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test-210614

Id Subject Object Predicate Lexical cue proteinmutation
28011069_0 1644-1649 ProteinMutation denotes G250E rs1375555193

PubTator4TogoVar

Id Subject Object Predicate Lexical cue proteinmutation
28011069_0 1644-1649 ProteinMutation denotes G250E rs1375555193

Inflammaging

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.
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.
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.
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:
T8 914-962 Sentence denotes We estimated variations in the CCD/DBD of STAT1.
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.
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.
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.
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:
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.
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:
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).
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.
T7 903-913 Sentence denotes OBJECTIVE:
T8 914-962 Sentence denotes We estimated variations in the CCD/DBD of STAT1.
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.
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.
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.
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:
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.

kaiyin_test

Id Subject Object Predicate Lexical cue
T1 149-180 Var denotes Germline heterozygous mutations
T2 190-207 Gene denotes signal transducer
T3 212-240 Gene denotes activator of transcription 1
T4 259-275 NegReg denotes loss of function
T5 331-353 Disease denotes mycobacterial diseases
T6 358-374 PosReg denotes gain of function
T7 402-435 Disease denotes chronic mucocutaneous candidiasis
T8 449-458 Var denotes mutations
T10 484-490 Reg denotes affect
T9 500-507 MPA denotes domains
T11 511-516 Gene denotes STAT1
T12 533-551 MPA denotes coiled-coil domain
T13 562-580 MPA denotes DNA-binding domain
R1 T1 T4 CauseOf Germline heterozygous mutations,loss of function
R10 T12 T9 ThemeOf coiled-coil domain,domains
R11 T13 T9 ThemeOf DNA-binding domain,domains
R2 T2 T1 ThemeOf signal transducer,Germline heterozygous mutations
R3 T1 T6 CauseOf Germline heterozygous mutations,gain of function
R4 T7 T6 ThemeOf chronic mucocutaneous candidiasis,gain of function
R5 T5 T4 ThemeOf mycobacterial diseases,loss of function
R6 T3 T1 ThemeOf activator of transcription 1,Germline heterozygous mutations
R7 T8 T10 CauseOf mutations,affect
R8 T9 T10 ThemeOf domains,affect
R9 T11 T9 ThemeOf STAT1,domains

name_no

Id Subject Object Predicate Lexical cue
T1 149-180 Var denotes Germline heterozygous mutations
T2 190-207 Gene denotes signal transducer
T3 212-240 Gene denotes activator of transcription 1
T4 259-275 NegReg denotes loss of function
T5 331-353 Disease denotes mycobacterial diseases
T6 358-374 PosReg denotes gain of function
T7 402-435 Disease denotes chronic mucocutaneous candidiasis
T8 449-458 Var denotes mutations
T10 484-490 Reg denotes affect
T9 500-507 MPA denotes domains
T11 511-516 Gene denotes STAT1
T12 533-551 MPA denotes coiled-coil domain
T13 562-580 MPA denotes DNA-binding domain
R1 T1 T4 CauseOf Germline heterozygous mutations,loss of function
R10 T12 T9 ThemeOf coiled-coil domain,domains
R11 T13 T9 ThemeOf DNA-binding domain,domains
R2 T2 T1 ThemeOf signal transducer,Germline heterozygous mutations
R3 T1 T6 CauseOf Germline heterozygous mutations,gain of function
R4 T7 T6 ThemeOf chronic mucocutaneous candidiasis,gain of function
R5 T5 T4 ThemeOf mycobacterial diseases,loss of function
R6 T3 T1 ThemeOf activator of transcription 1,Germline heterozygous mutations
R7 T8 T10 CauseOf mutations,affect
R8 T9 T10 ThemeOf domains,affect
R9 T11 T9 ThemeOf STAT1,domains