HGNC Family | G protein-coupled receptors |
Name | relaxin/insulin-like family peptide receptor 2 |
Description | This gene encodes a member of the GPCR (G protein-coupled, 7-transmembrane receptor) family. Mutations in this gene are associated with cryptorchidism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009] |
Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRXFP2 is a G protein–coupled receptor that serves as the cognate binding partner for insulin‐like peptide 3 (INSL3) and, under certain conditions, relaxin. A large body of work establishes its essential function in male reproductive development, particularly during testicular descent, where genetic mutations or splice‐variant alterations (including the recurrent T222P mutation) can lead to cryptorchidism and related gonadal dysgenesis. Moreover, disruption of RXFP2 signaling has been linked not only to maldescent of the testes but also to anomalies in germ cell function and male fertility. Collectively, these studies support a critical developmental role for RXFP2 in the reproductive system and underscore its relevance in clinical conditions such as anorchia and cryptorchidism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, RXFP2 exhibits a complex architecture characterized by an extensive extracellular domain with leucine‐rich repeats and a unique N‐terminal low–density lipoprotein class A (LDLa) module that is indispensable for signal transduction. Detailed structure–function analyses have demonstrated that while the primary hormone binding relies on B‐chain residues of INSL3 (and in some cases relaxin), efficient receptor activation, cAMP signaling, and downstream responses depend on the integrity of the LDLa module and proper receptor processing. Investigations using splice variants, point mutations, and receptor chimeras have further clarified that minor changes in the extracellular domain can completely abrogate signaling despite preserved ligand binding, thereby highlighting the intricate molecular mechanisms underlying RXFP2 activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role in reproductive development, emerging evidence demonstrates that RXFP2 signaling has broader physiological and pathophysiological implications. In adults, RXFP2 activation influences bone metabolism, as mutations have been associated with reduced bone density, and it is expressed in osteoblasts where it modulates cell proliferation and differentiation. RXFP2 is also found in other tissues such as the ocular surface and spermatozoa, where it contributes to corneal wound healing and confers anti‐apoptotic as well as antioxidant effects that may enhance sperm motility and genomic integrity. Furthermore, recent genetic and pharmacological studies have implicated RXFP2 in cardiovascular regulation—in particular, in the context of resistant hypertension—thus proposing RXFP2 antagonism as a novel therapeutic avenue. Though its role in other conditions such as varicosis remains to be fully elucidated, the multifaceted actions of RXFP2 continue to emerge, highlighting its potential as a drug target in reproductive, skeletal, and cardiovascular disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "26", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alberto Ferlin, Mauro Simonato, Lucia Bartoloni, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Human amniotic fluid-based exposure levels of phthalates and bisphenol A mixture reduce INSL3/RXFP2 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Int (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.envint.2020.105585"}], "href": "https://doi.org/10.1016/j.envint.2020.105585"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32126385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32126385"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Saeed Shokri, Marziyeh Tavalaee, Seyyed Meisam Ebrahimi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of RXFP2 receptor on human spermatozoa and the anti-apoptotic and antioxidant effects of insulin-like factor 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Andrologia (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/and.13715"}], "href": "https://doi.org/10.1111/and.13715"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32557760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32557760"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Ann-Kristin Dicke, Jakob Albrethsen, Bradley L Hoare, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic variants in INSL3 and RXFP2 cause bilateral cryptorchidism and male infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dead105"}], "href": "https://doi.org/10.1093/humrep/dead105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37208861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37208861"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Shan-Shan Zhang, Lance Larrabee, Andrew H Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discovery of RXFP2 genetic association in resistant hypertensive men and RXFP2 antagonists for the treatment of resistant hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-024-62804-7"}], "href": "https://doi.org/10.1038/s41598-024-62804-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38851835"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38851835"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Hannes Syryn, Julie Van de Velde, Griet De Clercq, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic RXFP2 variants lead to congenital bilateral cryptorchidism and male infertility, supporting a role of RXFP2 in spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/deae195"}], "href": "https://doi.org/10.1093/humrep/deae195"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39222519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39222519"}]}]}]}
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Synonyms | GPR106, INSL3R, LGR8.1, RXFPR2, LGR8, GREAT |
Proteins | RXFP2_HUMAN |
NCBI Gene ID | 122042 |
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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RXFP2 has 2,338 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 83 datasets.
Click the + buttons to view associations for RXFP2 from the datasets below.
