LPAR4

Summary

LPAR4 (lysophosphatidic acid receptor 4, HGNC:4478) is a protein-coding gene on chromosome Xq21.1, encoding Lysophosphatidic acid receptor 4 (Q99677). Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities.

This gene encodes a member of the lysophosphatidic acid receptor family. It may also be related to the P2Y receptors, a family of receptors that bind purine and pyrimidine nucleotides and are coupled to G proteins. The encoded protein may play a role in monocytic differentiation.

Source: NCBI Gene 2846 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total
• GTEx eGene: eQTL in 18 tissues, sQTL in 0 (q < 0.05)
• MANE Select transcript: NM_001278000
• Notable: 52 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4478
Approved symbol	LPAR4
Name	lysophosphatidic acid receptor 4
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Aliases	P2Y9, P2Y5-LIKE, P2RY9, LPA4
Ensembl gene	ENSG00000147145
Ensembl biotype	protein_coding
OMIM	300086
Entrez	2846

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000614823

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 4: 2, TSL 5: 1

ENST00000614823, ENST00000435339, ENST00000514744, ENST00000610214, ENST00000885310, ENST00000919745, ENST00000919746, ENST00000919747, ENST00000919748, ENST00000919749, ENST00000919750, ENST00000919751, ENST00000919752, ENST00000919753, ENST00001136578

RefSeq mRNA: 2 — MANE Select: NM_001278000 NM_001278000, NM_005296

CCDS: CCDS14441

Canonical transcript exons

ENST00000614823 — 5 exons

Exon	Start	End
ENSE00002028757	78750174	78750223
ENSE00002050864	78751210	78751311
ENSE00003703680	78750730	78750792
ENSE00003742495	78754791	78758714
ENSE00003917663	78747720	78748034

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 99.91.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0640 / max 113.8635, expressed in 255 samples.

Highest expression (Bgee): sural nerve, buccal mucosa cell, tibia, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LPAR4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

18 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Aorta	eqtl	4.7e-10	-0.28	X:78507275:C:G
Cells Cultured fibroblasts	eqtl	4.1e-08	+0.19	X:79314583:T:A
Adipose Subcutaneous	eqtl	2.1e-07	+0.20	X:78852466:C:T
Artery Tibial	eqtl	2.1e-07	+0.19	X:78748513:G:A
Nerve Tibial	eqtl	4.3e-07	+0.21	X:78708417:A:C
Esophagus Muscularis	eqtl	2.3e-04	+0.18	X:78626913:T:C
Thyroid	eqtl	2.8e-04	+0.13	X:79263268:A:G
Colon Sigmoid	eqtl	6.5e-04	+0.24	X:79209244:G:A
Adipose Visceral Omentum	eqtl	1.5e-03	+0.15	X:78750791:A:G
Brain Cerebellum	eqtl	2.2e-03	+0.24	X:78728713:T:C
Heart Left Ventricle	eqtl	5.0e-03	+0.12	X:78350453:G:C
Heart Atrial Appendage	eqtl	7.5e-03	+0.14	X:78777531:C:T
Skin Not Sun Exposed Suprapubic	eqtl	9.2e-03	+0.15	X:78787239:C:T
Artery Coronary	eqtl	9.9e-03	+0.79	X:78713814:C:T
Testis	eqtl	1.0e-02	-0.58	X:78186990:G:A
Brain Cerebellar Hemisphere	eqtl	1.2e-02	-0.18	X:78695813:G:T
Minor Salivary Gland	eqtl	2.1e-02	-0.75	X:79209119:C:A
Brain Anterior cingulate cortex BA24	eqtl	3.2e-02	+1.22	X:78753210:C:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
196788	1.0640	255

