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P2RY8 (purinergic receptor P2Y, G-protein coupled, 8)

Written2014-11Jill Mackarel, David Betts, Owen Smith
Our Lady's Children's Hospital, Crumlin, Dublin, Ireland

(Note : for Links provided by Atlas : click)


Alias (NCBI)P2Y8
HGNC (Hugo) P2RY8
HGNC Alias symbP2Y8
HGNC Previous namepurinergic receptor P2Y, G-protein coupled, 8
 purinergic receptor P2Y8
LocusID (NCBI) 286530
Atlas_Id 49813
Location Xp22.33  [Link to chromosome band Xp22]
Location_base_pair Starts at 1462581 and ends at 1537185 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping P2RY8.png]
Local_order The P2RY8 gene is located at the pseudoautosomal region 1 (PAR1) of chromosome X and chromosome Y.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CRLF2 (Xp22.33)::P2RY8 (Xp22.33)P2RY8 (Xp22.33)::CRLF2 (Xp22.33)P2RY8 (Xp22.33)::PAX5 (9p13.2)
P2RY8 (Xp22.33)::ZBED1 (Xp22.33)PAX5 (9p13.2)::P2RY8 (Xp22.33)
Note ChrX: 1581465-1656037 base pairs (hg19) from pter (74573 bases).
Orientation: minus strand.
ChrY: 1531465-1606037 (hg19).


  Schematic diagram of the human X chromosome indicating the location of the P2RY8 gene.
Description The P2RY8 gene is located on both chromosomes X and Y. It was discovered by Cantagrel and co-workers while investigating a pericentric inversion on the X chromosome, inv(X)(p22.3 q13.2), in a family with mental retardation. The gene is composed of 4 exons and the promoter region contains the regulatory transcription factor binding sites for , and deltaCREB.
Transcription The transcribed RNA has 4198 base-pairs and encodes a 359 amino acid protein. A second non-encoding transcript exists (splice variant) that has 407 base-pairs.
Pseudogene Fusion gene: a 320-kb large interstitial deletion within the pseudoautosomal region 1 (PAR1) on chromosome X [] and chromosome Y [del(Y)(p11.32p11.32)] results in juxtaposition of the first non-encoding exon of P2RY8 to the CRLF2 coding region to form P2RY8-CRLF2 fusion which leads to over-expression of full-length CRLF2.


Description The protein encoded by P2RY8 gene is composed of 359-amino acids and belongs to the P2Y family of G-protein coupled receptors that are preferentially activated by adenosine and uridine nucleotides. There are eight mammalian P2Y receptors known to date (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13 and P2Y14) and they are found in most human tissues. The specfic function of the P2RY8 receptor remains uncharacterised.
Expression P2RY8 is highly expressed in lymphocytes, with weaker expression in heart, kidney and lung (Cantagrel et al., 2004). Adundant expression of P2RY8 has been demonstrated in bone marrow CD34+ cells in leukaemic patients (Fujiwara et al., 2007). However P2RY8 expression appears to be down-regulated during leucocyte differentiation: normal, mature peripheral blood leucocytes have been shown to have minimal expression, while an undifferentiated promyelocytic leukaemia cell line was shown to have moderate expression of P2RY8 that was down-regulated with induction of granulocyte differentiation (Adrian et al., 2000). Similarly, P2RY8 expression decreases during the differentiation of monocytes to macrophages (Hohenhaus et al., 2013).
Localisation Cell membrane.
Function Using retroviral expression screening for transforming genes in biphenotypic acute leukaemia, P2RY8 has been confirmed to have oncogenic potential (Fujiwara et al., 2007). The P2RY8-CRLF2 fusion is present in 5-7% of paediatric B-cell acute lymphoblastic leukaemia and > 50% of Down syndrome-associated acute lymphoblastic leukaemia (Mullighan et al., 2009; Russell et al., 2009; Cario et al., 2010; Hertzberg et al., 2010; Dyer et al., 2010) and has been identified as a poor prognostic factor associated with high risk disease with an increased risk of relapse (Cario et al., 2010; Ensor et al., 2011; Palmi et al., 2012; Attarbaschi et al., 2012; Yamashita et al., 2013). P2RY8-CRLF2 results in overexpression of full-length cytokine receptor-like factor 2 (CRLF2; also known as the thymic stromal lymphopoietin receptor), which together with IL7 receptor alpha forms a heterodimeric complex that acts at the functional receptor for thymic stromal lymphopoietin (reviewed in Roll and Reuther, 2010). CRLF2 alterations are associated with the presence of activating mutations in the JAK genes JAK1 and JAK2 (Russell et al., 2009; Mullighan et al., 2009; Hertzberg et al., 2010; reviewed in Roll and Reuther, 2010), as well as mutations of the lymphoid transcription factor gene IKZF1 (IKAROS) (Harvey et al., 2010). Although P2RY8-CRLF2 fusions have been confirmed as a clear clinical risk factor in paediatric ALL, their precise role in the leukemic process remains to be elucidated with studies supporting involvement in the cellular transformation process but suggesting they function as a secondary capacity in driving the entire leukemic process (Morak et al., 2012).

