Atlas of Genetics and Cytogenetics in Oncology and Haematology

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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)


Alias (NCBI)GPR12A
HGNC (Hugo) GPR68
HGNC Alias symbOGR1
LocusID (NCBI) 8111
Atlas_Id 40745
Location 14q32.11  [Link to chromosome band 14q32]
Location_base_pair Starts at 91232532 and ends at 91253880 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping GPR68.png]
  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 ]

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

HGNC (Hugo)GPR68   4519
Entrez_Gene (NCBI)GPR68    G protein-coupled receptor 68
AliasesAI2A6; GPR12A; OGR1
GeneCards (Weizmann)GPR68
Ensembl hg19 (Hinxton)ENSG00000119714 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000119714 [Gene_View]  ENSG00000119714 [Sequence]  chr14:91232532-91253880 [Contig_View]  GPR68 [Vega]
ICGC DataPortalENSG00000119714
TCGA cBioPortalGPR68
AceView (NCBI)GPR68
Genatlas (Paris)GPR68
SOURCE (Princeton)GPR68
Genetics Home Reference (NIH)GPR68
Genomic and cartography
GoldenPath hg38 (UCSC)GPR68  -     chr14:91232532-91253880 -  14q32.11   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)GPR68  -     14q32.11   [Description]    (hg19-Feb_2009)
GoldenPathGPR68 - 14q32.11 [CytoView hg19]  GPR68 - 14q32.11 [CytoView hg38]
genome Data Viewer NCBIGPR68 [Mapview hg19]  
OMIM601404   617217   
Gene and transcription
Genbank (Entrez)AY615372 BC067470 BC067471 BC067472 BC069592
RefSeq transcript (Entrez)NM_001177676 NM_001348437 NM_003485
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)GPR68
Alternative Splicing GalleryENSG00000119714
Gene ExpressionGPR68 [ NCBI-GEO ]   GPR68 [ EBI - ARRAY_EXPRESS ]   GPR68 [ SEEK ]   GPR68 [ MEM ]
Gene Expression Viewer (FireBrowse)GPR68 [ Firebrowse - Broad ]
GenevisibleExpression of GPR68 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8111
GTEX Portal (Tissue expression)GPR68
Human Protein AtlasENSG00000119714-GPR68 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15743   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ15743  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ15743
Splice isoforms : SwissVarQ15743
Domaine pattern : Prosite (Expaxy)G_PROTEIN_RECEP_F1_1 (PS00237)    G_PROTEIN_RECEP_F1_2 (PS50262)   
Domains : Interpro (EBI)GPCR_Rhodpsn    GPCR_Rhodpsn_7TM    OGR1_rcpt   
Domain families : Pfam (Sanger)7tm_1 (PF00001)   
Domain families : Pfam (NCBI)pfam00001   
Conserved Domain (NCBI)GPR68
Blocks (Seattle)GPR68
Human Protein Atlas [tissue]ENSG00000119714-GPR68 [tissue]
Peptide AtlasQ15743
IPIIPI00976873   IPI00019433   
Protein Interaction databases
IntAct (EBI)Q15743
Ontologies - Pathways
Ontology : AmiGOG protein-coupled receptor activity  plasma membrane  integral component of plasma membrane  inflammatory response  G protein-coupled receptor signaling pathway  positive regulation of insulin secretion involved in cellular response to glucose stimulus  negative regulation of monocyte differentiation  cellular response to pH  positive regulation of osteoclast development  
Ontology : EGO-EBIG protein-coupled receptor activity  plasma membrane  integral component of plasma membrane  inflammatory response  G protein-coupled receptor signaling pathway  positive regulation of insulin secretion involved in cellular response to glucose stimulus  negative regulation of monocyte differentiation  cellular response to pH  positive regulation of osteoclast development  
REACTOMEQ15743 [protein]
REACTOME PathwaysR-HSA-416476 [pathway]   
NDEx NetworkGPR68
Atlas of Cancer Signalling NetworkGPR68
Wikipedia pathwaysGPR68
Orthology - Evolution
GeneTree (enSembl)ENSG00000119714
Phylogenetic Trees/Animal Genes : TreeFamGPR68
Homologs : HomoloGeneGPR68
Homology/Alignments : Family Browser (UCSC)GPR68
Gene fusions - Rearrangements
Fusion : MitelmanDPY19L3/GPR68 [19q13.11/14q32.11]  
Fusion : MitelmanNUMB/GPR68 [14q24.2/14q32.11]  
Fusion PortalDPY19L3 19q13.11 GPR68 14q32.11 SKCM
Fusion PortalNUMB 14q24.2 GPR68 14q32.11 LUSC
Fusion : Fusion_HubDPY19L3--GPR68    GHR--GPR68    NUMB--GPR68   
Fusion : QuiverGPR68
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGPR68 [hg38]
Exome Variant ServerGPR68
GNOMAD BrowserENSG00000119714
Varsome BrowserGPR68
Genomic Variants (DGV)GPR68 [DGVbeta]
DECIPHERGPR68 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisGPR68 
ICGC Data PortalGPR68 
TCGA Data PortalGPR68 
Broad Tumor PortalGPR68
OASIS PortalGPR68 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGPR68  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DGPR68
Mutations and Diseases : HGMDGPR68
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GPR68
DgiDB (Drug Gene Interaction Database)GPR68
DoCM (Curated mutations)GPR68 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GPR68 (select a term)
NCG6 (London) select GPR68
Cancer3DGPR68(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM601404    617217   
Genetic Testing Registry GPR68
NextProtQ15743 [Medical]
Target ValidationGPR68
Huge Navigator GPR68 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA28911
Clinical trialGPR68
canSAR (ICR)GPR68 (select the gene name)
DataMed IndexGPR68
PubMed39 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Feb 19 17:51:46 CET 2021

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