Top tissues by expression

showing 100 of 284 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	99.91	gold quality
buccal mucosa cell	CL:0002336	98.89	gold quality
tibia	UBERON:0000979	95.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.71	gold quality
ventricular zone	UBERON:0003053	79.63	gold quality
cartilage tissue	UBERON:0002418	77.77	gold quality
ganglionic eminence	UBERON:0004023	77.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.59	gold quality
embryo	UBERON:0000922	70.08	gold quality
calcaneal tendon	UBERON:0003701	69.30	gold quality
tendon	UBERON:0000043	68.87	gold quality
tendon of biceps brachii	UBERON:0008188	68.47	silver quality
left ovary	UBERON:0002119	68.41	gold quality
ovary	UBERON:0000992	67.46	gold quality
monocyte	CL:0000576	67.42	gold quality
mononuclear cell	CL:0000842	67.04	gold quality
leukocyte	CL:0000738	67.00	gold quality
right ovary	UBERON:0002118	66.89	gold quality
cranial nerve II	UBERON:0000941	66.66	gold quality
mucosa of stomach	UBERON:0001199	65.53	gold quality
cortical plate	UBERON:0005343	63.56	gold quality
paraflocculus	UBERON:0005351	63.37	gold quality
endometrium epithelium	UBERON:0004811	62.94	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.85	gold quality
middle frontal gyrus	UBERON:0002702	62.76	silver quality
gall bladder	UBERON:0002110	61.34	gold quality
corpus callosum	UBERON:0002336	61.02	gold quality
apex of heart	UBERON:0002098	60.95	gold quality
smooth muscle tissue	UBERON:0001135	60.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	59.98	gold quality
lower esophagus	UBERON:0013473	59.89	gold quality
rectum	UBERON:0001052	59.67	gold quality
body of uterus	UBERON:0009853	59.66	gold quality
adrenal tissue	UBERON:0018303	59.29	gold quality
layer of synovial tissue	UBERON:0007616	59.24	silver quality
ascending aorta	UBERON:0001496	58.50	gold quality
amygdala	UBERON:0001876	58.32	gold quality
islet of Langerhans	UBERON:0000006	58.28	gold quality
thoracic aorta	UBERON:0001515	58.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	58.04	gold quality
primary visual cortex	UBERON:0002436	57.92	gold quality
descending thoracic aorta	UBERON:0002345	57.86	gold quality
omental fat pad	UBERON:0010414	57.52	gold quality
spinal cord	UBERON:0002240	57.49	gold quality
peritoneum	UBERON:0002358	57.47	gold quality
pigmented layer of retina	UBERON:0001782	57.29	silver quality
Ammon’s horn	UBERON:0001954	57.13	gold quality
left coronary artery	UBERON:0001626	56.95	gold quality
parietal pleura	UBERON:0002400	56.87	gold quality
adipose tissue of abdominal region	UBERON:0007808	56.80	gold quality
decidua	UBERON:0002450	56.55	gold quality
left uterine tube	UBERON:0001303	56.49	gold quality
right atrium auricular region	UBERON:0006631	56.09	gold quality
right coronary artery	UBERON:0001625	56.04	gold quality
coronary artery	UBERON:0001621	55.96	gold quality
pleura	UBERON:0000977	55.71	silver quality
cardiac atrium	UBERON:0002081	55.57	gold quality
cortex of kidney	UBERON:0001225	55.28	gold quality
aorta	UBERON:0000947	55.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	54.87	gold quality
caudate nucleus	UBERON:0001873	54.86	gold quality
female reproductive system	UBERON:0000474	54.76	gold quality
esophagus	UBERON:0001043	54.57	gold quality
occipital lobe	UBERON:0002021	54.56	gold quality
visceral pleura	UBERON:0002401	54.34	gold quality
heart	UBERON:0000948	54.10	gold quality
endometrium	UBERON:0001295	53.82	gold quality
trabecular bone tissue	UBERON:0002483	53.81	silver quality
cerebellar vermis	UBERON:0004720	53.78	gold quality
connective tissue	UBERON:0002384	53.62	gold quality
uterus	UBERON:0000995	53.44	gold quality
temporal lobe	UBERON:0001871	53.25	gold quality
adipose tissue	UBERON:0001013	53.11	gold quality
popliteal artery	UBERON:0002250	53.09	gold quality
tibial artery	UBERON:0007610	53.04	gold quality
hair follicle	UBERON:0002073	52.89	gold quality
muscle layer of sigmoid colon	UBERON:0035805	52.66	gold quality
choroid plexus epithelium	UBERON:0003911	52.52	silver quality
vermiform appendix	UBERON:0001154	52.40	gold quality
ectocervix	UBERON:0012249	52.07	gold quality
heart left ventricle	UBERON:0002084	51.62	gold quality
telencephalon	UBERON:0001893	51.51	gold quality
colonic epithelium	UBERON:0000397	51.32	gold quality
cardiac ventricle	UBERON:0002082	51.24	gold quality
quadriceps femoris	UBERON:0001377	51.17	gold quality
cerebral cortex	UBERON:0000956	51.13	gold quality
thymus	UBERON:0002370	51.07	gold quality
skin of hip	UBERON:0001554	51.05	silver quality
prefrontal cortex	UBERON:0000451	50.89	gold quality
uterine cervix	UBERON:0000002	50.88	gold quality
caecum	UBERON:0001153	50.81	gold quality
vastus lateralis	UBERON:0001379	50.80	gold quality
nucleus accumbens	UBERON:0001882	50.67	gold quality
putamen	UBERON:0001874	50.53	gold quality
vagina	UBERON:0000996	50.45	gold quality
sigmoid colon	UBERON:0001159	50.44	gold quality
forebrain	UBERON:0001890	50.41	gold quality
central nervous system	UBERON:0001017	50.32	gold quality
endocervix	UBERON:0000458	50.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.18

