0001897	66.94	gold quality
nasal cavity mucosa	UBERON:0001826	66.66	gold quality
prefrontal cortex	UBERON:0000451	66.58	gold quality
right adrenal gland	UBERON:0001233	66.41	gold quality
urinary bladder	UBERON:0001255	66.40	gold quality
tongue	UBERON:0001723	66.10	gold quality
Brodmann (1909) area 46	UBERON:0006483	66.02	gold quality
hypothalamus	UBERON:0001898	65.80	gold quality
gall bladder	UBERON:0002110	65.33	gold quality
left adrenal gland	UBERON:0001234	65.29	gold quality
fundus of stomach	UBERON:0001160	65.23	gold quality
colonic epithelium	UBERON:0000397	65.22	silver quality
bone marrow cell	CL:0002092	64.95	silver quality
nipple	UBERON:0002030	64.94	gold quality
body of tongue	UBERON:0011876	64.63	silver quality
descending thoracic aorta	UBERON:0002345	64.56	gold quality
visceral pleura	UBERON:0002401	64.52	gold quality
Ammon’s horn	UBERON:0001954	64.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.11

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Hypothalamus	tissue	17.2
Periaqueductal gray	tissue	15.0
Medulla oblongata	tissue	14.4
Substantia nigra	tissue	14.1
Spinal cord	tissue	13.9
Septum	tissue	13.4
Corpus callosum	tissue	12.8
Pons	tissue	12.5
Tonsil	tissue	11.6	high
Midbrain	tissue	10.6
Locus coeruleus	tissue	10.2
Vagina	tissue	9.7	not detected
Hippocampus	tissue	9.6	medium
Duodenum	tissue	9.2	high
Thalamus	tissue	9.0
Putamen	tissue	8.9
Colon	tissue	8.4	high
Ventral forebrain	tissue	8.4
Lymph node	tissue	8.3	medium
Amygdala	tissue	8.0
Hippocampal formation	tissue	7.9
Rectum	tissue	7.8	high
Small intestine	tissue	7.5	high
Superior colliculi	tissue	7.4
Esophagus	tissue	7.2	high
Stomach 1	tissue	6.8	medium
Basal ganglia	tissue	6.8	low
Nucleus accumbens	tissue	6.5
Skin 1	tissue	5.5	not detected
Choroid plexus	tissue	5.5
Spleen	tissue	5.5	medium
Cerebral cortex	tissue	5.2	medium
Insular cortex	tissue	5.2
Placenta	tissue	5.1	medium
Appendix	tissue	5.0	medium
Prefrontal cortex	tissue	4.5
Entorhinal cortex	tissue	4.5
Temporal cortex	tissue	4.5
Motor cortex	tissue	4.3
Retrosplenial and cingulate cortex	tissue	4.3
Retrosplenial cortex	tissue	4.1
Salivary gland	tissue	4.0	low
Olfactory bulb	tissue	4.0
Occipital cortex	tissue	3.3
Somatosensory cortex	tissue	3.1
Epididymis	tissue	2.5	medium
Adrenal gland	tissue	2.4	medium
Thymus	tissue	2.4
Heart muscle	tissue	2.1	low
Cerebellum	tissue	2.1
Postcentral gyrus	tissue	2.1
Urinary bladder	tissue	1.9	medium
Lung	tissue	1.7	medium
Gallbladder	tissue	1.6	medium
Fallopian tube	tissue	1.5	medium
Thyroid gland	tissue	1.4	medium
Cervix	tissue	1.3	medium
Breast	tissue	1.2	medium
Seminal vesicle	tissue	1.2	medium
Liver	tissue	1.2	not detected

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Lateral funiculus (white matter) (28.7), Nucleus rhomboideus (23.6), Cervical spinal cord, ventral horn (20.2), Nucleus gracilis (19.9), Nucleus raphe pallidus (18.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LPAR5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 60 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-1183	98.75	67.10	1116

Functional genomics

gnomAD constraint: pLI 0.401, LOEUF 1.74, missense Z -1.17 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000329858 — one region, missense o/e 1.04.

