Last update 01 Nov 2024

MRGPRX1

Last update 01 Nov 2024

Basic Info

Synonyms

MAS related GPR family member X1, Mas-related G-protein coupled receptor member X1, MAS-related GPR, member X1

+ [5]

Introduction

Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain. Potently activated by enkephalins including BAM22 (bovine adrenal medulla peptide 22) and BAM (8-22)(PubMed:26582731). BAM22 is the most potent compound and evoked a large and dose-dependent release of intracellular calcium in stably transfected cells. G(alpha)q proteins are involved in the calcium-signaling pathway. Activated by the antimalarial drug, chloroquine. May mediate chloroquine-induced itch, in a histamine-independent manner.

Drugs associated with MRGPRX1

ML382

Target

MRGPRX1

Mechanism

MRGPRX1 agonists

Active Org.

Vanderbilt University

Originator Org.

Vanderbilt University

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MRGPRX1 antagonists(Escient Pharmaceuticals)

Target

MRGPRX1

Mechanism

MRGPRX1 antagonists

Active Org.

Escient Pharmaceuticals, Inc.Startup

Originator Org.

Escient Pharmaceuticals, Inc.Startup

Active Indication-

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MRGPRX1

100 Translational Medicine associated with MRGPRX1

0 Patents (Medical) associated with MRGPRX1

Literatures (Medical) associated with MRGPRX1

01 Nov 2024·Pain

RNA isoform expression landscape of the human dorsal root ganglion generated from long-read sequencing

Article

Author: Mwirigi, Juliet M ; Price, Theodore J ; Arendt-Tranholm, Asta

AbstractSplicing is a posttranscriptional RNA processing mechanism that enhances genomic complexity by creating multiple isoforms from the same gene. We aimed to characterize the isoforms expressed in the human peripheral nervous system, with the goal of creating a resource to identify novel isoforms of functionally relevant genes associated with somatosensation and nociception. We used long-read sequencing to document isoform expression in the human dorsal root ganglia from 3 organ donors and validated in silico by confirming expression in short-read sequencing from 3 independent organ donors. Nineteen thousand five hundred forty-seven isoforms of protein-coding genes were detected and validated. We identified 763 isoforms with at least one previously undescribed splice junction. Previously unannotated isoforms of multiple pain-associated genes, including ASIC3, MRGPRX1, and HNRNPK, were identified. In the novel isoforms of ASIC3, a region comprising approximately 35% of the 5'UTR was excised. By contrast, a novel splice junction was used in isoforms of MRGPRX1 to include an additional exon upstream of the start codon, consequently adding a region to the 5'UTR. Novel isoforms of HNRNPK were identified, which used previously unannotated splice sites to both excise exon 14 and include a sequence in the 3' end of exon 13. This novel insertion is predicted to introduce a tyrosine phosphorylation site potentially phosphorylated by SRC. We also independently confirm a recently reported DRG-specific splicing event in WNK1 that gives insight into how painless peripheral neuropathy occurs when this gene is mutated. Our findings give a clear overview of mRNA isoform diversity in the human dorsal root ganglia obtained using long-read sequencing.

01 Aug 2024·Environment International

Common genetic variants associated with urinary phthalate levels in children: A genome-wide study

Article

Author: Ruiz-Arenas, Carlos ; Wright, John ; Gützkow, Kristine B ; Casas, Maribel ; Andrusaityte, Sandra ; Brantsæter, Anne-Lise ; Philippat, Claire ; Sakhi, Amrit Kaur ; Escaramís, Geòrgia ; Thomsen, Cathrine ; Maitre, Lea ; Chatzi, Leda ; Heude, Barbara ; Hough, Amy ; Yang, Tiffany C ; Buko, Zsanett ; Nurtdinov, Ramil N ; González, Juan R ; Grazuleviciene, Regina ; Bustamante, Mariona ; Vrijheid, Martine ; Vafeiadi, Marina ; Balagué-Dobón, Laura

INTRODUCTIONPhthalates, or dieters of phthalic acid, are a ubiquitous type of plasticizer used in a variety of common consumer and industrial products. They act as endocrine disruptors and are associated with increased risk for several diseases. Once in the body, phthalates are metabolized through partially known mechanisms, involving phase I and phase II enzymes.OBJECTIVEIn this study we aimed to identify common single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) associated with the metabolism of phthalate compounds in children through genome-wide association studies (GWAS).METHODSThe study used data from 1,044 children with European ancestry from the Human Early Life Exposome (HELIX) cohort. Ten phthalate metabolites were assessed in a two-void pooled urine collected at the mean age of 8 years. Six ratios between secondary and primary phthalate metabolites were calculated. Genome-wide genotyping was done with the Infinium Global Screening Array (GSA) and imputation with the Haplotype Reference Consortium (HRC) panel. PennCNV was used to estimate copy number variants (CNVs) and CNVRanger to identify consensus regions. GWAS of SNPs and CNVs were conducted using PLINK and SNPassoc, respectively. Subsequently, functional annotation of suggestive SNPs (p-value < 1E-05) was done with the FUMA web-tool.RESULTSWe identified four genome-wide significant (p-value < 5E-08) loci at chromosome (chr) 3 (FECHP1 for oxo-MiNP_oh-MiNP ratio), chr6 (SLC17A1 for MECPP_MEHHP ratio), chr9 (RAPGEF1 for MBzP), and chr10 (CYP2C9 for MECPP_MEHHP ratio). Moreover, 115 additional loci were found at suggestive significance (p-value < 1E-05). Two CNVs located at chr11 (MRGPRX1 for oh-MiNP and SLC35F2 for MEP) were also identified. Functional annotation pointed to genes involved in phase I and phase II detoxification, molecular transfer across membranes, and renal excretion.CONCLUSIONThrough genome-wide screenings we identified known and novel loci implicated in phthalate metabolism in children. Genes annotated to these loci participate in detoxification, transmembrane transfer, and renal excretion.

01 Jun 2024·Journal of Investigative Dermatology

The Fungal Secretory Peptide Micasin Induces Itch by Activating MRGPRX1/C11/A1 on Peripheral Neurons

Article

Author: Yu, Leiye ; Gan, Bing ; Kwok, Hang Fai ; Wu, Yingliang ; Cao, Zhijian ; Yang, Haifeng ; Ren, Ruobing ; Chen, Yian ; Wang, Luyao

Pruritus is the leading symptom of dermatophytosis. Microsporium canis is one of the predominant dermatophytes causing dermatophytosis. However, the pruritogenic agents and the related molecular mechanisms of the dermatophyte M canis remain poorly understood. In this study, the secretion of the dermatophyte M canis was found to dose-dependently evoke itch in mice. The fungal peptide micasin secreted from M canis was then identified to elicit mouse significant scratching and itching responses. The peptide micasin was further revealed to directly activate mouse dorsal root ganglia neurons to mediate the nonhistaminergic itch. Knockout and antagonistic experiments demonstrated that MRGPRX1/C11/A1 rather than MRGPRX2/b2 activated by micasin contributed to pruritus. The chimeras and single-amino acid variants of MRGPRX1 showed that 3 domains (extracellular loop 3, transmembrane helical domain 3, and transmembrane helical domain 6) and 4 hydrophobic residues (Y99, F237, L240, and W241) of MRGPRX1 played the key role in micasin-triggered MRGPRX1 activation. Our study sheds light on the dermatophytosis-associated pruritus and may provide potential therapeutic targets and strategies against pruritus caused by dermatophytes.

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MRGPRX1

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