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LPA6 receptor

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Target not currently curated in GtoImmuPdb

Target id: 163

Nomenclature: LPA6 receptor

Family: Lysophospholipid (LPA) receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 344 13q14.2 LPAR6 lysophosphatidic acid receptor 6 11,15
Mouse 7 344 14 D3 Lpar6 lysophosphatidic acid receptor 6
Rat 7 344 15q11 Lpar6 lysophosphatidic acid receptor 6
Previous and Unofficial Names Click here for help
P2RY5 | LPA receptor 6 | oleoyl-L-alpha-lysophosphatidic acid receptor | P2Y purinoceptor 5 | purinergic receptor 5
Database Links Click here for help
Specialist databases
GPCRdb lpar6_human (Hs), lpar6_mouse (Mm), lpar6_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Zebrafish LPA6 receptor crystal structure
Resolution:  3.2Å
Species:  None
References:  17
Natural/Endogenous Ligands Click here for help

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LPA Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 6.0 pEC50 11,21
pEC50 6.0 [11,21]
LPA Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Mm Partial agonist 6.0 pEC50 21
pEC50 6.0 (EC50 1x10-6 M) [21]
View species-specific agonist tables
Agonist Comments
LPA6 was originally reported to bind extracellular nucleotides as ligands [20], although this was not substantiated by additional experiments [6,19].

Alkyl OMPT had similar agonist activity as 1-oleoyl LPA [21].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Gi/Go family
G12/G13 family
Adenylyl cyclase stimulation
Phospholipase C stimulation
Other - See Comments
Comments:  Increased intracellular calcium using a promiscuous Gs protein, ERK1/2 activation, and reduced forskolin-stimulated cAMP. G13-Rho pathway [21], and Gα12/13-Rho, PLC, PKC, ROCK, p38, PI3K pathway stimulation [5].
References:  5,11,21
Tissue Distribution Click here for help
Hair cells (follicles: skin, scalp, eyebrow), leukocytes
Expression level:  High
Species:  Human
Technique:  Protein blot, PCR, immunofluorescence
References:  10-12
Expression level:  High
Species:  Human
Technique:  Protein blot, PCR, immunofluorescence
References:  11
Spleen, thymus, leukocyte, prostate, ovary, testis, small intestine, colon, pancreas, placenta, liver, lung, heart, brain, skeletal muscle, kidney, keratinocytes
Species:  Human
Technique:  RT-PCR
References:  11
Human umbilical vein endothelial (HUVEC) cells
Species:  Human
Technique:  qRT-PCR
References:  22
Duodenum mucosa, jejunum mucosa, ileum mucosa, colon mucosa
Expression level:  High
Species:  Mouse
Technique:  Semiquantitative RT-PCR, Western immunoblotting
References:  5
Kidney, uterus, spleen, ileum, liver, skin, brain, heart, adrenal, lung
Species:  Mouse
Technique:  Northern blot
References:  11
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Cell permeability
Species:  Rat
Tissue:  Brain endothelial cells
Response measured:  Increased cell permeability in RBECs after LPA exposure
References:  8
Neurite retraction
Species:  Rat
Tissue:  Neuroblastoma
Response measured:  Increased neurite retraction in B103-p2y5 cells after LPA exposure
References:  21
Membrane blebbing
Species:  Rat
Tissue:  Liver
Response measured:  Increased membrane blebbing in RH7777-p2y5 hepatoma cells after LPA exposure
References:  21
Increased intracellular calcium when LPA6 was co-expressed with a promiscuous Gs protein, reduced forskolin-stimulated [cAMP]I, and ERK1/2 activation
Species:  Mouse
Tissue:  Liver
Response measured:  Increased intracellular calcium, reduced forskolin-stimulated [cAMP]I, and ERK1/2 activation
References:  21
Stress fiber formation.
Species:  Human
Tissue:  Umbilical vein endothelial cells.
Response measured:  Increased actin stress fiber formation upon LPA stimulation.
References:  22
Physiological Functions Click here for help
Hair growth
Species:  Human
Tissue:  Hair follicles (skin, scalp, eyebrow)
References:  3,10-11,14
Vascular stability.
Species:  Human
Tissue:  Umbilical vein endothelial cells (HUVECs)
References:  22
Physiological Consequences of Altering Gene Expression Click here for help
LPA6 KO mice have abnormal vasculature and impaired vascular activities
Species:  Mouse
Tissue:  Whole animal
Technique:  Gene knockout
References:  4
LPA6-KO mice have accelerated developmental maturation of oligodendrocytes.
Species:  Mouse
Technique:  Gene knockout
References:  16
LPA-induced hypertensive response was blocked in LPA4 and LPA6 KO mice.
Species:  Mouse
Tissue:  Brain
Technique:  Gene knockout
References:  4
Physiological Consequences of Altering Gene Expression Comments
Lpar6 knockout mice have not yet been characterized, but are expected to have hypotrichosis/woolly hair.
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Hypotrichosis 8; HYPT8
Synonyms: Hypotrichosis [Disease Ontology: DOID:4535]
Hypotrichosis simplex [Orphanet: ORPHA55654]
Woolly hair [Orphanet: ORPHA170]
Disease Ontology: DOID:4535
OMIM: 278150
Orphanet: ORPHA55654, ORPHA170
References:  3,9-11,14
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human - Deletion of entire LPAR6 gene 7
Frameshift: Deletion Human c.472delC One base pair deletion that leads to frameshift and premature stop, resulting in a truncated protein. 10
Frameshift: Duplication Human c.64_67dupTGCA 4 base pair duplication that leads to frameshift and premature stop codon, resulting in a truncated protein. 10
Frameshift: Insertion Human 24insHfsX52 c.69insCATG Insertion of 4-nucleotide base 1,15,18
Frameshift: Insertion Human I194FfsX11 Insertion in a stretch of T at position 577 to 583 lead to substitution of isoleucine to phenylalanine at amino acid position 194 and a frameshift leading to a premature stop 2
Missense Human D63V c.188A>T Amino acid substitution of acidic polar aspartate to nonpolar valine 1,14,18
Missense Human G146R c.436G>A Amino acid substitution of nonpolar glycine to polar arginine 1-2,18
Missense Human I188F c.562A>T Amino acid substitution of nonpolar isoleucine to nonpolar phenylalanine 15,18
Missense Human N248Y c.742A>T Amino acid subsitution of a polar uncharged (neutral) asparagine with an aromatic hydrophobic nonpolar tyrosine 18
Missense Human L277P c.830C>T Amino acid substitution of nonpolar hydrophobic leucine with cyclic proline 18
Missense Human C278Y c.833G>A Amino acid substitution of nonpolar cysteine to polar tyrosine 13
Clinically-Relevant Mutations and Pathophysiology Comments
Other distinct missense mutations include E189K [15], as well as deletion (c.172-175delAACT; 177delG; p.N58-L59delinsCfsX88) [18].