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Hippocampus	tissue	4.6
Ovary	tissue	3.1
Choroid plexus	tissue	1.8
Caudate putamen	tissue	1.3
Frontal cortex	tissue	1.2
Spinal cord	tissue	1.2
Skeletal muscle	tissue	1.0
Amygdala	tissue	1.0
Nucleus accumbens	tissue	1.0
Hypothalamus	tissue	1.0
Periaqueductal gray	tissue	1.0
Midbrain	tissue	0.9
Substantia nigra	tissue	0.9
Hippocampal formation	tissue	0.9
Septum	tissue	0.9
Pons	tissue	0.8
Medulla oblongata	tissue	0.8
Corpus callosum	tissue	0.8
Endometrium 1	tissue	0.7
Putamen	tissue	0.7
Thalamus	tissue	0.7
Breast	tissue	0.6
Heart muscle	tissue	0.6
Basal ganglia	tissue	0.6
Superior colliculi	tissue	0.6
Gallbladder	tissue	0.6
Locus coeruleus	tissue	0.6
Bone marrow	tissue	0.6
Ventral forebrain	tissue	0.6
Cervix	tissue	0.5
Skin 1	tissue	0.5
Prefrontal cortex	tissue	0.5
Cerebral cortex	tissue	0.5
Esophagus	tissue	0.5
Pancreas	tissue	0.5
Prostate	tissue	0.5
Thymus	tissue	0.5
Olfactory bulb	tissue	0.5
Retrosplenial cortex	tissue	0.5
Insular cortex	tissue	0.5
Adipose tissue	tissue	0.4
Salivary gland	tissue	0.4
Motor cortex	tissue	0.4
Postcentral gyrus	tissue	0.4
Entorhinal cortex	tissue	0.4
Retrosplenial and cingulate cortex	tissue	0.4
Temporal cortex	tissue	0.4
Retina	tissue	0.3
Seminal vesicle	tissue	0.3
Rectum	tissue	0.3
Smooth muscle	tissue	0.3
Colon	tissue	0.3
Tongue	tissue	0.3
Spleen	tissue	0.3
Tonsil	tissue	0.3
Somatosensory cortex	tissue	0.3
Occipital cortex	tissue	0.3
Testis	tissue	0.2
Vagina	tissue	0.2
Urinary bladder	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Corpus callosum, genu (white matter) (6.0), Corpus callosum, splenium (white matter) (5.0), Cervical spinal cord, central gray (3.9), Dentate gyrus (3.7), Dorsal funiculus (white matter) (3.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PITX2, RUNX2

miRNA regulators (miRDB)