Literature-anchored findings (GeneRIF, showing 28)

• GPR92 is proposed as a fifth LPA receptor, LPA5, which likely has distinct physiological functions in view of its expression pattern. (PMID:16774927)
• FPP and NAG play a role in the sensory nervous system through activation of GPR92 (PMID:18499677)
• Four residues involved in ligand recognition in LPA(5) were identified as follows: R2.60N mutant abolished receptor activation, whereas H4.64E, R6.62A, and R7.32A greatly reduced receptor activation. (PMID:19366702)
• 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)
• LPA4 and LPA5 receptors induce osteoblastic differentiation of human mesenchymal stem cells (PMID:20069565)
• LPA5 is a bona fide LPA receptor on human mast cells responsible for the majority of LPA induced MIP-1beta release. (PMID:21464938)
• It was shown that lysophosphatidic acid 5 receptor transactivated the epidermal growth factor receptor and that inhibition of epidermal growth factor receptor blocked lysophosphatidic acid 5 receptor-dependent activation of NHE3. (PMID:21832242)
• These results suggest that LPA5 may act as a negative regulator of cellular responses in mouse fibroblast 3T3 cells, similar to the case for LPA1. (PMID:24632199)
• MMP-2 and MMP-9 were found in HT1080L5 cells, in comparison with control cells. These results suggest that LPA signaling via LPA5 negatively regulates the cell motile and invasive activities of human sarcoma cells. (PMID:24676544)
• Down-regulation of LPA receptor 5 contributes to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma. (PMID:25294670)
• These results suggest that the diverse roles of LPA4, LPA5 and LPA6 are involved in the activation of tumor progression in pancreatic cancer cells. (PMID:25849892)
• These results suggest that the cell motile activity is regulated through the induction of LPA5 by phorbol ester and anticancer drug treatments in A375cells. (PMID:29309788)
• It signaling may play a key role in the mechanisms underlying neuropathic pain following demyelination in the brain. (PMID:29409686)
• LPAR2 and LPAR5 regulate cellular functions during tumor progression in fibrosarcoma HT1080 cells. (PMID:30093116)
• LPA5 Is an Inhibitory Receptor That Suppresses CD8 T-Cell Cytotoxic Function via Disruption of Early TCR Signaling. (PMID:31231367)
• LPAR5 expression was elevated in A375cells treated with anticancer drugs. The high cell survival of highly migratory A375cells is associated with the low LPAR5 expression. The cell survival of A375cells treated with anticancer drugs was increased by LPA5 knockdown. (PMID:31362892)
• Downregulation of LPAR5 expression can inhibit the physiological process of PTC, and this phenomenon is related to the PI3K/AKT pathway and EMT. (PMID:31902939)
• Lysophosphatidic acid receptor 5 transactivation of TGFBR1 stimulates the mRNA expression of proteoglycan synthesizing genes XYLT1 and CHST3. (PMID:32920014)
• LPAR5 stimulates the malignant progression of non-small-cell lung carcinoma by upregulating MLLT11. (PMID:32964980)
• Lysophosphatidic acid mediates the pathogenesis of psoriasis by activating keratinocytes through LPAR5. (PMID:33452232)
• LPAR5 promotes thyroid carcinoma cell proliferation and migration by activating class IA PI3K catalytic subunit p110beta. (PMID:33540491)
• Control of Intestinal Epithelial Permeability by Lysophosphatidic Acid Receptor 5. (PMID:33975030)
• Interference with lysophosphatidic acid receptor 5 ameliorates oxidized low-density lipoprotein-induced human umbilical vein endothelial cell injury by inactivating NOD-like receptor family, pyrin domain containing 3 inflammasome signaling. (PMID:34662522)
• LPAR5 confers radioresistance to cancer cells associated with EMT activation via the ERK/Snail pathway. (PMID:36199069)
• Infiltration of LPAR5[+] macrophages in osteosarcoma tumor microenvironment predicts better outcomes. (PMID:36591220)
• Potential role of LPAR5 gene in prognosis and immunity of thyroid papillary carcinoma and pan-cancer. (PMID:37037831)
• Emerging roles of lysophosphatidic acid receptor subtype 5 (LPAR5) in inflammatory diseases and cancer. (PMID:37061203)
• Crosstalk between cannabinoid receptor 2 and lysophosphatidic acid receptor 5. (PMID:37187093)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lpar5a	ENSDARG00000010384
danio_rerio	lpar5b	ENSDARG00000068638
mus_musculus	Lpar5	ENSMUSG00000067714
rattus_norvegicus	Lpar5	ENSRNOG00000021401