Implicated in

Entity B-acute lymphoblastic leukaemia (B-ALL) and Down syndrome-associated acute lymphoblastic leukaemia
Disease As P2RY8-CRLF2 fusion in B-acute lymphoblastic leukaemia (B-ALL) and Down syndrome-associated acute lymphoblastic leukaemia (DS-ALL) (Mullighan et al., 2009; Russell et al., 2009; Cario et al., 2010; Hertzberg et al., 2010; Dyer et al., 2010).
Prognosis Associated with increased relapse risk and overall inferior outcome (Cario et al., 2010; Ensor et al., 2011; Palmi et al., 2012; Attarbaschi et al., 2012; Yamashita et al., 2013).
Cytogenetics Rearrangements are typically G- and R-band cryptic.
Hybrid/Mutated Gene An interstitial deletion of the pseudoautosomal region 1 (PAR1) of either of the sex chromosomes results in juxtaposition of the first noncoding exon of the P2RY8 gene to the first exon of CRLF2, such that CRLF2 expression from this chimeric locus is driven by the P2RY8 promoter.
Oncogenesis Refer to protein function above.
Entity Diffuse large B-cell lymphoma (DLBCL)
Note Coding mutations in P2RY8.
Prognosis Coding mutations were identified in 6 out of 55 patients (11%) with DLBCL using massively parallel whole-exome sequencing. The impact of this mutation on prognosis remains unknown (Lohr et al., 2012).
Oncogenesis The functional consequences of P2RY8 mutation in DLBCL remains to be determined.


Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells.
Adrian K, Bernhard MK, Breitinger HG, Ogilvie A.
Biochim Biophys Acta. 2000 Jun 21;1492(1):127-38.
PMID 11004484
Treatment outcome of CRLF2-rearranged childhood acute lymphoblastic leukaemia: a comparative analysis of the AIEOP-BFM and UK NCRI-CCLG study groups.
Attarbaschi A, Morak M, Cario G, Cazzaniga G, Ensor HM, te Kronnie T, Bradtke J, Mann G, Vendramini E, Palmi C, Schwab C, Russell LJ, Schrappe M, Conter V, Mitchell CD, Strehl S, Zimmermann M, Potschger U, Harrison CJ, Stanulla M, Panzer-Grumayer R, Haas OA, Moorman AV; Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-Berlin-Frankfurt-Munster (BFM) Study Group and National Cancer Research Institute (NCRI)-Children's Cancer and Leukaemia (CCLG) Study Group.
Br J Haematol. 2012 Sep;158(6):772-7. doi: 10.1111/j.1365-2141.2012.09221.x. Epub 2012 Jul 23.
PMID 22816614
Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males.
Cantagrel V, Lossi AM, Boulanger S, Depetris D, Mattei MG, Gecz J, Schwartz CE, Van Maldergem L, Villard L.
J Med Genet. 2004 Oct;41(10):736-42.
PMID 15466006
Presence of the P2RY8-CRLF2 rearrangement is associated with a poor prognosis in non-high-risk precursor B-cell acute lymphoblastic leukemia in children treated according to the ALL-BFM 2000 protocol.
Cario G, Zimmermann M, Romey R, Gesk S, Vater I, Harbott J, Schrauder A, Moericke A, Izraeli S, Akasaka T, Dyer MJ, Siebert R, Schrappe M, Stanulla M.
Blood. 2010 Jul 1;115(26):5393-7. doi: 10.1182/blood-2009-11-256131. Epub 2010 Apr 8.
PMID 20378752
Immunoglobulin heavy chain locus chromosomal translocations in B-cell precursor acute lymphoblastic leukemia: rare clinical curios or potent genetic drivers?
Dyer MJ, Akasaka T, Capasso M, Dusanjh P, Lee YF, Karran EL, Nagel I, Vater I, Cario G, Siebert R.
Blood. 2010 Feb 25;115(8):1490-9. doi: 10.1182/blood-2009-09-235986. Epub 2009 Dec 30. (REVIEW)
PMID 20042721
Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial.
Ensor HM, Schwab C, Russell LJ, Richards SM, Morrison H, Masic D, Jones L, Kinsey SE, Vora AJ, Mitchell CD, Harrison CJ, Moorman AV.
Blood. 2011 Feb 17;117(7):2129-36. doi: 10.1182/blood-2010-07-297135. Epub 2010 Nov 24.
PMID 21106984
Transforming activity of purinergic receptor P2Y, G protein coupled, 8 revealed by retroviral expression screening.
Fujiwara S, Yamashita Y, Choi YL, Watanabe H, Kurashina K, Soda M, Enomoto M, Hatanaka H, Takada S, Ozawa K, Mano H.
Leuk Lymphoma. 2007 May;48(5):978-86.
PMID 17487742
Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia.
Harvey RC, Mullighan CG, Chen IM, Wharton W, Mikhail FM, Carroll AJ, Kang H, Liu W, Dobbin KK, Smith MA, Carroll WL, Devidas M, Bowman WP, Camitta BM, Reaman GH, Hunger SP, Downing JR, Willman CL.
Blood. 2010 Jul 1;115(26):5312-21. doi: 10.1182/blood-2009-09-245944. Epub 2010 Feb 4.
PMID 20139093
Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group.
Hertzberg L, Vendramini E, Ganmore I, Cazzaniga G, Schmitz M, Chalker J, Shiloh R, Iacobucci I, Shochat C, Zeligson S, Cario G, Stanulla M, Strehl S, Russell LJ, Harrison CJ, Bornhauser B, Yoda A, Rechavi G, Bercovich D, Borkhardt A, Kempski H, te Kronnie G, Bourquin JP, Domany E, Izraeli S.
Blood. 2010 Feb 4;115(5):1006-17. doi: 10.1182/blood-2009-08-235408. Epub 2009 Nov 24.
PMID 19965641