Targeting LPAR4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 93 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-7856-5P	99.75	69.99	2901
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-2681-5P	99.75	67.64	1655
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-670-5P	99.67	69.94	1565

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000614823 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 10)

• identified as the fourth lysophosphatidic acid (LPA) receptor; shares only 20-24% amino acid identities with Edg-2/LPA1, Edg-4/LPA2, and Edg-7/LPA3, and phylogenetic analysis also shows that p2y9/GPR23 is far distant from the Edg family (PMID:12724320)
• 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)
• LPA4 gene mutation may play some role in the pathogenesis of colon cancer. (PMID:20890765)
• Our data suggest that LPA4 signaling potentially modulates malignant behavior of SQ-20B cells. (PMID:23467751)
• 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)
• Mutation in LPAR4 gene is associated with papillary thyroid carcinoma. (PMID:26941397)
• 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)
• Potential genetic biomarkers predict adverse pregnancy outcome during early and mid-pregnancy in women with systemic lupus erythematosus. (PMID:36465614)
• Pancreatic cancer cells upregulate LPAR4 in response to isolation stress to promote an ECM-enriched niche and support tumour initiation. (PMID:36646789)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lpar4	ENSDARG00000089824
mus_musculus	Lpar4	ENSMUSG00000049929
rattus_norvegicus	Lpar4	ENSRNOG00000002428

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), F2RL3 (ENSG00000127533), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), CYSLTR2 (ENSG00000152207), F2RL2 (ENSG00000164220), F2RL1 (ENSG00000164251), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), F2R (ENSG00000181104), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1925384) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 21 distinct phenotype terms.

Mouse phenotype (MP)	Records
absent mandible	1
abnormal systemic arterial blood pressure	1
lung hemorrhage	1
internal hemorrhage	1
abnormal embryo development	1
decreased embryo size	1
abnormal fluid regulation	1
skin edema	1
hemorrhage	1
omphalocele	1
abnormal pericyte morphology	1
vascular smooth muscle hypoplasia	1
lymphangiectasis	1
decreased fetal size	1
hemopericardium	1
pericardial effusion	1
abnormal cellular extravasation	1
decreased grip strength	1
prenatal lethality, incomplete penetrance	1
preweaning lethality, incomplete penetrance	1
abnormal skin vasculature morphology	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
Pan troglodytes	Q9BG77	100.0%	Diamond
Gallus gallus	P34996	99.7%	Diamond
Meleagris gallopavo	P49652	99.7%	Diamond
Chlorocebus aethiops	O18982	99.4%	Diamond
Macaca mulatta	O97663	99.4%	Diamond
Macaca nemestrina	P56412	99.4%	Diamond
Macaca fascicularis	Q9BDS7	98.9%	Diamond
Meriones unguiculatus	Q99PE3	98.8%	Diamond
Papio hamadryas	P56488	97.9%	Diamond
Bos taurus	P48042	96.8%	Diamond
Cavia porcellus	P59902	96.2%	Diamond
Capra hircus	Q9GK76	96.2%	Diamond
Sus scrofa	P50132	95.6%	Diamond
Cricetulus griseus	P58826	94.5%	Diamond
Canis lupus familiaris	P11613	93.4%	Diamond
Cricetulus longicaudatus	Q00991	89.5%	Diamond
Xenopus laevis	P35373	89.0%	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
MIR4328	ncRNA	100422932
P2RY10	protein-coding	27334
RTL3	protein-coding	203430

Protein

Protein identifiers

Lysophosphatidic acid receptor 4 — Q99677 (reviewed: Q99677)

Alternative names: G protein-coupled receptor 23, P2Y purinoceptor 9, P2Y5-like receptor, Purinergic receptor 9

All UniProt accessions (2): Q99677, V9GY74

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Transduces a signal by increasing the intracellular calcium ions and by stimulating adenylyl cyclase activity. The rank order of potency for agonists of this receptor is 1-oleoyl- > 1-stearoyl- > 1-palmitoyl- > 1-myristoyl- > 1-alkyl- > 1-alkenyl-LPA.

