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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LPAR4
lysophosphatidic acid receptor 4
Chromosome X · Xq21.1
NCBI Gene: 2846Ensembl: ENSG00000147145.15HGNC: HGNC:4478UniProt: Q99677
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneprotein bindingG protein-coupled receptor signaling pathwaylysophosphatidic acid receptor activityneurodegenerative diseaseGraves diseaseneoplasmuridine-cytidineuria
✦AI Summary

LPAR4 is a G protein-coupled receptor for lysophosphatidic acid (LPA) that transduces signals through increased intracellular calcium and adenylyl cyclase activation. In cancer biology, LPAR4 is stress-responsive and plays a critical role in tumor initiation; pancreatic cancer cells upregulate LPAR4 in response to isolation stress or chemotherapy via downregulation of miR-139-5p, promoting drug resistance and self-renewal through an LPAR4/AKT/CREB axis that enhances fibronectin production 1. In cardiac development, SOX17-mediated LPAR4 expression is essential during pluripotent stem cell-derived cardiac differentiation and cardiac regeneration following myocardial infarction; p38 MAPK inhibition of LPAR4 signaling early after MI improves cardiac repair and reduces fibrotic scarring 2. LPAR4 regulates bone homeostasis by suppressing osteogenic and promoting adipogenic differentiation of mesenchymal progenitor cells through inactivation of RhoA/ROCK1/β-catenin signaling 3. In tissue fibrosis, miR-139-5p targeting of LPAR4 inhibits epithelial-mesenchymal transition via PI3K/Akt suppression 4. LPAR4 is significantly upregulated in pancreatic ductal adenocarcinoma tumor fibroblasts 5 and ovarian endometriotic cysts 6, where it acts as a key mediator of pathological LPA signaling. These findings establish LPAR4 as a versatile therapeutic target across cancer, cardiac disease, bone metabolism, and fibrotic pathologies.

Sources cited
1
LPAR4 upregulation in pancreatic cancer cells promotes stress tolerance, drug resistance, and tumor initiation through fibronectin production via LPAR4/AKT/CREB axis
PMID: 36646789
2
SOX17-mediated LPAR4 expression is essential during cardiac development and regeneration; p38 MAPK inhibition of LPAR4 improves cardiac repair after myocardial infarction
PMID: 37394586
3
LPAR4 inhibits osteogenic and promotes adipogenic differentiation of mesenchymal progenitor cells through inactivation of RhoA/ROCK1/β-catenin signaling
PMID: 31778241
4
miR-139-5p targets LPAR4 to inhibit epithelial-mesenchymal transition and fibrosis through PI3K/Akt pathway suppression
PMID: 29240250
5
LPAR4 expression is significantly elevated in pancreatic ductal adenocarcinoma tumor fibroblasts
PMID: 39267662
6
LPAR2 and LPAR4 are the main receptors responsible for LPA actions in ovarian endometriotic cysts, with high expression correlating with hormone receptors
PMID: 29621954
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
Graves diseaseOpen Targets
0.28Weak
neoplasmOpen Targets
0.08Suggestive
uridine-cytidineuriaOpen Targets
0.06Suggestive
isolated sedoheptulokinase deficiencyOpen Targets
0.06Suggestive
pentosuriaOpen Targets
0.06Suggestive
Idiopathic hypercalciuriaOpen Targets
0.06Suggestive
medullary sponge kidneyOpen Targets
0.05Suggestive
congenital adrenal hyperplasiaOpen Targets
0.04Suggestive
congenital lipoid adrenal hyperplasia due to STAR deficencyOpen Targets
0.04Suggestive
primary hyperoxaluria type 2Open Targets
0.04Suggestive
myocardial infarctionOpen Targets
0.04Suggestive
proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosisOpen Targets
0.04Suggestive
Dent diseaseOpen Targets
0.04Suggestive
Dent disease type 1Open Targets
0.04Suggestive
childhood supratentorial ependymomaOpen Targets
0.03Suggestive
adenomyosisOpen Targets
0.03Suggestive
thyroid diseaseOpen Targets
0.03Suggestive
rheumatoid arthritisOpen Targets
0.02Suggestive
atherosclerosisOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GNA13Protein interaction99%F2RProtein interaction97%GNA12Protein interaction97%AGTProtein interaction97%CHRM1Protein interaction97%GNAQProtein interaction97%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
57%
Heart
43%
Brain
26%
Lung
2%
Liver
0%
Gene Interaction Network
Click a node to explore
LPAR4GNA13F2RGNA12AGTCHRM1GNAQ
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q99677
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
2.37LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.51 [1.00–2.37]
RankingsWhere LPAR4 stands among ~20K protein-coding genes
  • #12,380of 20,598
    Most Researched28
  • #17,857of 17,882
    Most Constrained (LOEUF)2.37
Genes detectedLPAR4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Pancreatic cancer cells upregulate LPAR4 in response to isolation stress to promote an ECM-enriched niche and support tumour initiation.
PMID: 36646789
Nat Cell Biol · 2023
1.00
2
SOX17-mediated LPAR4 expression plays a pivotal role in cardiac development and regeneration after myocardial infarction.
PMID: 37394586
Exp Mol Med · 2023
0.90
3
Lysophosphatidic acid receptor 4 regulates osteogenic and adipogenic differentiation of progenitor cells via inactivation of RhoA/ROCK1/β-catenin signaling.
PMID: 31778241
Stem Cells · 2020
0.80
4
LPAR4 establishes a tumour-initiating niche.
PMID: 36646790
Nat Cell Biol · 2023
0.70
5
Inhibitory effects of β-galactoside α2,6-sialyltransferase 1 on the Hippo pathway in breast cancer cells.
PMID: 40409546
J Biol Chem · 2025
0.60