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GPR68 (G protein-coupled receptor 68)

Written2008-12Yan Xu
Department of Obstetrics, Gynecology, Indiana University School of Medicine, 975 W. Walnut St IB355A, Indianapolis, IN 46202, USA

(Note : for Links provided by Atlas : click)


Other aliasGPR12A
LocusID (NCBI) 8111
Atlas_Id 40745
Location 14q32.11  [Link to chromosome band 14q32]
Location_base_pair Starts at and ends at bp from pter
  Picture from Entrez Gene.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DPY19L3 (19q13.11) / GPR68 (14q32.11)NUMB (14q24.2) / GPR68 (14q32.11)
Note GPR68 (OGR1) is a G protein-coupled receptor (GPCR), which share high homology with other three GPCRs (TDAG8, G2A and GPR4). OGR1, as well as TDAG8, G2A and GPR4, has been shown to be proton-sensing GPCRs. In particular, OGR1 has been shown to be a proton-sensing receptor in bone. OGR1 is expressed in osteoclasts and osteoblasts, where it mediates acid-induced signaling pathways via G(q/11) protein, phospholipase C, IP(3) formation, and subsequent Ca2+ release from thapsigargin-sensitive stores. Acidic pH has been shown to induce cyclooxygenase-2 (COX-2) induction and prostaglandin E2 (PGE2) production, resulting in stimulation of bone calcium release and osteoclastogenesis. OGR1 family receptors can also mediate effects of several phospholipids. However, whether the lipid regulation is specific to these receptors is still under debate.


Note GPR68 (OGR1) is a proton sensing receptor. Its physiological role need to be further investigated.
  Picture from Entrez Gene.
Description The open reading frame of GPR68 is encoded by a single exon (1095 bp) located at chromosome 14q31.
Transcription GPR68 transcripts of ~3.0 kb in human.


Description Size: 365 amino acids.
Expression GPR68 is expressed in blood; bone; brain; connective tissue; embryonic tissue; eye; heart, intestine; lung; pancreas; placenta; peripheral blood leukocyte, prostate; skin; stomach; thymus; uterus; chondrosarcoma; leukemia; normal; pancreatic cancer; small intestine, soft tissue/muscle tissue tumor; spleen, stomach tumor; testis, uterine tumor; embryo; fetus; adult.
Localisation Cell membrane
Function Osteoclastogenesis
Homology OGR1, GPR4, G2A, and TDAG8 share 40% to 50% homology with each other and seem to form a family of GPCRs. GPCRs form homo- and hetero-dimers or -oligomers. Although GPR4 and OGR1 share more than 50% homology, GPR4 forms strong homo- and hetero-dimers with LPA and S1P receptors, but OGR1 forms very weak homo-dimer and relatively weak hetero-dimers with other receptors.

Implicated in

Entity Prostate cancer
Note Down regulated in metastatic prostate cancer.
Oncogenesis OGR1 is down regulated in metastatic prostate cancer tissues and over-expression OGR1 in prostate cancer cells suppress tumor metastasis. Thus, OGR1 has been considered as a tumor metastasis suppressor genes for prostate cancer (Singh et al., 2007).