Subcellular location. Cell membrane.

Tissue specificity. High expression in ovary. Not detected in the brain regions thalamus, putamen, caudate, frontal cortex, pons, hypothalamus and hippocampus.

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

RefSeq proteins (2): NP_001264929, NP_005287 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (24 total): topological domain 8, transmembrane region 7, glycosylation site 4, sequence conflict 3, chain 1, disulfide bond 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99677-F1	82.68	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

Subcellular location (HPA, imaging): plasma membrane; nuclear bodies; vesicles

Antibody reliability (HPA): IH uncertain · IF supported

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	111–188

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	15, 24, 28, 183

Function

Pathways and Gene Ontology

Reactome pathways

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

8 pathways:

ID	Pathway	Evidence
R-HSA-416476	G alpha (q) signalling events	curated
R-HSA-417957	P2Y 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-418038	Nucleotide-like (purinergic) receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 139 (showing top): RORA1_01, REACTOME_P2Y_RECEPTORS, CHX10_01, MORF_RAD51L3, EVI1_05, MORF_CTSB, BLALOCK_ALZHEIMERS_DISEASE_UP, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, TGANTCA_AP1_C, PID_LYSOPHOSPHOLIPID_PATHWAY, CUI_TCF21_TARGETS_2_DN, MORF_ATF2, CTAWWWATA_RSRFC4_Q2, SAFFORD_T_LYMPHOCYTE_ANERGY, CAIRO_LIVER_DEVELOPMENT_UP

GO Biological Process (2): G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165)

GO Molecular Function (5): lysophosphatidic acid binding (GO:0035727), lysophosphatidic acid receptor activity (GO:0070915), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), lipid binding (GO:0008289)

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

Reactome top-level categories

6 top-level categories:

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

GO top-level categories

18 GO namespaces:

Category	Terms
binding	2
G protein-coupled receptor activity	1
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phospholipid binding	1
anion binding	1
carbohydrate derivative binding	1
lysophosphatidic acid binding	1
bioactive lipid receptor activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 16 of 458 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPAR4	LPAR3	Q9UBY5	881
LPAR4	LPAR2	Q9HBW0	881
LPAR4	LPAR1	P78351	880
LPAR4	GPR22	Q99680	874
LPAR4	ENPP2	Q13822	720
LPAR4	GDPD1	Q8N9F7	635
LPAR4	GDPD3	Q7L5L3	624
LPAR4	GNA12	Q03113	569
LPAR4	TRIP6	Q15654	491
LPAR4	SST	P01166	441
LPAR4	S1PR3	Q99500	434
LPAR4	S1PR2	O95136	430
LPAR4	S1PR4	O95977	425
LPAR4	S1PR5	Q9H228	405
LPAR4	GNAQ	P50148	390
LPAR4	PLPP3	O14495	390

IntAct

Human interaction partners of LPAR4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
POTEF	association	0.530	2
RAMP1	physical association	0.400	2
RAMP2	physical association	0.400	2
RAMP3	physical association	0.400	2

BioGRID (58 interactions; top human partners by supporting records): ACAD10 (Affinity Capture-MS; 2 records), ARHGEF40 (Affinity Capture-MS; 2 records), ATL3 (Affinity Capture-MS; 2 records), ATM (Affinity Capture-MS; 2 records), ATP2B2 (Affinity Capture-MS; 2 records), BTAF1 (Affinity Capture-MS; 2 records), CAND2 (Affinity Capture-MS; 2 records), CAV1 (Affinity Capture-MS; 2 records), EFR3A (Affinity Capture-MS; 2 records), FASTKD1 (Affinity Capture-MS; 2 records), KIAA1244 (Affinity Capture-MS; 2 records), LMBRD2 (Affinity Capture-MS; 2 records), MTX1 (Affinity Capture-MS; 2 records), NLRX1 (Affinity Capture-MS; 2 records), PDS5B (Affinity Capture-MS; 2 records)

