RAPGEF1 Gene

Name	Rap guanine nucleotide exchange factor (GEF) 1
Description	This gene encodes a human guanine nucleotide exchange factor. It transduces signals from CRK by binding the SH3 domain of CRK, and activating several members of the Ras family of GTPases. This signaling cascade that may be involved in apoptosis, integrin-mediated signal transduction, and cell transformation. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nC3G (RAPGEF1) functions as a pivotal guanine nucleotide exchange factor for Rap1 and related Ras family GTPases to coordinate immune receptor signaling and cytoskeletal dynamics. In T lymphocytes, for example, it is recruited downstream of WAVE2 and the CrkL adaptor to mediate T cell receptor–stimulated integrin clustering and affinity maturation, while in macrophages and neutrophils it facilitates Fcγ receptor–dependent phagocytosis and localized integrin activation during chemotaxis, respectively."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "Disparate tumor models reveal that C3G exerts context‐dependent roles in oncogenesis and tumor progression. Under some conditions, overexpression of C3G suppresses Ras‐driven transformation—interfering with ERK phosphorylation and anchorage‐independent growth—whereas in other settings its gene amplification or epigenetic deregulation is linked to enhanced Rap1 activation, modulation of integrin function, and p38 MAPK signaling that promote cell migration, invasion, or apoptosis. In addition, deregulation of its autoinhibitory mechanisms and abnormal interactions with kinases (e.g. Hck) or adaptor proteins (e.g. Crkl) further illustrate its complex and sometimes opposing contributions to cancer cell differentiation and survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "15"}]}, {"type": "t", "text": "C3G is also indispensable for a range of differentiation and developmental processes. In neuroblastoma cells, activation of C3G by oncogenic receptor tyrosine kinases (e.g. ALK) stimulates Rap1‐mediated neurite outgrowth and influences proliferation. In the developing forebrain, its expression is under the control of Dlx transcription factors, and at the centrosome C3G regulates both centriole duplication and ciliary homeostasis. In muscle cells, interactions with kinases such as GSK3β and Akt are integral to promoting myogenic differentiation, while genetic mutations in RAPGEF1 are associated with neurodevelopmental defects in animal models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "20"}]}, {"type": "t", "text": "In metabolic signaling, RAPGEF1 participates in the insulin receptor–activated CAP/TC10 pathway that regulates Glut4 translocation, and genetic studies have linked RAPGEF1 polymorphisms to altered risk for type 2 diabetes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "Within the hematopoietic system, C3G contributes to megakaryocyte differentiation and platelet activation. Transgenic mouse models, in which either the wild‐type or GEF-deficient C3G is expressed under a platelet-specific promoter, demonstrate that its guanine nucleotide exchange activity modulates clotting responses and may have additional roles in neutrophil development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "Furthermore, in the epidermis, RAPGEF1 is targeted by microRNAs such as miR‑203. Down‐regulation of RAPGEF1 contributes to the balance between keratinocyte proliferation and differentiation, with potential implications in skin carcinogenesis and hyperproliferative disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wenying Zhang, Yuan Shao, Deyu Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M212671200"}], "href": "https://doi.org/10.1074/jbc.M212671200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12697763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12697763"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jeffrey C Nolz, Lucas P Nacusi, Colin M Segovis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200801121"}], "href": "https://doi.org/10.1083/jcb.200801121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18809728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18809728"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jooho Chung, Carlos H Serezani, Steven K Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rap1 activation is required for Fc gamma receptor-dependent phagocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.181.8.5501"}], "href": "https://doi.org/10.4049/jimmunol.181.8.5501"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18832707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18832707"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuan He, Ashish Kapoor, Sara Cook, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL-C3G complex and activating Rap1 at the leading edge."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.078535"}], "href": "https://doi.org/10.1242/jcs.078535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21628423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21628423"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "R Shivakrupa, Vegesna Radha, Ch Sudhakar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M310656200"}], "href": "https://doi.org/10.1074/jbc.M310656200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14551197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14551197"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Carmen Guerrero, Susana Martín-Encabo, Alberto Fernández-Medarde, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C3G-mediated suppression of oncogene-induced focus formation in fibroblasts involves inhibition of ERK activation, cyclin A expression and alterations of anchorage-independent growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1207622"}], "href": "https://doi.org/10.1038/sj.onc.1207622"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15077165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15077165"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tomomi Hirata, Hisaki Nagai, Kiyoshi Koizumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amplification, up-regulation and over-expression of C3G (CRK SH3 domain-binding guanine nucleotide-releasing factor) in non-small cell lung cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10038-004-0148-1"}], "href": "https://doi.org/10.1007/s10038-004-0148-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15138850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15138850"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Vegesna Radha, Ajumeera Rajanna, Ghanshyam Swarup "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylated guanine nucleotide exchange factor C3G, induced by pervanadate and Src family kinases localizes to the Golgi and subcortical actin cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2121-5-31"}], "href": "https://doi.org/10.1186/1471-2121-5-31"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15320955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15320955"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "K Okino, H Nagai, H Nakayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inactivation of Crk SH3 domain-binding guanine nucleotide-releasing factor (C3G) in cervical squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Gynecol Cancer (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1525-1438.2006.00352.x"}], "href": "https://doi.org/10.1111/j.1525-1438.2006.00352.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16681758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16681758"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Susana Martín-Encabo, Eugenio Santos, Carmen Guerrero "}, {"type": "b", "children": [{"type": "t", "text": "C3G mediated suppression of malignant transformation involves activation of PP2A phosphatases at the subcortical actin cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2007.07.036"}], "href": "https://doi.org/10.1016/j.yexcr.2007.07.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17825818"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17825818"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Vera Maia, María Sanz, Javier Gutierrez-Berzal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C3G silencing enhances STI-571-induced apoptosis in CML cells through p38 MAPK activation, but it antagonizes STI-571 inhibitory effect on survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2009.03.015"}], "href": "https://doi.org/10.1016/j.cellsig.2009.03.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19324082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19324082"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Kunal Dayma, Vegesna Radha "}, {"type": "b", "children": [{"type": "t", "text": "Cytoskeletal remodeling by C3G to induce neurite-like extensions and inhibit motility in highly invasive breast carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2011.01.004"}], "href": "https://doi.org/10.1016/j.bbamcr.2011.01.