Paralogs (1): GPR68 (ENSG00000119714)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2685918) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal social investigation	1
decreased anxiety-related response	1
hyperactivity	1
abnormal pain threshold	1
increased thermal nociceptive threshold	1
abnormal associative learning	1
increased vertical activity	1
abnormal nociception after inflammation	1
enhanced coordination	1
hyporesponsive to tactile stimuli	1
enhanced spatial learning	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
Chlorocebus pygerythrus	Q8HZP3	99.7%	Diamond
Meriones unguiculatus	Q99PE3	98.8%	Diamond
Macaca mulatta	P56494	97.4%	Diamond
Macaca fascicularis	Q4R613	97.3%	Diamond
Sus scrofa	P50132	95.6%	Diamond
Bos taurus	Q1JQB3	95.3%	Diamond
Ovis aries	Q28756	94.1%	Diamond
Mesocricetus auratus	Q76JU8	88.0%	Diamond
Gallus gallus	P32250	83.8%	Diamond
Callorhinchus milii	A0A4W3GG95	73.4%	Diamond
Salmo salar	B5X337	72.6%	Diamond
Oreochromis niloticus	Q6BD04	56.7%	Diamond
Fowlpox virus strain NVSL	Q9J5I0	42.7%	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
CHD4	protein-coding	1108
CHD4-AS1	ncRNA	139355233
ING4	protein-coding	51147
SCARNA11	ncRNA	677780
ACRBP	protein-coding	84519
IFFO1	protein-coding	25900
NOP2	protein-coding	4839
ZNF384	protein-coding	171017
PIANP	protein-coding	196500

Protein

Protein identifiers

Lysophosphatidic acid receptor 5 — Q9H1C0 (reviewed: Q9H1C0)

Alternative names: G protein-coupled receptor 92, G protein-coupled receptor 93

All UniProt accessions (2): Q5KU18, Q9H1C0

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities.

Subcellular location. Cell membrane.

Tissue specificity. Not expressed in frontal cortex, basal forebrain, caudate putamen, thalamus, or hippocampus.

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

RefSeq proteins (2): NP_001136433, NP_065133* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (22 total): topological domain 8, transmembrane region 7, compositionally biased region 2, glycosylation site 2, chain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
20ZX	Cryo-EM structure of Gq-coupled LPAR5 in complex with LPA	ELECTRON MICROSCOPY	2.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1C0-F1	84.71	0.66

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Lysolipids receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, UniProt - Evidence at transcript level

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.

Disulfide bonds (1)

Type	Positions
Disulfide bond	94–175

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	4, 9

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: 82 (showing top): GOBP_BEHAVIOR, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_BEHAVIORAL_RESPONSE_TO_PAIN, GOBP_RESPONSE_TO_PAIN, SENESE_HDAC3_TARGETS_DN, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHENG_IMPRINTED_BY_ESTRADIOL, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, ANDERSEN_CHOLANGIOCARCINOMA_CLASS2, ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN

GO Biological Process (3): behavioral response to pain (GO:0048266), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (1): G protein-coupled receptor activity (GO:0004930)

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

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

14 GO namespaces:

Category	Terms
behavior	1
response to pain	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 16 of 820 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPAR5	LPAR2	Q9HBW0	887
LPAR5	LPAR3	Q9UBY5	882
LPAR5	LPAR1	P78351	867
LPAR5	ENPP2	Q13822	722
LPAR5	TAS1R1	Q7RTX1	617
LPAR5	FGF23	Q9GZV9	608
LPAR5	GPRC6A	Q5T6X5	600
LPAR5	GDPD3	Q7L5L3	582
LPAR5	GDPD1	Q8N9F7	580
LPAR5	TAS1R3	Q7RTX0	537
LPAR5	MRGPRD	Q8TDS7	534
LPAR5	GNA12	Q03113	501
LPAR5	GPR119	Q8TDV5	495
LPAR5	CASR	P41180	461
LPAR5	FFAR4	Q5NUL3	429
LPAR5	TAS1R2	Q8TE23	429

IntAct

Human interaction partners of LPAR5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
PIK3CB	physical association	0.400	1

BioGRID (4 interactions; top human partners by supporting records): ATG7 (Phenotypic Enhancement), NUDT21 (Affinity Capture-RNA), RNF123 (Affinity Capture-MS), TOP3B (Affinity Capture-RNA)

SIGNOR signaling

7 signaling interactions:

A	Effect	B	Mechanism
LPAR5	“up-regulates activity”	GNAI1	binding
LPAR5	“up-regulates activity”	GNAI3	binding
LPAR5	“up-regulates activity”	GNAO1	binding
LPAR5	“up-regulates activity”	GNAZ	binding
LPAR5	“up-regulates activity”	GNA12	binding
LPAR5	“up-regulates activity”	GNA13	binding
“lysophosphatidic acid”	“up-regulates activity”	LPAR5	“chemical activation”