SIGNOR signaling

9 signaling interactions:

A	Effect	B	Mechanism
LPAR4	“up-regulates activity”	GNAS	binding
LPAR4	“up-regulates activity”	GNAL	binding
LPAR4	“up-regulates activity”	GNAI1	binding
LPAR4	“up-regulates activity”	GNAI3	binding
LPAR4	“up-regulates activity”	GNAO1	binding
LPAR4	“up-regulates activity”	GNAZ	binding
LPAR4	“up-regulates activity”	GNAQ	binding
LPAR4	“up-regulates activity”	GNA14	binding
“lysophosphatidic acid”	“up-regulates activity”	LPAR4	“chemical activation”

Disease & clinical

Genetic variants

Variant evidence for LPAR4: 52 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 398):

Position(s)	Effect	Δscore	Sites
X:78754789–78754790	acceptor_loss	0.9600	6
X:78751312–78751313	donor_loss	0.9400	6
X:78751316	donor_loss	0.9400	3
X:78749084	donor_gain	0.9300
X:78751207	acceptor_gain	0.9300
X:78751315	donor_loss	0.9300
X:78747789	donor_gain	0.9200
X:78747788	donor_gain	0.9100
X:78751202	acceptor_loss	0.9100
X:78751208–78751209	acceptor_loss	0.9100	6

AlphaMissense

937 missense substitutions predicted likely pathogenic (of 2,455 scored), across 245 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
D85	8	0.989	0.996
D135	8	0.974	0.990
F189	8	0.954	0.996
D307	8	0.953	0.985
N57	8	0.945	0.992
F262	8	0.938	0.995
F106	8	0.937	0.980
F128	8	0.922	0.971
F258	8	0.920	0.990
F213	8	0.898	0.991
F88	8	0.892	0.964
F64	8	0.839	0.945
F94	8	0.766	0.921
C188	7	0.996	0.998
W104	7	0.994	0.999
C111	7	0.993	0.998
F192	7	0.984	0.997
W197	7	0.981	0.999
F118	7	0.968	0.990
W163	7	0.964	0.998

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Disease associations

OMIM: gene MIM:300086 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5968 (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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
LPA	Agonist	7.35	pKd
[1-bromo-(3S)-hydrox-4-(palmitoyloxy)butyl]phosphate	Antagonist	6.58	pIC50
farnesyl monophosphate	Antagonist	5.84	pIC50
farnesyl diphosphate	Antagonist	5.7	pIC50
AM966	Antagonist	5.1	pIC50

Binding affinities (BindingDB)

11 measured of 11 human assays (11 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL2335047	EC50	10 nM
CHEMBL2335050	EC50	11 nM
CHEMBL2335051	EC50	12 nM
CHEMBL357053	EC50	15 nM
CHEMBL1222042	IC50	20 nM
CHEMBL153043	EC50	24 nM
CHEMBL2335049	EC50	26 nM
CHEMBL2335048	EC50	31 nM
CHEMBL364797	EC50	71 nM
lysophosphatidic acid	IC50	442 nM
CHEMBL2017139	IC50	2420 nM