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21223981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21223981"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Neibla Priego, María Arechederra, Celia Sequera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C3G knock-down enhances migration and invasion by increasing Rap1-mediated p38α activation, while it impairs tumor growth through p38α-independent mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.9911"}], "href": "https://doi.org/10.18632/oncotarget.9911"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27286263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27286263"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Arturo Carabias, María Gómez-Hernández, Sergio de Cima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanisms of autoregulation of C3G, activator of the GTPase Rap1, and its catalytic deregulation in lymphomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.abb7075"}], "href": "https://doi.org/10.1126/scisignal.abb7075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32873726"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32873726"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Livia Pagano, Francesca Malagrinò, Caterina Nardella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Experimental Characterization of the Interaction between the N-Terminal SH3 Domain of Crkl and C3G."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms222413174"}], "href": "https://doi.org/10.3390/ijms222413174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34947971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34947971"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "C Schönherr, H-L Yang, M Vigny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2010.27"}], "href": "https://doi.org/10.1038/onc.2010.27"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20190816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20190816"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Angela Bithell, Tony Hsu, Apsara Kandanearatchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0010392"}], "href": "https://doi.org/10.1371/journal.pone.0010392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20436929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20436929"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Sanjeev Chavan Nayak, Vegesna Radha "}, {"type": "b", "children": [{"type": "t", "text": "C3G localizes to the mother centriole in a cenexin-dependent manner and regulates centrosome duplication and primary cilium length."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.243113"}], "href": "https://doi.org/10.1242/jcs.243113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32371504"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32371504"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Divya Sriram, Kunal Dayma, Ambure Sharada Devi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Complex formation and reciprocal regulation between GSK3β and C3G."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2021.118964"}], "href": "https://doi.org/10.1016/j.bbamcr.2021.118964"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33450305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33450305"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Na Li, Pei Zhou, Miaomiao Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zebrafish modeling mimics developmental phenotype of patients with RAPGEF1 mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13965"}], "href": "https://doi.org/10.1111/cge.13965"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33834495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33834495"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Kyung-Won Hong, Hyun-Seok Jin, Ji-Eun Lim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RAPGEF1 gene variants associated with type 2 diabetes in the Korean population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Res Clin Pract (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.diabres.2009.02.019"}], "href": "https://doi.org/10.1016/j.diabres.2009.02.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19297053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19297053"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Lili Qu, Bangshun He, Yuqin Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between polymorphisms in RAPGEF1, TP53, NRF1 and type 2 diabetes in Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Res Clin Pract (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.diabres.2010.11.019"}], "href": "https://doi.org/10.1016/j.diabres.2010.11.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21146886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21146886"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Sara Ortiz-Rivero, Cristina Baquero, Luis Hernández-Cano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C3G, through its GEF activity, induces megakaryocytic differentiation and proplatelet formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Commun Signal (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12964-018-0311-5"}], "href": "https://doi.org/10.1186/s12964-018-0311-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30567575"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30567575"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Sara Gutiérrez-Herrero, Vera Maia, Javier Gutiérrez-Berzal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C3G transgenic mouse models with specific expression in platelets reveal a new role for C3G in platelet clotting through its GEF activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2012.05.021"}], "href": "https://doi.org/10.1016/j.bbamcr.2012.05.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22659131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22659131"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Christelle Golebiewski, Cécile Gastaldi, Diane-Lore Vieu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and functional validation of SRC and RAPGEF1 as new direct targets of miR-203, involved in regulation of epidermal homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-023-40441-w"}], "href": "https://doi.org/10.1038/s41598-023-40441-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37635193"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37635193"}]}]}]}
Synonyms	C3G, GRF2
Proteins	RPGF1_HUMAN
NCBI Gene ID	2889
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RAPGEF1 has 6,560 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 131 datasets.

Click the + buttons to view associations for RAPGEF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RAPGEF1 Gene

Functional Associations

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	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by RAPGEF1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RAPGEF1 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 RAPGEF1 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 RAPGEF1 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 RAPGEF1 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 RAPGEF1 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 RAPGEF1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving RAPGEF1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of RAPGEF1 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 RAPGEF1 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 RAPGEF1 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 RAPGEF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RAPGEF1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RAPGEF1 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 RAPGEF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RAPGEF1 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 RAPGEF1 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 RAPGEF1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RAPGEF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RAPGEF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RAPGEF1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RAPGEF1 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 RAPGEF1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing RAPGEF1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RAPGEF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RAPGEF1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RAPGEF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RAPGEF1 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 RAPGEF1 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 RAPGEF1 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 RAPGEF1 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 RAPGEF1 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 RAPGEF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RAPGEF1 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 RAPGEF1 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 RAPGEF1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RAPGEF1 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 RAPGEF1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with RAPGEF1 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 RAPGEF1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.