P2RY8

P2RY8 encodes a G protein–coupled receptor that is expressed on germinal center B cells. Signals through this receptor promote confinement of B cells to the GC niche.¹ Downstream signaling through Galpha13 (encoded by GNA13) and S1PR2 is distrupted by mutations of one of these genes in GC lymphomas including the GCB subgroup of DLBCL² and BL.¹

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence BL gene
	1	high-confidence DLBCL gene
	2	relevance in FL not firmly established

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	6.93
BL	Thomas cohort	11.00
BL	Panea cohort	NA
DLBCL	GAMBL genomes	6.88
DLBCL	Schmitz cohort	7.23
DLBCL	Reddy cohort	NA
DLBCL	Chapuy cohort	5.98
FL	GAMBL genomes	2.31

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	Yes	58.153	189.145
DLBCL	No	Yes	31.041	0.000
FL	No	No	23.117	0.000

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

P2RY8 Expression

References

1. Muppidi JR, Schmitz R, Green JA, Xiao W, Larsen AB, Braun SE, An J, Xu Y, Rosenwald A, Ott G, Gascoyne RD, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Vaidehi N, Staudt LM, Cyster JG. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature. 2014 Dec 11;516(7530):254-8. doi: 10.1038/nature13765. Epub 2014 Sep 28. PMID: 25274307; PMCID: PMC4267955.
2. 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-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernández-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. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. 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; PMCID: PMC3309757.