RAPGEF5 Gene

Name	Rap guanine nucleotide exchange factor (GEF) 5
Description	Members of the RAS (see HRAS; MIM 190020) subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF5, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation (Rebhun et al., 2000 [PubMed 10934204]).[supplied by OMIM, Mar 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA large body of work has detailed the critical role of the interleukin‐18 pathway—especially the inhibitory actions of IL-18 binding protein (IL-18BP)—in modulating inflammatory and immune responses in a variety of disorders, including autoimmune arthritis, multiple sclerosis, ischemia/reperfusion injury, vascular disease, asthma, and experimental autoimmune encephalomyelitis. In these studies, IL-18BP administration consistently ameliorated tissue damage and inflammation by reducing proinflammatory cytokine production, suppressing Th17 differentiation, and rebalancing immune cell populations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " Moreover, targeted delivery of IL-18BP was shown to reprogram T cell responses and protect against neuroinflammation and tissue injury by overcoming unfavorable cytokine milieus."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWhile these studies underscore the importance of cytokine regulation in inflammatory and autoimmune contexts, emerging evidence is beginning to elucidate a distinct role for RAPGEF5—specifically through circular RNA isoforms derived from this gene—in cancer biology. In intrahepatic cholangiocarcinoma, investigations into circular RNAs and post‐translational modifications such as SUMOylation hint at novel regulatory networks that may converge on RAPGEF5-mediated signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " This line of research has further expanded with reports demonstrating that circRAPGEF5 is upregulated in bladder cancer, where it contributes to malignant progression and could serve as a potential biomarker or therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSimilarly, studies in colorectal cancer have begun to delineate the oncogenic functions of circRAPGEF5, suggesting that its dysregulation may perturb intracellular signaling pathways that control cell proliferation, migration, and survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Collectively, these findings point to a dual context where, on one side, cytokine inhibitors such as IL-18BP fine-tune immune responses to prevent tissue injury, while on the other, aberrant RNA species derived from RAPGEF5 emerge as important mediators in tumorigenesis. This expanding knowledge base implicates RAPGEF5—and particularly its circular RNA forms—as novel players at the intersection of cellular signaling and oncogenesis, underscoring their potential as targets in cancer therapy.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nirmal K Banda, Andrea Vondracek, Damian Kraus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanisms of inhibition of collagen-induced arthritis by murine IL-18 binding protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.170.4.2100"}], "href": "https://doi.org/10.4049/jimmunol.170.4.2100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12574381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12574381"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jason M Millward, Morten Løbner, Rachel D Wheeler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inflammation in the central nervous system and Th17 responses are inhibited by IFN-gamma-Induced IL-18 binding protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0902153"}], "href": "https://doi.org/10.4049/jimmunol.0902153"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20644165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20644165"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Haifeng Gu, Minghua Xie, Liqian Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The protective role of interleukin-18 binding protein in a murine model of cardiac ischemia/reperfusion injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transpl Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/tri.12683"}], "href": "https://doi.org/10.1111/tri.12683"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26340315"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26340315"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jian-Ming Li, Mohammad H Eslami, Michael J Rohrer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin 18 binding protein (IL18-BP) inhibits neointimal hyperplasia after balloon injury in an atherosclerotic rabbit model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Vasc Surg (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jvs.2007.12.005"}], "href": "https://doi.org/10.1016/j.jvs.2007.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18455646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18455646"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Huiyun Zhang, Junling Wang, Ling Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of IL-18 in atopic asthma is determined by balance of IL-18/IL-18BP/IL-18R."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.13323"}], "href": "https://doi.org/10.1111/jcmm.13323"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28922563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28922563"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sagie Schif-Zuck, Juergen Westermann, Nir Netzer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted overexpression of IL-18 binding protein at the central nervous system overrides flexibility in functional polarization of antigen-specific Th2 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.174.7.4307"}], "href": "https://doi.org/10.4049/jimmunol.174.7.4307"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15778395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15778395"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mathilde Harel, Charlotte Girard-Guyonvarc'h, Emiliana Rodriguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Production of IL-18 Binding Protein by Radiosensitive and Radioresistant Cells in CpG-Induced Macrophage Activation Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.2000168"}], "href": "https://doi.org/10.4049/jimmunol.2000168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32651219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32651219"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Li-Ming Zhang, Jun Zhang, Ying Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin-18 binding protein attenuates lipopolysaccharide-induced acute lung injury in mice via suppression NF-κB and activation Nrf2 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.09.193"}], "href": "https://doi.org/10.1016/j.bbrc.2018.09.193"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30301527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30301527"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mahmoud Abu Elhija, Eitan Lunenfeld, Luba Persky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Constitutive expression of IL-18 binding protein in murine testicular tissues and cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Cytokine Netw (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1684/ecn.2008.0117"}], "href": "https://doi.org/10.1684/ecn.2008.0117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18299271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18299271"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Mathilde Harel, Sébastien Fauteux-Daniel, Emiliana Rodriguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IL-18 Binding Protein-Producing Cells Attenuate Anemia in Murine Macrophage Activation Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.2300065"}], "href": "https://doi.org/10.4049/jimmunol.2300065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37074208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37074208"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Junhao Zheng, Yali Wang, Liye Tao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circ-RAPGEF5 promotes intrahepatic cholangiocarcinoma progression by stabilizing SAE1 to facilitate SUMOylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-023-02813-y"}], "href": "https://doi.org/10.1186/s13046-023-02813-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37705041"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37705041"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Chao Wang, Xianxu Yang "}, {"type": "b", "children": [{"type": "t", "text": "CircRAPGEF5 sponges miR-582-3p and targets KIF3A to regulate bladder cancer cell proliferation, migration and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunopharmacol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.intimp.2024.111613"}], "href": "https://doi.org/10.1016/j.intimp.2024.111613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38489970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38489970"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Duo Cheng, Feifei Chu, Fang Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of circ-RAPGEF5 inhibits colorectal cancer progression by reducing the expression of polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Toxicol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/tox.24278"}], "href": "https://doi.org/10.1002/tox.24278"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38775215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38775215"}]}]}]}
Synonyms	GFR, REPAC, MR-GEF
Proteins	RPGF5_HUMAN
NCBI Gene ID	9771
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RAPGEF5 has 6,954 functional associations with biological entities spanning 9 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, sequence feature) extracted from 106 datasets.

Click the + buttons to view associations for RAPGEF5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RAPGEF5 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RAPGEF5 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 RAPGEF5 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 RAPGEF5 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 RAPGEF5 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 RAPGEF5 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 RAPGEF5 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 RAPGEF5 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 RAPGEF5 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 RAPGEF5 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 RAPGEF5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RAPGEF5 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RAPGEF5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RAPGEF5 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 RAPGEF5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RAPGEF5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RAPGEF5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RAPGEF5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RAPGEF5 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 RAPGEF5 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 RAPGEF5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RAPGEF5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RAPGEF5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RAPGEF5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with RAPGEF5 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RAPGEF5 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by RAPGEF5 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 RAPGEF5 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 RAPGEF5 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 RAPGEF5 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 RAPGEF5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RAPGEF5 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 RAPGEF5 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 RAPGEF5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RAPGEF5 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 RAPGEF5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with RAPGEF5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of RAPGEF5 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 RAPGEF5 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of RAPGEF5 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 RAPGEF5 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.