An mRNA atlas of G protein-coupled receptor expression during primary human monocyte/macrophage differentiation and lipopolysaccharide-mediated activation identifies targetable candidate regulators of inflammation.
Hohenhaus DM, Schaale K, Le Cao KA, Seow V, Iyer A, Fairlie DP, Sweet MJ.
Immunobiology. 2013 Nov;218(11):1345-53. doi: 10.1016/j.imbio.2013.07.001. Epub 2013 Jul 15.
PMID 23948647
Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing.
Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, Novak AJ, Dogan A, Ansell SM, Link BK, Zou L, Gould J, Saksena G, Stransky N, Rangel-Escareno C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernandez-Lemus E, Schwarz-Cruz y Celis A, Imaz-Rosshandler I, Ojesina AI, Jung J, Pedamallu CS, Lander ES, Habermann TM, Cerhan JR, Shipp MA, Getz G, Golub TR.
Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3879-84. doi: 10.1073/pnas.1121343109. Epub 2012 Feb 17.
PMID 22343534
Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2-harboring clones as main relapse-driving force in childhood ALL.
Morak M, Attarbaschi A, Fischer S, Nassimbeni C, Grausenburger R, Bastelberger S, Krentz S, Cario G, Kasper D, Schmitt K, Russell LJ, Potschger U, Stanulla M, Eckert C, Mann G, Haas OA, Panzer-Grumayer R.
Blood. 2012 Dec 20;120(26):5134-42. doi: 10.1182/blood-2012-07-443218. Epub 2012 Oct 22.
PMID 23091296
Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia.
Mullighan CG, Collins-Underwood JR, Phillips LA, Loudin MG, Liu W, Zhang J, Ma J, Coustan-Smith E, Harvey RC, Willman CL, Mikhail FM, Meyer J, Carroll AJ, Williams RT, Cheng J, Heerema NA, Basso G, Pession A, Pui CH, Raimondi SC, Hunger SP, Downing JR, Carroll WL, Rabin KR.
Nat Genet. 2009 Nov;41(11):1243-6. doi: 10.1038/ng.469. Epub 2009 Oct 18.
PMID 19838194
Poor prognosis for P2RY8-CRLF2 fusion but not for CRLF2 over-expression in children with intermediate risk B-cell precursor acute lymphoblastic leukemia.
Palmi C, Vendramini E, Silvestri D, Longinotti G, Frison D, Cario G, Shochat C, Stanulla M, Rossi V, Di Meglio AM, Villa T, Giarin E, Fazio G, Leszl A, Schrappe M, Basso G, Biondi A, Izraeli S, Conter V, Valsecchi MG, Cazzaniga G, Te Kronnie G.
Leukemia. 2012 Oct;26(10):2245-53. doi: 10.1038/leu.2012.101. Epub 2012 Apr 9.
PMID 22484421
CRLF2 and JAK2 in B-progenitor acute lymphoblastic leukemia: a novel association in oncogenesis.
Roll JD, Reuther GW.
Cancer Res. 2010 Oct 1;70(19):7347-52. doi: 10.1158/0008-5472.CAN-10-1528. Epub 2010 Aug 31. (REVIEW)
PMID 20807819
Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia.
Russell LJ, Capasso M, Vater I, Akasaka T, Bernard OA, Calasanz MJ, Chandrasekaran T, Chapiro E, Gesk S, Griffiths M, Guttery DS, Haferlach C, Harder L, Heidenreich O, Irving J, Kearney L, Nguyen-Khac F, Machado L, Minto L, Majid A, Moorman AV, Morrison H, Rand V, Strefford JC, Schwab C, Tonnies H, Dyer MJ, Siebert R, Harrison CJ.
Blood. 2009 Sep 24;114(13):2688-98. doi: 10.1182/blood-2009-03-208397. Epub 2009 Jul 29.
PMID 19641190
IKZF1 and CRLF2 gene alterations correlate with poor prognosis in Japanese BCR-ABL1-negative high-risk B-cell precursor acute lymphoblastic leukemia.
Yamashita Y, Shimada A, Yamada T, Yamaji K, Hori T, Tsurusawa M, Watanabe A, Kikuta A, Asami K, Saito AM, Horibe K.
Pediatr Blood Cancer. 2013 Oct;60(10):1587-92. doi: 10.1002/pbc.24571. Epub 2013 Jun 27.
PMID 23804397


