title: Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant.
abstract: A SNP in the gene PTPN22 is associated with type 1 diabetes, rheumatoid arthritis, lupus, Graves thyroiditis, Addison disease and other autoimmune disorders. T cells from carriers of the predisposing allele produce less interleukin-2 upon TCR stimulation, and the encoded phosphatase has higher catalytic activity and is a more potent negative regulator of T lymphocyte activation. We conclude that the autoimmune-predisposing allele is a gain-of-function mutant.
authors.affiliation: Program on Inflammatory Disease Research, Infectious and Inflammatory Disease Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Torkel
authors.initials: T
authors.lastname: Vang
authors.forename: Mauro
authors.initials: M
authors.lastname: Congia
authors.forename: Maria Doloretta
authors.initials: MD
authors.lastname: Macis
authors.forename: Lucia
authors.initials: L
authors.lastname: Musumeci
authors.forename: Valeria
authors.initials: V
authors.lastname: Orrú
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zavattari
authors.forename: Konstantina
authors.initials: K
authors.lastname: Nika
authors.forename: Lutz
authors.initials: L
authors.lastname: Tautz
authors.forename: Kjetil
authors.initials: K
authors.lastname: Taskén
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucca
authors.forename: Tomas
authors.initials: T
authors.lastname: Mustelin
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
mesh_terms: D000483:Alleles; D000906:Antibodies / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D002384:Catalysis; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007558:Italy; D008213:Lymphocyte Activation; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
chemical_list: D000906:Antibodies; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases