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PDBsum entry 5hez
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Transferase/transferase inhibitor
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PDB id
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5hez
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References listed in PDB file
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Key reference
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Title
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Resolving tyk2 locus genotype-To-Phenotype differences in autoimmunity.
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Authors
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C.A.Dendrou,
A.Cortes,
L.Shipman,
H.G.Evans,
K.E.Attfield,
L.Jostins,
T.Barber,
G.Kaur,
S.B.Kuttikkatte,
O.A.Leach,
C.Desel,
S.L.Faergeman,
J.Cheeseman,
M.J.Neville,
S.Sawcer,
A.Compston,
A.R.Johnson,
C.Everett,
J.I.Bell,
F.Karpe,
M.Ultsch,
C.Eigenbrot,
G.Mcvean,
L.Fugger.
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Ref.
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Sci Transl Med, 2016,
8,
363ra149.
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PubMed id
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Abstract
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Thousands of genetic variants have been identified, which contribute to the
development of complex diseases, but determining how to elucidate their
biological consequences for translation into clinical benefit is challenging.
Conflicting evidence regarding the functional impact of genetic variants in the
tyrosine kinase 2 (TYK2) gene, which is differentially associated with common
autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic
target. We aimed to resolve this conflict by performing genetic meta-analysis
across disorders; subsequent molecular, cellular, in vivo, and structural
functional follow-up; and epidemiological studies. Our data revealed a
protective homozygous effect that defined a signaling optimum between
autoimmunity and immunodeficiency and identified TYK2 as a potential drug target
for certain common autoimmune disorders.
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