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1. Azeem Z, Jelani M, Naz G, Tariq M, Wasif N, Kamran-Ul-Hassan Naqvi S, Ayub M, Yasinzai M, Amin-Ud-Din M, Wali A et al.. (2008) Novel mutations in G protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3). Hum Genet, 123 (5): 515-9. [PMID:18461368]

2. Azhar A, Tariq M, Baig SM, Dahl N, Klar J. (2012) A novel mutation in lysophosphatidic acid receptor 6 gene in autosomal recessive hypotrichosis and evidence for a founder effect. Eur J Dermatol, 22 (4): 464-6. [PMID:22531990]

3. Horev L, Saad-Edin B, Ingber A, Zlotogorski A. (2010) A novel deletion mutation in P2RY5/LPA(6) gene cause autosomal recessive woolly hair with hypotrichosis. J Eur Acad Dermatol Venereol, 24 (7): 858-9. [PMID:20015179]

4. Kano K, Matsumoto H, Inoue A, Yukiura H, Kanai M, Chun J, Ishii S, Shimizu T, Aoki J. (2019) Molecular mechanism of lysophosphatidic acid-induced hypertensive response. Sci Rep, 9 (1): 2662. [PMID:30804442]

5. Lee M, Choi S, Halldén G, Yo SJ, Schichnes D, Aponte GW. (2009) P2Y5 is a G(alpha)i, G(alpha)12/13 G protein-coupled receptor activated by lysophosphatidic acid that reduces intestinal cell adhesion. Am J Physiol Gastrointest Liver Physiol, 297 (4): G641-54. [PMID:19679818]

6. Li Q, Schachter JB, Harden TK, Nicholas RA. (1997) The 6H1 orphan receptor, claimed to be the p2y5 receptor, does not mediate nucleotide-promoted second messenger responses. Biochem Biophys Res Commun, 236 (2): 455-60. [PMID:9240460]