Protein complexes (CORUM) (1)

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

1 complexes by size:

Complex	Subunits	Members
CNR2-LPAR5 complex	2	CNR2, LPAR5

Disease & clinical

Genetic variants

Variant evidence for LPAR5: 64 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 17 predictions of 190):

Position(s)	Effect	Δscore	Sites
12:6621465–6621466	acceptor_loss	0.9900	5
12:6626475	acceptor_gain	0.9900
12:6621465	acceptor_loss	0.9800
12:6635905–6635906	donor_loss	0.9800	4
12:6635906	donor_loss	0.9600
12:6624019	donor_gain	0.9400
12:6631690	acceptor_gain	0.9400
12:6635864	donor_gain	0.9400
12:6624005	donor_gain	0.8900
12:6631684	acceptor_gain	0.8600

AlphaMissense

666 missense substitutions predicted likely pathogenic (of 2,341 scored), across 195 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
D68	8	0.974	0.989
D293	8	0.950	0.981
D118	8	0.937	0.973
F247	8	0.927	0.989
N40	8	0.920	0.980
F47	8	0.906	0.964
F304	8	0.903	0.981
F101	8	0.888	0.966
F200	8	0.885	0.985
F111	8	0.868	0.929
C94	7	0.981	0.993
C175	7	0.972	0.984
F176	7	0.948	0.975
F243	7	0.928	0.973
F179	7	0.924	0.975
W184	7	0.923	0.992
W87	7	0.907	0.988
N104	7	0.902	0.984
F71	7	0.898	0.940
W146	7	0.895	0.988

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Thyroid Carcinoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Thyroid Carcinoma (TCGA)	favorable	0.000548

Disease associations

OMIM: gene MIM:606926 | disease phenotypes:

GWAS associations

6 associations:

Study	Trait	p-value
GCST010242_198	HDL cholesterol levels	1e-16
GCST90002404_505	Red cell distribution width	5e-13
GCST010244_111	Triglyceride levels	4e-12
GCST90002396_565	Mean reticulocyte volume	2e-11
GCST010241_372	Apolipoprotein A1 levels	1e-10
GCST90002392_51	Mean corpuscular volume	7e-9

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5700 (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 (10 total), top 10:

Ligand	Action	Affinity	Parameter
alkyl glycerol phosphate 18:1	Full agonist	8.7	pEC50
LPA	Agonist	7.9	pEC50
compound 66 [PMID: 36126387]	Antagonist	7.5	pIC50
AS2717638	Antagonist	7.42	pIC50
farnesyl monophosphate	Agonist	7.31	pEC50
compound 65 [PMID: 36126387]	Antagonist	7.2	pIC50
farnesyl diphosphate	Partial agonist	6.54	pEC50
TCLPA5	Antagonist	6.1	pIC50
octyl thiophosphatidic acid	Partial agonist	5.68	pEC50
N-arachidonoylglycine	Partial agonist	4.3	pEC50

Binding affinities (BindingDB)

