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PubMed:28011069 JSONTXT 35 Projects

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Id Subject Object Predicate Lexical cue
T1 0-136 Sentence denotes Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants.
T1 0-136 Sentence denotes Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants.
T2 137-148 Sentence denotes BACKGROUND:
T2 137-148 Sentence denotes BACKGROUND:
T3 149-436 Sentence denotes Germline heterozygous mutations in human signal transducer and activator of transcription 1 (STAT1) can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases, or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis.
T3 149-436 Sentence denotes Germline heterozygous mutations in human signal transducer and activator of transcription 1 (STAT1) can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases, or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis.
T4 437-587 Sentence denotes LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil domain (CCD) and DNA-binding domain (DBD).
T4 437-587 Sentence denotes LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil domain (CCD) and DNA-binding domain (DBD).
T5 588-778 Sentence denotes Moreover, 6% of patients with chronic mucocutaneous candidiasis with a GOF STAT1 mutation have mycobacterial disease, obscuring the functional significance of the identified STAT1 mutations.
T5 588-778 Sentence denotes Moreover, 6% of patients with chronic mucocutaneous candidiasis with a GOF STAT1 mutation have mycobacterial disease, obscuring the functional significance of the identified STAT1 mutations.
T6 779-902 Sentence denotes Current computational approaches, such as combined annotation-dependent depletion, do not distinguish LOF and GOF variants.
T6 779-902 Sentence denotes Current computational approaches, such as combined annotation-dependent depletion, do not distinguish LOF and GOF variants.
T7 903-913 Sentence denotes OBJECTIVE:
T7 903-913 Sentence denotes OBJECTIVE:
T8 914-962 Sentence denotes We estimated variations in the CCD/DBD of STAT1.
T8 914-962 Sentence denotes We estimated variations in the CCD/DBD of STAT1.
T9 963-971 Sentence denotes METHODS:
T9 963-971 Sentence denotes METHODS:
T10 972-1137 Sentence denotes We mutagenized 342 individual wild-type amino acids in the CCD/DBD (45.6% of full-length STAT1) to alanine and tested the mutants for STAT1 transcriptional activity.
T10 972-1137 Sentence denotes We mutagenized 342 individual wild-type amino acids in the CCD/DBD (45.6% of full-length STAT1) to alanine and tested the mutants for STAT1 transcriptional activity.
T11 1138-1146 Sentence denotes RESULTS:
T11 1138-1146 Sentence denotes RESULTS:
T12 1147-1249 Sentence denotes Of these 342 mutants, 201 were neutral, 30 were LOF, and 111 were GOF mutations in a luciferase assay.
T12 1147-1249 Sentence denotes Of these 342 mutants, 201 were neutral, 30 were LOF, and 111 were GOF mutations in a luciferase assay.
T13 1250-1398 Sentence denotes This assay system correctly estimated all previously reported LOF mutations (100%) and slightly fewer GOF mutations (78.1%) in the CCD/DBD of STAT1.
T13 1250-1398 Sentence denotes This assay system correctly estimated all previously reported LOF mutations (100%) and slightly fewer GOF mutations (78.1%) in the CCD/DBD of STAT1.
T14 1399-1536 Sentence denotes We found that GOF alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer.
T14 1399-1536 Sentence denotes We found that GOF alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer.
T15 1537-1765 Sentence denotes This assay also precisely predicted the effect of 2 hypomorphic and dominant negative mutations, E157K and G250E, in the CCD of STAT1 that we found in 2 unrelated patients with Mendelian susceptibility to mycobacterial diseases.
T15 1537-1765 Sentence denotes This assay also precisely predicted the effect of 2 hypomorphic and dominant negative mutations, E157K and G250E, in the CCD of STAT1 that we found in 2 unrelated patients with Mendelian susceptibility to mycobacterial diseases.
T16 1766-1777 Sentence denotes CONCLUSION:
T16 1766-1777 Sentence denotes CONCLUSION:
T17 1778-2026 Sentence denotes The systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and the effect of heterozygous missense mutations in STAT1 identified in patients with severe infectious diseases, including mycobacterial and fungal diseases.
T17 1778-2026 Sentence denotes The systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and the effect of heterozygous missense mutations in STAT1 identified in patients with severe infectious diseases, including mycobacterial and fungal diseases.