Abstract
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Endosomes / metabolism
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Exodeoxyribonucleases / chemistry
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Exodeoxyribonucleases / genetics*
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Exodeoxyribonucleases / metabolism
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Frameshift Mutation
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Gene Frequency
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Genetic Predisposition to Disease
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Genotype
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HeLa Cells
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Humans
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Lupus Erythematosus, Cutaneous / enzymology
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Lupus Erythematosus, Cutaneous / genetics*
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Mutation*
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Mutation, Missense
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Phosphoproteins / chemistry
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Phosphoproteins / genetics*
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Phosphoproteins / metabolism
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Protein Structure, Tertiary
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
Substances
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3' Untranslated Regions
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Phosphoproteins
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Recombinant Proteins
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Green Fluorescent Proteins
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Exodeoxyribonucleases
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three prime repair exonuclease 1