ChEMBL bioactivities

28 potent at pChembl≥5 of 30 total, top 28 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.62	EC50	2.4	nM	CHEMBL2335051
8.61	EC50	2.455	nM	CHEMBL2335051
8.57	EC50	2.7	nM	CHEMBL357053
8.57	EC50	2.692	nM	CHEMBL357053
8.48	EC50	3.3	nM	CHEMBL2017139
8.48	EC50	3.311	nM	CHEMBL2017139
8.46	EC50	3.5	nM	CHEMBL2335047
8.46	EC50	3.467	nM	CHEMBL2335047
8.42	EC50	3.8	nM	CHEMBL2335052
8.42	EC50	3.8	nM	CHEMBL2335049
8.42	EC50	3.802	nM	CHEMBL2335052
8.42	EC50	3.802	nM	CHEMBL2335049
8.35	EC50	4.5	nM	CHEMBL2335050
8.35	EC50	4.467	nM	CHEMBL2335050
8.31	EC50	4.9	nM	CHEMBL2335048
8.31	EC50	4.9	nM	CHEMBL153043
8.31	EC50	4.898	nM	CHEMBL2335048
8.31	EC50	4.898	nM	CHEMBL153043
8.09	EC50	8.1	nM	LYSOPHOSPHATIDIC ACID
8.09	EC50	8.128	nM	LYSOPHOSPHATIDIC ACID
7.08	EC50	84	nM	CHEMBL364797
7.08	EC50	83.18	nM	CHEMBL364797
6.77	Ki	170	nM	CHEMBL3621353
6.77	Ki	170	nM	CHEMBL3621354
6.58	IC50	266	nM	CHEMBL3621964
6.24	EC50	570	nM	CHEMBL1222042
5.70	EC50	2000	nM	CHEMBL5085657
5.20	IC50	6310	nM	CHEMBL256470

PubChem BioAssay actives

24 with measured affinity, of 77 total; 13 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 [1-[hydroxy(oxido)phosphinothioyl]oxy-3-methoxypropan-2-yl] octadecanoate	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0024	uM
[(2S)-3-dihydroxyphosphinothioyloxy-2-methoxypropyl] octadecanoate	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0027	uM
(3-dihydroxyphosphinothioyloxy-2-methoxypropyl) octadecanoate	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0033	uM
dihydroxy-[(2S)-2-methoxy-3-octadecoxypropoxy]-sulfanylidene-lambda5-phosphane	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0035	uM
dihydroxy-(2-methoxy-3-octadecoxypropoxy)-sulfanylidene-lambda5-phosphane	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0038	uM
sodium (2-hexadecoxy-3-methoxypropoxy)-hydroxy-oxido-sulfanylidene-lambda5-phosphane	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0038	uM
sodium (2-heptadecoxy-3-methoxypropoxy)-hydroxy-oxido-sulfanylidene-lambda5-phosphane	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0045	uM
[(2R)-3-dihydroxyphosphinothioyloxy-2-methoxypropyl] octadecanoate	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0049	uM
dihydroxy-[(2R)-2-methoxy-3-octadecoxypropoxy]-sulfanylidene-lambda5-phosphane	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0049	uM
[(2R)-2-hydroxy-3-phosphonooxypropyl] (Z)-octadec-9-enoate	733689: Agonist activity at human LPA4 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] hexadecanoate	733689: Agonist activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425	ec50	0.0832	uM
(2-hydroxy-3-phosphonooxypropyl) (Z)-octadec-9-enoate	1431880: Agonist activity at LPA4 receptor (unknown origin) expressed in CHO 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	0.5700	uM
N-[(2S)-1-[4-(3,4-dichlorophenyl)sulfonylpiperazin-1-yl]propan-2-yl]-7-methylthieno[3,2-d]pyrimidin-4-amine	2034263: Antagonist activity at human LPA4 receptor expressed in CHO cells assessed as inhibition of LPA-induced cAMP accumulation pretreated for 30 mins followed by LPA stimulation and measured after 1 hr	ic50	6.3096	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	6
trichostatin A	affects cotreatment, decreases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Copper	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Nickel	decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

21 unique, capped per target: 16 functional, 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1073936	Functional	Antagonist activity at LPA4 receptor expressed in CHO cells assessed as inhibition of LPA-induced intracellular calcium response	Structure-based drug design identifies novel LPA3 antagonists. — *Bioorg Med Chem*
CHEMBL2344987	Binding	Intrinsic activity at human LPA4 receptor transfected in HEK293 cells after 1 hr by TGFalpha shedding assay in presence of Ki16425 relative to LPA	Phosphorothioate analogs of sn-2 radyl lysophosphatidic acid (LPA): metabolically stabilized LPA receptor agonists. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KA78	CHO-K1/P2Y9/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KX51	PathHunter CHO-K1 GPR23 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZK34	Tango GPR23-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 LPAR4 across ~30M SureChEMBL compounds — explore on Sugi Predict.