Ask about this productRelated genes to: RAPGEF1 Blocking Peptide
- Gene:
- RAPGEF1 NIH gene
- Name:
- Rap guanine nucleotide exchange factor 1
- Previous symbol:
- GRF2
- Synonyms:
- C3G
- Chromosome:
- 9q34.13
- Locus Type:
- gene with protein product
- Date approved:
- 1994-12-13
- Date modifiied:
- 2016-10-05
Related products to: RAPGEF1 Blocking Peptide
Related articles to: RAPGEF1 Blocking Peptide
- Obsessive compulsive disorder (OCD) is significantly heritable, but only a fraction of the contributory genetic variation has been identified, and the molecular etiology involved remains obscure. Identifying rare contributory variants of large effect would be an important milestone in helping to elucidate the mechanisms involved. Analysis of densely affected pedigrees is a potentially useful strategy to bypass the sample size challenges of standard case-control approaches. Here we performed whole genome sequencing (WGS) of 25 individuals across two multiplex OCD pedigrees. We prioritised rare variants using a Bayesian inference approach which incorporates variant pathogenicity and co-segregation with OCD. In the first pedigree, we identified a highly deleterious missense variant in , carried by the majority of affected individuals. This gene is brain-expressed and has previously been implicated in panic disorder and internet addiction GWAS studies. In the second pedigree, we identified a large deletion of and a missense variant in , that perfectly co-segregated in a specific branch of the family: both genes have previously been implicated in OCD and autism. Both genes contribute to a protein interaction network including and which we had previously identified in a large Tourette Syndrome pedigree. Our analysis suggests that both energy homeostasis and downstream signalling from the post-synaptic density may both be important avenues for future research. - Source: PubMed
Publication date: 2026/04/22
Ormond CathalCap MathieuChang Yi-ChiehRyan NiamhChavira DeniseWilliams KyleGrant Jon EMathews CarolHeron Elizabeth ACorvin Aiden - - Source: PubMed
Publication date: 2026/04/25
Prasad TuhinaIyer SharadaD'silva SianMathew Reuben JSowpati Divya TejRadha VegesnaKumar Megha - C3G (RapGEF1) is a guanine nucleotide exchange factor that activates Rap1, a small GTPase implicated in hematologic malignancies. We previously showed that C3G GEF activity is self-repressed via its AIR (autoinhibitory region). A lymphoma-associated missense mutation (Y554H) disrupts this inhibition, resulting in constitutive activation. This study aims to investigate the consequences of C3G dysregulation in B-cell lymphoma. - Source: PubMed
Publication date: 2025/11/27
Morán-Vaquero AlbaHerranz ÓscarDávila-Hidalgo AnaRodríguez-Blázquez AntonioFernández-Infante CristinaGarcía-Tuñón IgnacioVuelta Elenavan der Meer FemkeMargadant CoertGuerrero Carmende Pereda José M - C3G (RapGEF1) regulates the biology of liver hepatic progenitor cells and hepatocarcinoma cells, but its role in hepatocytes remained unknown. Therefore, we generated a mouse model lacking C3G in hepatocytes (C3GKO), which showed liver damage as evidenced by increased fibrosis, liver macrophages and serum transaminases activity. Furthermore, impaired liver maturation was observed in C3GKO mice demonstrated by the low expression of hepatocyte specific proteins (i.e. HNF4α), but higher levels of Alpha-fetoprotein, and stemness markers (i.e. CD133). Glucose homeostasis was also altered in C3GKO mice, as well as insulin and glucagon effects on hepatocytes, which resulted in reduced serum glucose levels and an enhanced response to glucagon. In addition, the expression of several glycolytic and gluconeogenic enzymes, as well as the levels of the active form of Glycogen phosphorylase (PYGL), were upregulated in livers from C3GKO mice, being remarkable the increased Pyruvate kinase isoform 2 (PKM2) levels accompanied by higher serum lactate concentrations. An increased expression of the ketogenic enzyme 3-hydroxy 3-methylglutaryl-CoA (HMG) synthase (Hmgcs2) was also found in these livers in parallel to elevated blood levels of beta-hydroxy-butyrate. Moreover, the fasting response was enhanced in C3GKO mice as compared to wt animals. Hence, livers lacking C3G in hepatocytes showed a higher expression of gluconeogenic, lipogenic and ketogenic enzymes than livers from wt mice and enhanced ketogenesis. Mechanistically, data support a PTBP1-mediated upregulation of PKM2 expression in hepatocytes lacking C3G, which leads to enhanced glycolysis. Other metabolic alterations are likely due to the defective insulin signaling and the enhanced glucagon signaling through a cAMP-PKA-dependent mechanism. In summary, we have identified a novel role for C3G in the liver as a key mediator of hepatocyte differentiation and metabolic functions of hepatocytes. Hence, its absence leads to an immature phenotype and an altered response to insulin and glucagon, favoring glucagon actions. - Source: PubMed
Publication date: 2025/10/07
Palao NereaMancebo JaimeBaquero CristinaIniesta-González MinervaCueto-Remacha MateoRodrigo-Faus MaríaGutierrez-Uzquiza AlvaroBragado PalomaCuesta Ángel MSánchez AránzazuGuerrero CarmenPorras Almudena - Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by early-onset challenges in social communication, repetitive behaviors, and clinical diversity. ASD is a highly heritable disorder, however, the exact mechanism by which inherited variants contribute to ASD in multiplex families, where more than one affected individual within a family is presented, remains unclear. We aimed to identify inherited genes in patients with ASD in a family with two affected siblings using Whole Genome Sequencing (WGS). - Source: PubMed
Gholizadeh Mehdi AghaBehjati FarkhondehGarshasbi Masoud