If available, associations are ranked by standardized value
Dataset | Summary | |
---|---|---|
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles | tissues with high or low expression of RXFP2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset. | |
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of RXFP2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of RXFP2 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 RXFP2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of RXFP2 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 RXFP2 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 RXFP2 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
ChEA Transcription Factor Targets | transcription factors binding the promoter of RXFP2 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 RXFP2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
ClinVar Gene-Phenotype Associations | phenotypes associated with RXFP2 gene from the curated ClinVar Gene-Phenotype Associations dataset. | |
COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing RXFP2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with RXFP2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with RXFP2 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 RXFP2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
COSMIC Cell Line Gene Mutation Profiles | cell lines with RXFP2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
CTD Gene-Disease Associations | diseases associated with RXFP2 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
DepMap CRISPR Gene Dependency | cell lines with fitness changed by RXFP2 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 RXFP2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with RXFP2 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 RXFP2 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 RXFP2 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 RXFP2 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 RXFP2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
ENCODE Transcription Factor Targets | transcription factors binding the promoter of RXFP2 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 RXFP2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
GAD Gene-Disease Associations | diseases associated with RXFP2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
GAD High Level Gene-Disease Associations | diseases associated with RXFP2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
GeneRIF Biological Term Annotations | biological terms co-occuring with RXFP2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing RXFP2 from the GeneSigDB Published Gene Signatures dataset. | |
GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of RXFP2 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 RXFP2 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 RXFP2 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 RXFP2 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of RXFP2 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
GO Biological Process Annotations 2015 | biological processes involving RXFP2 gene from the curated GO Biological Process Annotations 2015 dataset. | |
GO Biological Process Annotations 2025 | biological processes involving RXFP2 gene from the curated GO Biological Process Annotations2025 dataset. | |
GO Cellular Component Annotations 2015 | cellular components containing RXFP2 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
GO Molecular Function Annotations 2015 | molecular functions performed by RXFP2 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
GO Molecular Function Annotations 2025 | molecular functions performed by RXFP2 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
GTEx eQTL 2025 | SNPs regulating expression of RXFP2 gene from the GTEx eQTL 2025 dataset. | |
GTEx Tissue Gene Expression Profiles | tissues with high or low expression of RXFP2 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 RXFP2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of RXFP2 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
Guide to Pharmacology Chemical Ligands of Receptors | ligands (chemical) binding RXFP2 receptor from the curated Guide to Pharmacology Chemical Ligands of Receptors dataset. | |
Guide to Pharmacology Protein Ligands of Receptors | ligands (protein) binding RXFP2 receptor from the curated Guide to Pharmacology Protein Ligands of Receptors dataset. | |
GWASdb SNP-Disease Associations | diseases associated with RXFP2 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
GWASdb SNP-Phenotype Associations | phenotypes associated with RXFP2 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of RXFP2 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
HMDB Metabolites of Enzymes | interacting metabolites for RXFP2 protein from the curated HMDB Metabolites of Enzymes dataset. | |
HPO Gene-Disease Associations | phenotypes associated with RXFP2 gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset. | |
HuBMAP ASCT+B Annotations | cell types associated with RXFP2 gene from the HuBMAP ASCT+B dataset. | |
HuBMAP ASCT+B Augmented with RNA-seq Coexpression | cell types associated with RXFP2 gene from the HuBMAP ASCT+B Augmented with RNA-seq Coexpression dataset. | |
HuBMAP Azimuth Cell Type Annotations | cell types associated with RXFP2 gene from the HuBMAP Azimuth Cell Type Annotations dataset. | |
HuGE Navigator Gene-Phenotype Associations | phenotypes associated with RXFP2 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by RXFP2 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
InterPro Predicted Protein Domain Annotations | protein domains predicted for RXFP2 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of RXFP2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
KEGG Pathways | pathways involving RXFP2 protein from the KEGG Pathways dataset. | |
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of RXFP2 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 RXFP2 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
LOCATE Curated Protein Localization Annotations | cellular components containing RXFP2 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset. | |
LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain RXFP2 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by RXFP2 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of RXFP2 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 RXFP2 gene mutations from the MPO Gene-Phenotype Associations dataset. | |
OMIM Gene-Disease Associations | phenotypes associated with RXFP2 gene from the curated OMIM Gene-Disease Associations dataset. | |
Pathway Commons Protein-Protein Interactions | interacting proteins for RXFP2 from the Pathway Commons Protein-Protein Interactions dataset. | |
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of RXFP2 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of RXFP2 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
PFOCR Pathway Figure Associations 2023 | pathways involving RXFP2 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
PFOCR Pathway Figure Associations 2024 | pathways involving RXFP2 protein from the Wikipathways PFOCR 2024 dataset. | |
Reactome Pathways 2014 | pathways involving RXFP2 protein from the Reactome Pathways dataset. | |
Reactome Pathways 2024 | pathways involving RXFP2 protein from the Reactome Pathways 2024 dataset. | |
Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at RXFP2 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of RXFP2 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of RXFP2 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of RXFP2 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of RXFP2 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 RXFP2 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 RXFP2 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 RXFP2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
WikiPathways Pathways 2014 | pathways involving RXFP2 protein from the Wikipathways Pathways 2014 dataset. | |
WikiPathways Pathways 2024 | pathways involving RXFP2 protein from the WikiPathways Pathways 2024 dataset. | |