7. Mahmoudi H, Tug E, Parlak AH, Atasoy HI, Ludwig M, Polat M, Pasternack SM, Betz RC. (2012) Identification of an Alu-mediated 12.2-kb deletion of the complete LPAR6 (P2RY5) gene in a Turkish family with hypotrichosis and woolly hair. Exp Dermatol, 21 (6): 469-71. [PMID:22621192]

8. Masago K, Kihara Y, Yanagida K, Hamano F, Nakagawa S, Niwa M, Shimizu T. (2018) Lysophosphatidic acid receptor, LPA6, regulates endothelial blood-brain barrier function: Implication for hepatic encephalopathy. Biochem Biophys Res Commun, 501 (4): 1048-1054. [PMID:29778535]

9. Nakamura M, Tokura Y. (2009) Congenital woolly hair without P2RY5 mutation. Dermatoendocrinol, 1 (1): 58-9. [PMID:20046591]

10. Pasternack SM, Murugusundram S, Eigelshoven S, Müller M, Kruse R, Lehmann P, Betz RC. (2009) Novel mutations in the P2RY5 gene in one Turkish and two Indian patients presenting with hypotrichosis and woolly hair. Arch Dermatol Res, 301 (8): 621-4. [PMID:19529952]

11. Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC. (2008) G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nat Genet, 40 (3): 329-34. [PMID:18297070]

12. Pasternack SM, von Kügelgen I, Müller M, Oji V, Traupe H, Sprecher E, Nöthen MM, Janecke AR, Betz RC. (2009) In vitro analysis of LIPH mutations causing hypotrichosis simplex: evidence confirming the role of lipase H and lysophosphatidic acid in hair growth. J Invest Dermatol, 129 (12): 2772-6. [PMID:19536142]

13. Petukhova L, Sousa Jr EC, Martinez-Mir A, Vitebsky A, Dos Santos LG, Shapiro L, Haynes C, Gordon D, Shimomura Y, Christiano AM. (2008) Genome-wide linkage analysis of an autosomal recessive hypotrichosis identifies a novel P2RY5 mutation. Genomics, 92 (5): 273-8. [PMID:18692127]

14. Shimomura Y, Garzon MC, Kristal L, Shapiro L, Christiano AM. (2009) Autosomal recessive woolly hair with hypotrichosis caused by a novel homozygous mutation in the P2RY5 gene. Exp Dermatol, 18 (3): 218-21. [PMID:18803659]

15. Shimomura Y, Wajid M, Ishii Y, Shapiro L, Petukhova L, Gordon D, Christiano AM. (2008) Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair. Nat Genet, 40 (3): 335-9. [PMID:18297072]

16. Spencer SA, Suárez-Pozos E, Soto-Verdugo J, Wang H, Afshari FS, Li G, Manam S, Yasuda D, Ortega A, Lister JA et al.. (2022) Lysophosphatidic acid signaling via LPA6 : A negative modulator of developmental oligodendrocyte maturation. J Neurochem, 163 (6): 478-499. [PMID:36153691]

17. Taniguchi R, Inoue A, Sayama M, Uwamizu A, Yamashita K, Hirata K, Yoshida M, Tanaka Y, Kato HE, Nakada-Nakura Y et al.. (2017) Structural insights into ligand recognition by the lysophosphatidic acid receptor LPA6. Nature, 548 (7667): 356-360. [PMID:28792932]

18. Tariq M, Ayub M, Jelani M, Basit S, Naz G, Wasif N, Raza SI, Naveed AK, ullah Khan S, Azeem Z et al.. (2009) Mutations in the P2RY5 gene underlie autosomal recessive hypotrichosis in 13 Pakistani families. Br J Dermatol, 160 (5): 1006-10. [PMID:19292720]

19. von Kügelgen I. (2006) Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol Ther, 110 (3): 415-32. [PMID:16257449]

20. Webb TE, Kaplan MG, Barnard EA. (1996) Identification of 6H1 as a P2Y purinoceptor: P2Y5. Biochem Biophys Res Commun, 219 (1): 105-10. [PMID:8619790]

21. Yanagida K, Masago K, Nakanishi H, Kihara Y, Hamano F, Tajima Y, Taguchi R, Shimizu T, Ishii S. (2009) Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6. J Biol Chem, 284 (26): 17731-41. [PMID:19386608]

22. Yukiura H, Kano K, Kise R, Inoue A, Aoki J. (2015) LPP3 localizes LPA6 signalling to non-contact sites in endothelial cells. J Cell Sci, 128 (21): 3871-7. [PMID:26345369]


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