This paper should be referenced as such :
Jill Mackarel, David Betts, Owen Smith
P2RY8 (purinergic receptor P2Y, G-protein coupled, 8)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(12):705-707.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 7 ]
  del(X)(p22p22) P2RY8::CRLF2::del(Y)(p11p11) P2RY8::CRLF2
Acute lymphoblastic leukemia in Down syndrome
+X solely in ALL
t(X;14)(p22;q32) or t(Y;14)(p11;q32) IGH::CRLF2
P2RY8::ZBED1 (Xp22)
t(X;9)(p22;p13) P2RY8::PAX5
t(X;9)(p22;p13) PAX5::P2RY8

External links


HGNC (Hugo)P2RY8   15524
Atlas Explorer : (Salamanque)P2RY8
Entrez_Gene (NCBI)P2RY8    P2Y receptor family member 8
GeneCards (Weizmann)P2RY8
Ensembl hg19 (Hinxton)ENSG00000182162 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000182162 [Gene_View]  ENSG00000182162 [Sequence]  chrX:1462581-1537185 [Contig_View]  P2RY8 [Vega]
ICGC DataPortalENSG00000182162
TCGA cBioPortalP2RY8
AceView (NCBI)P2RY8
Genatlas (Paris)P2RY8
SOURCE (Princeton)P2RY8
Genetics Home Reference (NIH)P2RY8
Genomic and cartography
GoldenPath hg38 (UCSC)P2RY8  -     chrX:1462581-1537185 -  X;Y   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)P2RY8  -     X;Y   [Description]    (hg19-Feb_2009)
GoldenPathP2RY8 - X;Y [CytoView hg19]  P2RY8 - X;Y [CytoView hg38]
Genome Data Viewer NCBIP2RY8 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AI476104 AI494365 AK092956 AL833184 BC012792
RefSeq transcript (Entrez)NM_178129
Consensus coding sequences : CCDS (NCBI)P2RY8
Gene ExpressionP2RY8 [ NCBI-GEO ]   P2RY8 [ EBI - ARRAY_EXPRESS ]   P2RY8 [ SEEK ]   P2RY8 [ MEM ]
Gene Expression Viewer (FireBrowse)P2RY8 [ Firebrowse - Broad ]
GenevisibleExpression of P2RY8 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)286530
GTEX Portal (Tissue expression)P2RY8
Human Protein AtlasENSG00000182162-P2RY8 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ86VZ1   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ86VZ1  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ86VZ1
Domaine pattern : Prosite (Expaxy)G_PROTEIN_RECEP_F1_1 (PS00237)    G_PROTEIN_RECEP_F1_2 (PS50262)   
Domains : Interpro (EBI)GPCR_Rhodpsn    GPCR_Rhodpsn_7TM    P2Y8_rcpt   
Domain families : Pfam (Sanger)7tm_1 (PF00001)   
Domain families : Pfam (NCBI)pfam00001   
Conserved Domain (NCBI)P2RY8
AlphaFold pdb e-kbQ86VZ1   
Human Protein Atlas [tissue]ENSG00000182162-P2RY8 [tissue]
Protein Interaction databases
IntAct (EBI)Q86VZ1
Ontologies - Pathways
Ontology : AmiGOG protein-coupled receptor activity  integral component of plasma membrane  positive regulation of Rho protein signal transduction  G protein-coupled purinergic nucleotide receptor signaling pathway  G protein-coupled purinergic nucleotide receptor activity  positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway  
Ontology : EGO-EBIG protein-coupled receptor activity  integral component of plasma membrane  positive regulation of Rho protein signal transduction  G protein-coupled purinergic nucleotide receptor signaling pathway  G protein-coupled purinergic nucleotide receptor activity  positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway  
NDEx NetworkP2RY8
Atlas of Cancer Signalling NetworkP2RY8
Wikipedia pathwaysP2RY8
Orthology - Evolution
GeneTree (enSembl)ENSG00000182162
Phylogenetic Trees/Animal Genes : TreeFamP2RY8
Homologs : HomoloGeneP2RY8
Homology/Alignments : Family Browser (UCSC)P2RY8
Gene fusions - Rearrangements
Fusion : MitelmanP2RY8::CRLF2 [Xp22.33/Xp22.33]  
Fusion : QuiverP2RY8
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerP2RY8 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)P2RY8
Exome Variant ServerP2RY8
GNOMAD BrowserENSG00000182162
Varsome BrowserP2RY8
ACMGP2RY8 variants
Genomic Variants (DGV)P2RY8 [DGVbeta]
DECIPHERP2RY8 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisP2RY8 
ICGC Data PortalP2RY8 
TCGA Data PortalP2RY8 
Broad Tumor PortalP2RY8
OASIS PortalP2RY8 [ Somatic mutations - Copy number]
Cancer Gene: CensusP2RY8 
Somatic Mutations in Cancer : COSMICP2RY8  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DP2RY8
Mutations and Diseases : HGMDP2RY8
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)P2RY8
DoCM (Curated mutations)P2RY8
CIViC (Clinical Interpretations of Variants in Cancer)P2RY8
NCG (London)P2RY8
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry P2RY8
NextProtQ86VZ1 [Medical]
Target ValidationP2RY8
Huge Navigator P2RY8 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDP2RY8
Pharm GKB GenePA32873
Clinical trialP2RY8
DataMed IndexP2RY8
PubMed21 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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