102 measured of 103 human assays (103 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[[3-(3-fluorophenyl)propyl-[4-(2-methoxyphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	0.3 nM	US-9464060: Compounds
4-[[[4-(2-fluorophenoxy)benzoyl]-[3-(3-fluorophenyl)propyl]amino]methyl]benzoic acid	IC50	0.4 nM	US-9464060: Compounds
4-[[[4-(2-fluorophenoxy)benzoyl]-[3-(2-fluorophenyl)propyl]amino]methyl]benzoic acid	IC50	1 nM	US-9464060: Compounds
4-[[[4-(2-fluorophenoxy)benzoyl]-[(2-phenylcyclopropyl)methyl]amino]methyl]benzoic acid	IC50	1 nM	US-9464060: Compounds
CHEMBL4871014	IC50	1 nM
4-[[[4-(2-fluorophenoxy)benzoyl]-[(4-methoxyphenyl)methyl]amino]methyl]benzoic acid	IC50	2 nM	US-9464060: Compounds
4-[[[4-(2-methoxyphenoxy)benzoyl]-(3-phenylpropyl)amino]methyl]benzoic acid	IC50	2 nM	US-9464060: Compounds
4-[[[4-(2-fluorophenoxy)benzoyl]-[(3-methoxyphenyl)methyl]amino]methyl]benzoic acid	IC50	4 nM	US-9464060: Compounds
4-[[cyclopropylmethyl-[4-(2-methoxyphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	4 nM	US-9464060: Compounds
4-[[[4-(2-methoxyphenoxy)benzoyl]-(2,2,2-trifluoroethyl)amino]methyl]benzoic acid	IC50	4 nM	US-9464060: Compounds
4-[[[4-(2-methoxyphenoxy)benzoyl]-propylamino]methyl]benzoic acid	IC50	5 nM	US-9464060: Compounds
methyl 4-[[butyl-[4-(2-methoxyphenoxy)benzoyl]amino]methyl]benzoate	IC50	5 nM	US-9464060: Compounds
4-[[benzyl-[4-(2-fluorophenoxy)benzoyl]amino]methyl]benzoic acid	IC50	6 nM	US-9464060: Compounds
2-fluoro-4-[[[4-(2-fluorophenoxy)benzoyl]-[(3-methoxyphenyl)methyl]amino]methyl]benzoic acid	IC50	6 nM	US-9464060: Compounds
4-[[[4-(2-fluorophenoxy)benzoyl]-[(2S)-2-hydroxy-3-phenylpropyl]amino]methyl]benzoic acid	IC50	7 nM	US-9464060: Compounds
4-[[[4-(2-chlorophenoxy)benzoyl]-(cyclopropylmethyl)amino]methyl]benzoic acid	IC50	7 nM	US-9464060: Compounds
4-[[2,2-difluoropropyl-[4-(2-methoxyphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	7 nM	US-9464060: Compounds
4-[[cyclopropylmethyl-[2-fluoro-4-(2-methoxyphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	7 nM	US-9464060: Compounds
4-[[cyclopropylmethyl-[4-(2-fluoro-6-methoxyphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	7 nM	US-9464060: Compounds
4-[[[4-(2-fluorophenoxy)benzoyl]-[(2-fluorophenyl)methyl]amino]methyl]benzoic acid	IC50	9 nM	US-9464060: Compounds
4-[[[4-(2-methoxyphenoxy)benzoyl]-(3,3,3-trifluoropropyl)amino]methyl]benzoic acid	IC50	9 nM	US-9464060: Compounds
CHEMBL2335047	EC50	10 nM
4-[[[4-(2-fluorophenoxy)benzoyl]-(4-phenylbutyl)amino]methyl]benzoic acid	IC50	11 nM	US-9464060: Compounds
4-[[benzyl-[4-(2-methylphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	11 nM	US-9464060: Compounds
4-[[benzyl-[4-(2,6-difluorophenoxy)benzoyl]amino]methyl]benzoic acid	IC50	11 nM	US-9464060: Compounds
4-[[benzyl-[4-(2-chloro-6-fluorophenoxy)benzoyl]amino]methyl]benzoic acid	IC50	11 nM	US-9464060: Compounds
CHEMBL2335050	EC50	11 nM
4-[[[4-(2-fluorophenoxy)benzoyl]-[(2R)-2-hydroxy-3-phenylpropyl]amino]methyl]benzoic acid	IC50	12 nM	US-9464060: Compounds
4-[[[4-(2-methoxyphenoxy)benzoyl]-(2-methylpropyl)amino]methyl]benzoic acid	IC50	12 nM	US-9464060: Compounds
4-[[cyclopropylmethyl-[5-(2-methoxyphenoxy)pyridine-2-carbonyl]amino]methyl]benzoic acid	IC50	12 nM	US-9464060: Compounds
CHEMBL2335051	EC50	12 nM
4-[[cyclopropylmethyl-[4-(4-fluoro-2-methoxyphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	13 nM	US-9464060: Compounds
4-[[[4-(2-methylphenoxy)benzoyl]-(2-phenylethyl)amino]methyl]benzoic acid	IC50	14 nM	US-9464060: Compounds
4-[[2-cyclopropylethyl-[4-(2-fluorophenoxy)benzoyl]amino]methyl]benzoic acid	IC50	15 nM	US-9464060: Compounds
CHEMBL357053	EC50	15 nM
4-[[[4-(2-chloro-6-fluorophenoxy)benzoyl]-(cyclopropylmethyl)amino]methyl]benzoic acid	IC50	17 nM	US-9464060: Compounds
4-[[3-(3-fluorophenyl)propyl-[4-(2-methoxyphenoxy)cyclohexanecarbonyl]amino]methyl]benzoic acid	IC50	17 nM	US-9464060: Compounds
4-[[benzyl-[4-(2,6-dimethylphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	19 nM	US-9464060: Compounds
CHEMBL1222042	IC50	20 nM
4-[[[4-(2,6-dimethylphenoxy)benzoyl]-(2-phenylethyl)amino]methyl]benzoic acid	IC50	22 nM	US-9464060: Compounds
4-[[cyclobutylmethyl-[4-(2-fluorophenoxy)benzoyl]amino]methyl]benzoic acid	IC50	24 nM	US-9464060: Compounds
4-[[[4-(2-chlorophenoxy)benzoyl]-(2-phenylethyl)amino]methyl]benzoic acid	IC50	24 nM	US-9464060: Compounds
CHEMBL153043	EC50	24 nM
4-[[cyclopropylmethyl-[4-(2,6-difluorophenoxy)benzoyl]amino]methyl]benzoic acid	IC50	25 nM	US-9464060: Compounds
CHEMBL2335049	EC50	26 nM
4-[[cyclopropylmethyl-[2-fluoro-4-(2-fluorophenoxy)benzoyl]amino]methyl]benzoic acid	IC50	27 nM	US-9464060: Compounds
4-[[[4-(2-chlorophenoxy)benzoyl]-(2,2,2-trifluoroethyl)amino]methyl]benzoic acid	IC50	29 nM	US-9464060: Compounds
4-[[cyclopropylmethyl-[4-(2-methylphenoxy)benzoyl]amino]methyl]benzoic acid	IC50	30 nM	US-9464060: Compounds
CHEMBL5290794	IC50	30 nM
4-[[[4-(2-fluorophenoxy)benzoyl]-[(3-methoxycyclobutyl)methyl]amino]methyl]benzoic acid	IC50	31 nM	US-10100018: Amide derivatives as lysophosphatidic acid receptor antagonists

