Evidence map›Paper›PMID 40930105›Full record

ArticleCell genomics2025

Phenotypic pleiotropy of missense variants in human B cell confinement receptor P2RY8.

Taylor N LaFlam, Christian B Billesbølle, Tuan Dinh, Finn D Wolfreys, Erick Lu, Tomas Matteson, Jinping An, Ying Xu, Arushi Singhal, Nadav Brandes and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Taylor N LaFlamDivision of Pediatric Rheumatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA. Electronic address: taylor.laflam@ucsf.edu.
Christian B BillesbølleDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Tuan DinhDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Finn D WolfreysDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
Erick LuDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
Tomas MattesonDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Jinping AnDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
Ying XuDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
Arushi SinghalGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Nadav BrandesDepartment of Biochemistry and Molecular Pharmacology, New York University, New York, NY, USA.
Vasilis NtranosDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
Aashish ManglikDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA; Quantitative Biosciences Institute, San Francisco, CA, USA; Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
Jason G CysterDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA. Electronic address: jason.cyster@ucsf.edu.
Chun Jimmie YeGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA, USA; Arc Institute, Palo Alto, CA, USA. Electronic address: jimmie.ye@ucsf.edu.

Funding

RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
NIAMS NIH HHS P30 AR070155
6 · The paper itself

Abstract

Missense variants can have pleiotropic effects on protein function, and predicting these effects can be difficult. We performed near-saturation deep mutational scanning of P2RY8, a G protein-coupled receptor that promotes germinal center B cell confinement. We assayed the effect of each variant on surface expression, migration, and proliferation. We delineated variants that affected both expression and function, affected function independently of expression, and discrepantly affected migration and proliferation. We also used cryo-electron microscopy to determine the structure of activated, ligand-bound P2RY8, providing structural insights into the effects of variants on ligand binding and signal transmission. We applied the deep mutational scanning results to both improve computational variant effect predictions and to characterize the phenotype of germline variants and lymphoma-associated variants. Together, our results demonstrate the power of integrating deep mutational scanning, structure determination, and in silico prediction to advance the understanding of a receptor important in human health.

Indexed as

B-LymphocytesGenetic PleiotropyMutation, MissenseCell MovementCell ProliferationCryoelectron MicroscopyHumansPhenotypeB cellscryo-EMdeep mutational scanningfunctional genomicsGPCRlymphomamultiplexed assays of variant effectP2RY8variant effect prediction

Identifiers

PMID40930105
PMCPMC12648108

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.