Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant.
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.
Vang
Torkel
T
Program on Inflammatory Disease Research, Infectious and Inflammatory Disease Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Congia
Mauro
M
Macis
Maria Doloretta
MD
Musumeci
Lucia
L
Orrú
Valeria
V
Zavattari
Patrizia
P
Nika
Konstantina
K
Tautz
Lutz
L
Taskén
Kjetil
K
Cucca
Francesco
F
Mustelin
Tomas
T
Bottini
Nunzio
N
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*
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