ChEMBL bioactivities

176 potent at pChembl≥5 of 176 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.59	EC50	0.26	nM	CHEMBL2335049
9.59	EC50	0.257	nM	CHEMBL2335049
9.40	IC50	0.4	nM	CHEMBL3936755
9.40	IC50	0.4	nM	CHEMBL3966526
9.08	EC50	0.83	nM	CHEMBL2335052
9.08	EC50	0.8318	nM	CHEMBL2335052
9.00	IC50	1	nM	CHEMBL3972698
9.00	IC50	1	nM	CHEMBL3943133
8.74	EC50	1.81	nM	CHEMBL2335051
8.74	EC50	1.82	nM	CHEMBL2335051
8.70	IC50	2	nM	CHEMBL3911605
8.70	IC50	2	nM	CHEMBL3980736
8.52	EC50	3	nM	CHEMBL2335050
8.52	EC50	3.02	nM	CHEMBL2335050
8.52	IC50	3	nM	CHEMBL3900559
8.47	EC50	3.4	nM	CHEMBL2335047
8.47	EC50	3.388	nM	CHEMBL2335047
8.40	IC50	4	nM	CHEMBL3920849
8.30	EC50	5.012	nM	CHEMBL357053
8.30	IC50	5	nM	CHEMBL3945517
8.30	IC50	5	nM	CHEMBL3910049
8.30	IC50	5	nM	CHEMBL3980174
8.29	EC50	5.1	nM	CHEMBL357053
8.22	IC50	6	nM	CHEMBL3891550
8.22	IC50	6	nM	CHEMBL3920145
8.21	EC50	6.1	nM	CHEMBL2335048
8.21	EC50	6.166	nM	CHEMBL2335048
8.20	EC50	6.3	nM	CHEMBL2017139
8.20	EC50	6.31	nM	CHEMBL2017139
8.15	IC50	7	nM	CHEMBL3942894
8.15	IC50	7	nM	CHEMBL3951978
8.15	IC50	7	nM	CHEMBL3987061
8.10	IC50	8	nM	CHEMBL3901720
8.10	IC50	8	nM	CHEMBL3985179
8.09	EC50	8.2	nM	CHEMBL153043
8.09	EC50	8.128	nM	CHEMBL153043
8.05	IC50	9	nM	CHEMBL3910281
8.05	IC50	9	nM	CHEMBL3955284
8.05	IC50	9	nM	CHEMBL3961765
8.00	IC50	10	nM	CHEMBL3892760
8.00	IC50	10	nM	CHEMBL3918970
7.96	IC50	11	nM	CHEMBL3956413
7.96	IC50	11	nM	CHEMBL3918468
7.96	IC50	11	nM	CHEMBL3914963
7.96	IC50	11	nM	CHEMBL3911962
7.92	IC50	12	nM	CHEMBL3942192
7.92	EC50	12	nM	LYSOPHOSPHATIDIC ACID
7.82	IC50	15	nM	CHEMBL3914942
7.82	EC50	15	nM	CHEMBL5416462
7.80	IC50	16	nM	CHEMBL3986752

