ArticleJournal of immunology (Baltimore, Md. : 1950)2018
Naturally Occurring Missense MRGPRX2 Variants Display Loss of Function Phenotype for Mast Cell Degranulation in Response to Substance P, Hemokinin-1, Human β-Defensin-3, and Icatibant.
Article in Journal of immunology (Baltimore, Md. : 1950), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Neurotransmitter and neuropeptide regulation of mast cell function: a systematic review.Journal of neuroinflammation · 2020Pooled it
- Article
- In silico discovery of nanobody binders to a G-protein coupled receptor using AlphaFold-Multimer.Nature communications · 2026Article
- Direct protamine activation of human mast cells is MRGPRX2-dependent and is modulated by heparin.The Journal of pharmacology and experimental therapeutics · 2026Article
- LL-37-MRGPRX2-Mast Cell Signaling in Rosacea: Current Evidence and Directions for Human Studies.Clinical, cosmetic and investigational dermatology · 2026Review
- Modulation of Mast Cell Activation via MRGPRX2 by Natural Oat Extract.International journal of molecular sciences · 2025Article
- Evaluation of the Effects of Chitin and Chitosan on Pseudo-Allergic Reaction by Inhibiting MRGPRX2 Activation.Food science & nutrition · 2025Article
- Icatibant Acts as a Balanced Ligand of MRGPRX2 in Human Skin Mast Cells.Biomolecules · 2025Article
- Mutations ofThe journal of allergy and clinical immunology. Global · 2025Review
- Beyond the classic players: Mas-related G protein-coupled receptor member X2 role in pruritus and skin diseases.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Review
- Advances in MRGPRX2-mediated anaphylactoid reactions to traditional Chinese medicine injections.Frontiers in pharmacology · 2025Review
- Amphotericin B for injection triggers degranulation of human LAD2 mast cells by MRGPRX2 and pseudo-allergic reactions in mice via MRGPRB2 activation.Immunologic research · 2024Article
- A Skin Testing Strategy for Non-IgE-Mediated Reactions Associated With Vancomycin.The journal of allergy and clinical immunology. In practice · 2024Article
- Article
- Non-IgE-Mediated Immediate Drug-Induced Hypersensitivity Reactions.The journal of allergy and clinical immunology. In practice · 2024Article
- Functional MRGPRX2 expression on peripheral blood-derived human mast cells increases at low seeding density and is suppressed by interleukin-9 and fetal bovine serum.Frontiers in immunology · 2024Article
- The development of murine bone marrow-derived mast cells expressing functional human MRGPRX2 forFrontiers in immunology · 2024Article
- Recent insights into the mechanisms of anaphylaxis.Current opinion in immunology · 2023Review
- The structure, function, and pharmacology of MRGPRs.Trends in pharmacological sciences · 2023Review
- Patient Characteristics Associated With Reactions to Mrgprx2-Activating Drugs in an Electronic Health Record-Linked Biobank.The journal of allergy and clinical immunology. In practice · 2023Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human mast cells (MCs) express a novel G protein-coupled receptor (GPCR) known as Mas-related GPCR X2 (MRGPRX2). Activation of this receptor by a diverse group of cationic ligands such as neuropeptides, host defense peptides, and Food and Drug Administration-approved drugs contributes to chronic inflammatory diseases and pseudoallergic drug reactions. For most GPCRs, the extracellular (ECL) domains and their associated transmembrane (TM) domains display the greatest structural diversity and are responsible for binding different ligands. The goal of the current study was to determine if naturally occurring missense variants within MRGPRX2's ECL/TM domains contribute to gain or loss of function phenotype for MC degranulation in response to neuropeptides (substance P and hemokinin-1), a host defense peptide (human β-defensin-3) and a Food and Drug Administration-approved cationic drug (bradykinin B2 receptor antagonist, icatibant). We have identified eight missense variants within MRGPRX2's ECL/TM domains from publicly available exome-sequencing databases. We investigated the ability of MRGPRX2 ligands to induce degranulation in rat basophilic leukemia-2H3 cells individually expressing these naturally occurring MRGPRX2 missense variants. Using stable and transient transfections, we found that all variants express in rat basophilic leukemia cells. However, four natural MRGPRX2 variants, G165E (rs141744602), D184H (rs372988289), W243R (rs150365137), and H259Y (rs140862085) failed to respond to any of the ligands tested. Thus, diverse MRGPRX2 ligands use common sites on the receptor to induce MC degranulation. These findings have important clinical implications for MRGPRX2 and MC-mediated pseudoallergy and chronic inflammatory diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.