Dhingani, NeelGuo, ConghuiPan, JieLi, QiWarner, NeilJardine, SashaLeung, GabriellaKotlarz, DanielGonzaga-Jauregui, ClaudiaKlein, ChristophSnapper, Scott B.Navas-López, Víctor ManuelMuise, Aleixo M.2022-08-052022-08-052020-10-29Dhingani N, Guo C, Pan J, Li Q, Warner N, Jardine S, et al. The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease. Sci Rep. 2020 Oct 29;10(1):18648http://hdl.handle.net/10668/3886Very early onset inflammatory bowel disease (VEOIBD) denotes children with onset of IBD before six years of age. A number of monogenic disorders are associated with VEOIBD including tetratricopeptide repeat domain 7A (TTC7A) deficiency. TTC7A-deficiency is characterized by apoptotic colitis in milder cases with severe intestinal atresia and immunodeficiency in cases with complete loss of protein. We used whole exome sequencing in a VEOIBD patient presenting with colitis characterized by colonic apoptosis and no identified known VEOIBD variants, to identify compound heterozygous deleterious variants in the Ubiquitin protein ligase E3 component N-recognin 5 (UBR5) gene. Functional studies demonstrated that UBR5 co-immunoprecipitates with the TTC7A and the UBR5 variants had reduced interaction between UBR5 and TTC7A. Together this implicates UBR5 in regulating TTC7A signaling in VEOIBD patients with apoptotic colitis.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/ChildAmino acid sequenceInflammatory bowel diseasesProtein bindingUbiquitin-protein ligasesColitisNiñoSecuencia de aminoácidosEnfermedades inflamatorias del intestinoUnión proteicaUbiquitina-proteína ligasasMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age Factors::Age of OnsetMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Amino Acid SequenceMedical Subject Headings::Persons::Persons::Age Groups::Child::Child, PreschoolMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel DiseasesMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Protein BindingMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::ProteinsSequence Homology, Amino AcidMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal TransductionMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Ligases::Ubiquitin-Protein Ligase Complexes::Ubiquitin-Protein LigasesMedical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colitisresearch article33122718open access10.1038/s41598-020-73482-62045-2322PMC7596066