PubChem BioAssay actives

93 with measured affinity, of 339 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
sodium (2-hexadecoxy-3-methoxypropoxy)-hydroxy-oxido-sulfanylidene-lambda5-phosphane	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0003	uM
dihydroxy-(2-methoxy-3-octadecoxypropoxy)-sulfanylidene-lambda5-phosphane	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0008	uM
sodium [1-[hydroxy(oxido)phosphinothioyl]oxy-3-methoxypropan-2-yl] octadecanoate	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0018	uM
sodium (2-heptadecoxy-3-methoxypropoxy)-hydroxy-oxido-sulfanylidene-lambda5-phosphane	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0030	uM
dihydroxy-[(2S)-2-methoxy-3-octadecoxypropoxy]-sulfanylidene-lambda5-phosphane	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0034	uM
[(2S)-3-dihydroxyphosphinothioyloxy-2-methoxypropyl] octadecanoate	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0050	uM
dihydroxy-[(2R)-2-methoxy-3-octadecoxypropoxy]-sulfanylidene-lambda5-phosphane	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0061	uM
(3-dihydroxyphosphinothioyloxy-2-methoxypropyl) octadecanoate	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0063	uM
[(2R)-3-dihydroxyphosphinothioyloxy-2-methoxypropyl] octadecanoate	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0081	uM
[(2R)-2-hydroxy-3-phosphonooxypropyl] (Z)-octadec-9-enoate	457518: Agonist activity at LPA5 expressed in human chem1 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.0120	uM
[(2R)-3-hexadecoxy-2-hydroxypropyl] dihydrogen phosphate	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ec50	0.0150	uM
4-[[[2-[[1-(2,4-dichlorophenyl)-4-methyl-5-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methoxy]-2-methylpropanoyl]amino]methyl]benzoic acid	1938510: Antagonist activity at human LPA5 receptor by FLIPR analysis	ic50	0.0300	uM
4-(4-ethynylpiperidine-1-carbonyl)-6,7-dimethoxy-2-(3-methyl-1-benzothiophen-5-yl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0320	uM
6,7-dimethoxy-2-(3-methyl-1-benzothiophen-5-yl)-4-(piperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0320	uM
6,7-dimethoxy-2-(5-methyl-1,2-benzoxazol-3-yl)-4-(piperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0360	uM
2-[3-(dimethylamino)phenyl]-4-(4-ethynylpiperidine-1-carbonyl)-6,7-dimethoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0460	uM
6,7-dimethoxy-2-(3-methyl-1-benzofuran-5-yl)-4-(piperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0480	uM
2-(1-ethyl-2,3-dihydroindol-6-yl)-4-(4-fluoropiperidine-1-carbonyl)-6,7-dimethoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0580	uM
6,7-dimethoxy-4-(piperidine-1-carbonyl)-2-(3-propan-2-ylphenyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0630	uM
6,7-dimethoxy-2-(1-methylindol-6-yl)-4-(piperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0640	uM
[(2R)-2-hydroxy-3-phosphonooxypropyl] hexadecanoate	733688: Agonist activity at human LPA5 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0676	uM
4-(4-fluoropiperidine-1-carbonyl)-6,7-dimethoxy-2-(3-methyl-1-benzothiophen-5-yl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0690	uM
2-[3-(dimethylamino)phenyl]-4-(4-fluoropiperidine-1-carbonyl)-6,7-dimethoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0790	uM
2-[3-(dimethylamino)phenyl]-6,7-dimethoxy-4-(piperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0870	uM
2-[3-(dimethylamino)phenyl]-6,7-dimethoxy-4-(4-prop-1-ynylpiperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.0910	uM
1-[2-[3-(dimethylamino)phenyl]-6,7-dimethoxy-1-oxoisoquinoline-4-carbonyl]piperidine-4-carbonitrile	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.1020	uM
(2-hydroxy-3-phosphonooxypropyl) (Z)-octadec-9-enoate	1431881: Agonist activity at FLAG-tagged LPA5 receptor (unknown origin) expressed in rat B103 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	0.1400	uM
4-(4-fluoropiperidine-1-carbonyl)-6,7-dimethoxy-2-(3-methyl-1-benzofuran-5-yl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.1440	uM
2-[3-(dimethylamino)phenyl]-6,7-dimethoxy-4-(4-methylpiperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.1600	uM
2-(3-tert-butylphenyl)-6,7-dimethoxy-4-(piperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.1730	uM