Sphingosylphosphorylcholine enhances calcium entry in thyroid FRO cells by a mechanism dependent on protein kinase C.
Afrasiabi E, Blom T, Ekokoski E, Tuominen RK, Tornquist K.
Cell Signal. 2006 Oct;18(10):1671-8.
PMID 16490345
Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue.
An S, Tsai C, Goetzl EJ.
FEBS Lett. 1995 Nov 13;375(1-2):121-4.
PMID 7498459
Metabolic Acidosis Increases Intracellular Calcium in Bone Cells Through Activation of the Proton Receptor OGR1.
Frick KK, Krieger NS, Nehrke K, Bushinsky DA.
J Bone Miner Res. 2008 Oct 10. [Epub ahead of print]
PMID 18847331
Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors.
Huang CW, Tzeng JN, Chen YJ, Tsai WF, Chen CC, Sun WH.
Mol Cell Neurosci. 2007 Oct;36(2):195-210.
PMID 17720533
Extracellular acidification elicits spatially and temporally distinct Ca2+ signals.
Huang WC, Swietach P, Vaughan-Jones RD, Ansorge O, Glitsch MD.
Curr Biol. 2008 May 20;18(10):781-5.
PMID 18485712
Two ligands for a GPCR, proton vs lysolipid.
Im DS.
Acta Pharmacol Sin. 2005 Dec;26(12):1435-41.
PMID 16297340
RGS18 acts as a negative regulator of osteoclastogenesis by modulating the acid-sensing OGR1/NFAT signaling pathway.
Iwai K, Koike M, Ohshima S, Miyatake K, Uchiyama Y, Saeki Y, Ishii M.
J Bone Miner Res. 2007 Oct;22(10):1612-20.
PMID 17576169
Novel clusters of receptors for sphingosine-1-phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: new receptors for "old" ligands.
Kostenis E.
J Cell Biochem. 2004 Aug 1;92(5):923-36.
PMID 15258916
Proton-sensing G-protein-coupled receptors.
Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H, Wolf RM, Seuwen K.
Nature. 2003 Sep 4;425(6953):93-8.
PMID 12955148
Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism.
Meyer zu Heringdorf D, Jakobs KH.
Biochim Biophys Acta. 2007 Apr;1768(4):923-40.
PMID 17078925
Sphingosylphosphorylcholine antagonizes proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1)-mediated inositol phosphate production and cAMP accumulation.
Mogi C, Tomura H, Tobo M, Wang JQ, Damirin A, Kon J, Komachi M, Hashimoto K, Sato K, Okajima F.
J Pharmacol Sci. 2005 Oct;99(2):160-7.
PMID 16210776
Extracellular acidification enhances osteoclast survival through an NFAT-independent, protein kinase C-dependent pathway.
Pereverzev A, Komarova SV, Korcok J, Armstrong S, Tremblay GB, Dixon SJ, Sims SM.
Bone. 2008 Jan;42(1):150-61.
PMID 17964236
Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells.
Radu CG, Nijagal A, McLaughlin J, Wang L, Witte ON.
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1632-7.
PMID 15665078
Receptors for protons or lipid messengers or both?
Seuwen K, Ludwig MG, Wolf RM.
J Recept Signal Transduct Res. 2006;26(5-6):599-610.
PMID 17118800
Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer.
Singh LS, Berk M, Oates R, Zhao Z, Tan H, Jiang Y, Zhou A, Kirmani K, Steinmetz R, Lindner D, Xu Y.
J Natl Cancer Inst. 2007 Sep 5;99(17):1313-27.
PMID 17728215
Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors.
Tomura H, Mogi C, Sato K, Okajima F.
Cell Signal. 2005 Dec;17(12):1466-76.
PMID 16014326
Cyclooxygenase-2 expression and prostaglandin E2 production in response to acidic pH through OGR1 in a human osteoblastic cell line.
Tomura H, Wang JQ, Liu JP, Komachi M, Damirin A, Mogi C, Tobo M, Nochi H, Tamoto K, Im DS, Sato K, Okajima F.
J Bone Miner Res. 2008 Jul;23(7):1129-39.
PMID 18302504
Identification of human OGR1, a novel G protein-coupled receptor that maps to chromosome 14.
Xu Y, Casey G.
Genomics. 1996 Jul 15;35(2):397-402.
PMID 8661159
Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1) during osteoclastogenesis.
Yang M, Mailhot G, Birnbaum MJ, MacKay CA, Mason-Savas A, Odgren PR.
J Biol Chem. 2006 Aug 18;281(33):23598-605.
PMID 16787916
Homo- and hetero-dimerization of LPA/S1P receptors, OGR1 and GPR4.
Zaslavsky A, Singh LS, Tan H, Ding H, Liang Z, Xu Y.
Biochim Biophys Acta. 2006 Oct;1761(10):1200-12.
PMID 17023202


This paper should be referenced as such :
Xu, Y
GPR68 (G protein-coupled receptor 68)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(11):845-846.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(14;14)(q24;q32) NUMB/GPR68
t(14;19)(q32;q13) DPY19L3/GPR68

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)8111
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 18 17:37:59 CEST 2018

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