Trial reportThe Journal of experimental medicine2014
Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding.
Trial report in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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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.
The trial behind it
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Who cites it
67 citing papers in PubMed, 131 citations in OpenAlex.
- Trial
- RAP1-RHO small GTPase cross-talk mediates integrindependent and -independent platelet procoagulant response.Haematologica · 2026Article
- A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.Blood · 2026Article
- [Allogeneic hematopoietic stem cell transplantation for RASGRP2 gene-related inherited platelet function disorders: a case report and literature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Markers for platelet function testing by flow cytometry: where are we now? A clinical perspective.Research and practice in thrombosis and haemostasis · 2026Review
- Multi-omics Mendelian randomization integrating metabolism, microbiome and immunity supports a putative gut-immune-pelvic pathway in deep infiltrating endometriosis.Frontiers in endocrinology · 2026Article
- Implementation and clinical utility of multigene panels for bleeding, platelet, and thrombotic disorders.Journal of thrombosis and haemostasis : JTH · 2025Review
- Roles of G proteins and their GTPase-activating proteins in platelets.Bioscience reports · 2024Review
- Protease-activated receptors and glycoprotein VI cooperatively drive the platelet component in thromboelastography.Journal of thrombosis and haemostasis : JTH · 2023Article
- Article
- The critical role of Rap1-GAPs Rasa3 and Sipa1 in T cells for pulmonary transit and egress from the lymph nodes.Frontiers in immunology · 2023Article
- RASGRP2 is a potential immune-related biomarker and regulates mitochondrial-dependent apoptosis in lung adenocarcinoma.Frontiers in immunology · 2023Article
- Influence of genetic polymorphisms in P2Y12 receptor signaling pathway on antiplatelet response to clopidogrel in coronary heart disease.BMC cardiovascular disorders · 2022Article
- Rasa3 deficiency minimally affects thrombopoiesis but promotes severe thrombocytopenia due to integrin-dependent platelet clearance.JCI insight · 2022Article
- The Connection Between Rap1 and Talin1 in the Activation of Integrins in Blood Cells.Frontiers in cell and developmental biology · 2022Review
- CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant inInternational journal of molecular sciences · 2021Article
- CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors.Neurobiology of disease · 2021Article
- CRISPR-edited megakaryocytes for rapid screening of platelet gene functions.Blood advances · 2021Article
- Observational
- Inherited platelet diseases with normal platelet count: phenotypes, genotypes and diagnostic strategy.Haematologica · 2021Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nature of an inherited platelet disorder was investigated in three siblings affected by severe bleeding. Using whole-exome sequencing, we identified the culprit mutation (cG742T) in the RAS guanyl-releasing protein-2 (RASGRP2) gene coding for calcium- and DAG-regulated guanine exchange factor-1 (CalDAG-GEFI). Platelets from individuals carrying the mutation present a reduced ability to activate Rap1 and to perform proper αIIbβ3 integrin inside-out signaling. Expression of CalDAG-GEFI mutant in HEK293T cells abolished Rap1 activation upon stimulation. Nevertheless, the PKC- and ADP-dependent pathways allow residual platelet activation in the absence of functional CalDAG-GEFI. The mutation impairs the platelet's ability to form thrombi under flow and spread normally as a consequence of reduced Rac1 GTP-binding. Functional deficiencies were confined to platelets and megakaryocytes with no leukocyte alteration. This contrasts with the phenotype seen in type III leukocyte adhesion deficiency caused by the absence of kindlin-3. Heterozygous did not suffer from bleeding and have normal platelet aggregation; however, their platelets mimicked homozygous ones by failing to undergo normal adhesion under flow and spreading. Rescue experiments on cultured patient megakaryocytes corrected the functional deficiency after transfection with wild-type RASGRP2. Remarkably, the presence of a single normal allele is sufficient to prevent bleeding, making CalDAG-GEFI a novel and potentially safe therapeutic target to prevent thrombosis.
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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 OpenQuestion graph.