4-(4-fluoropiperidine-1-carbonyl)-6,7-dimethoxy-2-(3-propan-2-ylphenyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.2000	uM
6,7-dimethoxy-2-(8-methylnaphthalen-2-yl)-4-(piperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.2100	uM
2-[3-(dimethylamino)phenyl]-4-(4-fluoropiperidine-1-carbonyl)-7-methoxy-6-pentoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.2300	uM
4-(8-azabicyclo[3.2.1]octane-8-carbonyl)-2-[3-(dimethylamino)phenyl]-6,7-dimethoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.2300	uM
2-[3-(dimethylamino)phenyl]-6,7-dimethoxy-4-(3-methylpiperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.2600	uM
2-[3-(4-nitrophenoxy)phenyl]-1,3-dioxoisoindole-5-carboxylic acid	454070: Binding affinity to LPA5	ki	0.2920	uM
4-(azocane-1-carbonyl)-2-[3-(dimethylamino)phenyl]-6,7-dimethoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.3010	uM
2-[3-(dimethylamino)phenyl]-N,6,7-trimethoxy-N-methyl-1-oxoisoquinoline-4-carboxamide	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.3200	uM
2-[3-(dimethylamino)phenyl]-4-(4-fluoropiperidine-1-carbonyl)-7-methoxy-6-propan-2-yloxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.3690	uM
2-[3-(dimethylamino)phenyl]-4-(4-fluoropiperidine-1-carbonyl)-7-methoxy-6-propoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.4800	uM
6-cyclohexyloxy-2-[3-(dimethylamino)phenyl]-4-(4-fluoropiperidine-1-carbonyl)-7-methoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.5100	uM
6,7-dimethoxy-4-(piperidine-1-carbonyl)-2-(3-propan-2-yloxyphenyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.6300	uM
2-[3-(dimethylamino)phenyl]-6,7-dimethoxy-4-(4-methoxypiperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.6400	uM
2-(1-benzothiophen-5-yl)-6,7-dimethoxy-4-(piperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.6400	uM
5-(3-chloro-4-cyclohexylphenyl)-1-(3-methoxyphenyl)pyrazole-3-carboxylic acid	2120490: Antagonist activity at LPA5 (unknown origin)	ic50	0.8000	uM
6-cyclopentyloxy-2-[3-(dimethylamino)phenyl]-4-(4-fluoropiperidine-1-carbonyl)-7-methoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.8900	uM
2-[3-(dimethylamino)phenyl]-6,7-dimethoxy-4-(2-methylpiperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	0.9900	uM
2-[3-(dimethylamino)phenyl]-4-(4-fluoropiperidine-1-carbonyl)-7-methoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	1.0600	uM
2-[3-(dimethylamino)phenyl]-4-(4,4-dimethylpiperidine-1-carbonyl)-6,7-dimethoxyisoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	1.1000	uM
2-(1-benzofuran-5-yl)-6,7-dimethoxy-4-(piperidine-1-carbonyl)isoquinolin-1-one	2000970: Antagonist activity at human LPA5 receptor expressed in RH7777 cells assessed as inhibition of EC80 concentration of hexadecyl LPA-induced calcium mobilization incubated for 15 mins by FLIPR method	ic50	1.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	5
Benzo(a)pyrene	affects methylation, decreases methylation	2
triphenyl phosphate	affects expression	1
quercitrin	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
lysophosphatidic acid	affects binding, decreases reaction, increases activity	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	decreases expression	1
ormosil	affects binding, decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
asparanin A	increases expression	1
Leflunomide	increases expression	1
Vehicle Emissions	decreases methylation	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Polyethylene Glycols	affects binding, decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	increases expression	1

ChEMBL screening assays

38 unique, capped per target: 29 functional, 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1064666	Functional	Antagonist activity at LPA5 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*
CHEMBL1064671	Binding	Binding affinity to LPA5	Structure-based drug design identifies novel LPA3 antagonists. — *Bioorg Med Chem*

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7TS	Ubigene A-549 LPAR5 KO	Cancer cell line	Male
CVCL_D8PE	Ubigene HCT 116 LPAR5 KO	Cancer cell line	Male
CVCL_E0GN	Ubigene HeLa LPAR5 KO	Cancer cell line	Female
CVCL_KX78	PathHunter CHO-K1 GPR92 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZK35	Tango GPR92-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 LPAR5 across ~30M SureChEMBL compounds — explore on Sugi Predict.