title: Disease causing mutations in the TNF and TNFR superfamilies: Focus on molecular mechanisms driving disease.
abstract: The tumor necrosis factor (TNF) and TNF receptor (TNFR) superfamilies comprise multidomain proteins with diverse roles in cell activation, proliferation and cell death. These proteins play pivotal roles in the initiation, maintenance and termination of immune responses and have vital roles outside the immune system. The discovery and analysis of diseases associated with mutations in these families has revealed crucial mechanistic details of their normal functions. This review focuses on mutations causing four different diseases, which represent distinct pathological mechanisms that can exist within these superfamilies: autoimmune lymphoproliferative syndrome (ALPS; FAS mutations), common variable immunodeficiency (CVID; TACI mutations), tumor necrosis factor receptor associated periodic syndrome (TRAPS; TNFR1 mutations) and hypohidrotic ectodermal dysplasia (HED; EDA1/EDAR mutations). In particular, we highlight how mutations have revealed information about normal receptor-ligand function and how such studies might direct new therapeutic approaches.
authors: Protein Sciences, Catalyst Biosciences, 260 Littlefield Avenue, South San Francisco, CA 94080, USA.
authors: Adrian A
authors: AA
authors: Lobito
authors: Tanit L
authors: TL
authors: Gabriel
authors: Jan Paul
authors: JP
authors: Medema
authors: Fiona C
authors: FC
authors: Kimberley
mesh_terms: D056735:Autoimmune Lymphoproliferative Syndrome / Q000235:genetics* / Q000378:metabolism; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000378:metabolism; D053359:Ectodermal Dysplasia 3, Anhidrotic / Q000235:genetics* / Q000378:metabolism; D053339:Edar Receptor / Q000235:genetics; D005334:Fever; D056660:Hereditary Autoinflammatory Diseases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D005810:Multigene Family; D009154:Mutation; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics
chemical_list: C506008:EDAR protein, human; D053339:Edar Receptor; C491901:FAS protein, human; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor