| HGNC Family | G protein-coupled receptors |
| Name | G protein-coupled receptor 21 |
| Description | This gene encodes a member of the G-protein-coupled receptor 1 family. G-protein coupled receptors are membrane proteins which activate signaling cascades as a response to extracellular stress. The encoded protein activates a Gq signal transduction pathway which mobilizes calcium. [provided by RefSeq, Nov 2012] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGPR21 is an orphan G protein-coupled receptor that exhibits high constitutive activity and plays a multifaceted role in metabolic regulation. Studies in metabolic tissues have demonstrated that overexpression of GPR21 in high fat high sugar models correlates with obesity-associated insulin resistance by engaging Gαq proteins to activate mitogen-activated protein kinases (MAPKs), thereby attenuating insulin signaling. Structural investigations have further unraveled unique receptor features, including an agonist-like motif in extracellular loop 2 that occupies the orthosteric pocket and a side pocket that may serve as an innovative ligand binding site. These insights suggest that targeting GPR21 could offer a novel pharmacological strategy for type 2 diabetes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nDiscrepancies in animal model studies have hinted at a broader role for GPR21 in modulating immune functions, particularly in linking tissue immune cell infiltration to obesity-induced insulin resistance. Further investigations in human macrophages reveal that GPR21 not only contributes to cell migration but also influences cytokine release, where its pharmacological inhibition with an inverse agonist markedly reduces pro-inflammatory mediators such as TNF-α and IL-1β. These findings underscore GPR21’s potential as a therapeutic target for conditions characterized by chronic low-grade inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Siobhán Leonard, Gemma K Kinsella, Elisa Benetti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulating the effects of GPR21, a novel target for type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep27002"}], "href": "https://doi.org/10.1038/srep27002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27243589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27243589"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xi Lin, Bo Chen, Yiran Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cryo-EM structures of orphan GPR21 signaling complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-023-35882-w"}], "href": "https://doi.org/10.1038/s41467-023-35882-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36639690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36639690"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Darren M Riddy, Helene L Kammoun, Andrew J Murphy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of GPR21 improves glucose homeostasis and inhibits the CCL2-CCR2 axis by divergent mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMJ Open Diabetes Res Care (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/bmjdrc-2021-002285"}], "href": "https://doi.org/10.1136/bmjdrc-2021-002285"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34782333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34782333"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Valentina Bordano, Gemma K Kinsella, Stefania Cannito, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G protein-coupled receptor 21 in macrophages: An in vitro study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2022.175018"}], "href": "https://doi.org/10.1016/j.ejphar.2022.175018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35537492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35537492"}]}]}]}
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| Proteins | GPR21_HUMAN |
| NCBI Gene ID | 2844 |
| 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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GPR21 has 2,950 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 73 datasets.
Click the + buttons to view associations for GPR21 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 GPR21 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 GPR21 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 GPR21 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 GPR21 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq | tissue samples with high or low expression of GPR21 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of GPR21 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of GPR21 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of GPR21 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of GPR21 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of GPR21 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of GPR21 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 GPR21 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 GPR21 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of GPR21 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 GPR21 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 GPR21 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of GPR21 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing GPR21 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with GPR21 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 GPR21 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with GPR21 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Disease Associations | diseases associated with GPR21 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by GPR21 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with GPR21 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with GPR21 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 GPR21 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at GPR21 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 GPR21 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of GPR21 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing GPR21 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of GPR21 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing GPR21 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of GPR21 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 GPR21 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 GPR21 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 GPR21 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 GPR21 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving GPR21 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing GPR21 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by GPR21 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by GPR21 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with GPR21 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of GPR21 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of GPR21 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of GPR21 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for GPR21 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of GPR21 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of GPR21 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of GPR21 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 GPR21 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 GPR21 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain GPR21 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by GPR21 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of GPR21 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MPO Gene-Phenotype Associations | phenotypes of transgenic mice caused by GPR21 gene mutations from the MPO Gene-Phenotype Associations dataset. | |
| NURSA Protein Complexes | protein complexs containing GPR21 protein recovered by IP-MS from the NURSA Protein Complexes dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for GPR21 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of GPR21 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving GPR21 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving GPR21 protein from the Wikipathways PFOCR 2024 dataset. | |
| Roadmap Epigenomics Cell and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of GPR21 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at GPR21 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of GPR21 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of GPR21 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of GPR21 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of GPR21 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of GPR21 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of GPR21 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of GPR21 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with GPR21 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 GPR21 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2014 | pathways involving GPR21 protein from the Wikipathways Pathways 2014 dataset. | |
| WikiPathways Pathways 2024 | pathways involving GPR21 protein from the WikiPathways Pathways 2024 dataset. | |
