| HGNC Family | G protein-coupled receptors |
| Name | MAS-related GPR, member X4 |
| Description | Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within chemosensory behavior and hematopoietic progenitor cell differentiation. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMRGPRX4 is a member of the mas‐related G protein–coupled receptor family that has been characterized by recent structural studies revealing its activation mechanisms. Notably, high‐resolution structures have captured agonist‐bound complexes that detail its coupling primarily to Gq proteins – insights that are crucial for the rational design of therapeutics targeting pain, itch, and mast cell–mediated hypersensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, unbiased high‐throughput screens coupled with cryo–electron microscopy have demonstrated that phosphate‐modified drugs, commonly employed to improve solubility, potently activate MRGPRX4; these findings explain the often treatment–limiting pruritus associated with such compounds."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n \n \nMRGPRX4 also functions as a critical receptor for bile acids and bilirubin in human sensory neurons, where its activation has been directly linked to the severe, chronic itch seen in cholestatic liver disease. Studies employing Ca2⁺ imaging in vitro and humanized mouse models have shown that pathophysiologically relevant bile acid concentrations robustly stimulate MRGPRX4, thereby eliciting itch."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, genetic analyses have identified naturally occurring variants in MRGPRX4—particularly a haplotype present among individuals of African ancestry—that reduce receptor agonism and are associated with an increased propensity for mentholated cigarette smoking."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Further complexity in receptor regulation is provided by its interaction with receptor activity–modifying protein 2 (RAMP2), which attenuates both basal and agonist–dependent signaling by reducing MRGPRX4 cell surface expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Recent reviews have consolidated these observations, firmly establishing MRGPRX4 as a bile acid and bilirubin receptor central to the development of cholestatic itch and thereby identifying it as a promising therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Can Cao, Hye Jin Kang, Isha Singh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure, function and pharmacology of human itch GPCRs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-021-04126-6"}], "href": "https://doi.org/10.1038/s41586-021-04126-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34789874"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34789874"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daphne Chun-Che Chien, Nathachit Limjunyawong, Can Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MRGPRX4 mediates phospho-drug-associated pruritus in a humanized mouse model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Transl Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scitranslmed.adk8198"}], "href": "https://doi.org/10.1126/scitranslmed.adk8198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38718132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38718132"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "James Meixiong, Chirag Vasavda, Solomon H Snyder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MRGPRX4 is a G protein-coupled receptor activated by bile acids that may contribute to cholestatic pruritus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1903316116"}], "href": "https://doi.org/10.1073/pnas.1903316116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31068464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31068464"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Huasheng Yu, Tianjun Zhao, Simin Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MRGPRX4 is a bile acid receptor for human cholestatic itch."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.48431"}], "href": "https://doi.org/10.7554/eLife.48431"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31500698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31500698"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Julia Kozlitina, Davide Risso, Katherine Lansu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An African-specific haplotype in MRGPRX4 is associated with menthol cigarette smoking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1007916"}], "href": "https://doi.org/10.1371/journal.pgen.1007916"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30768591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30768591"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ilana B Kotliar, Emilie Ceraudo, Kevin Kemelmakher-Liben, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Itch receptor MRGPRX4 interacts with the receptor activity-modifying proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2023.104664"}], "href": "https://doi.org/10.1016/j.jbc.2023.104664"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37003505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37003505"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Huasheng Yu, Kirk Wangensteen, Tong Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MRGPRX4 in Cholestatic Pruritus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Semin Liver Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-0041-1730923"}], "href": "https://doi.org/10.1055/s-0041-1730923"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34161994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34161994"}]}]}]}
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| Synonyms | MRGX4, SNSR6 |
| Proteins | MRGX4_HUMAN |
| NCBI Gene ID | 117196 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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MRGPRX4 has 1,633 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 62 datasets.
Click the + buttons to view associations for MRGPRX4 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of MRGPRX4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles | tissues with high or low expression of MRGPRX4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of MRGPRX4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of MRGPRX4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of MRGPRX4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of MRGPRX4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of MRGPRX4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of MRGPRX4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of MRGPRX4 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of MRGPRX4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of MRGPRX4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of MRGPRX4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing MRGPRX4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with MRGPRX4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of MRGPRX4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with MRGPRX4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by MRGPRX4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores | diseases associated with MRGPRX4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with MRGPRX4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with MRGPRX4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with MRGPRX4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with MRGPRX4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at MRGPRX4 gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of MRGPRX4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of MRGPRX4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GAD Gene-Disease Associations | diseases associated with MRGPRX4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing MRGPRX4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of MRGPRX4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of MRGPRX4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of MRGPRX4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of MRGPRX4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of MRGPRX4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of MRGPRX4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving MRGPRX4 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing MRGPRX4 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by MRGPRX4 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by MRGPRX4 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by MRGPRX4 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of MRGPRX4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of MRGPRX4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of MRGPRX4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with MRGPRX4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by MRGPRX4 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for MRGPRX4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of MRGPRX4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of MRGPRX4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of MRGPRX4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of MRGPRX4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain MRGPRX4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by MRGPRX4 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of MRGPRX4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| NURSA Protein Complexes | protein complexs containing MRGPRX4 protein recovered by IP-MS from the NURSA Protein Complexes dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of MRGPRX4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at MRGPRX4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of MRGPRX4 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of MRGPRX4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of MRGPRX4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of MRGPRX4 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of MRGPRX4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with MRGPRX4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with MRGPRX4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2014 | pathways involving MRGPRX4 protein from the Wikipathways Pathways 2014 dataset. | |
