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sentences

Id Subject Object Predicate Lexical cue
T1 0-147 Sentence denotes Cantu syndrome-associated SUR2 (ABCC9) mutations in distinct structural domains result in KATP channel gain-of-function by differential mechanisms.
T2 148-359 Sentence denotes The complex disorder Cantu syndrome (CS) arises from gain-of-function mutations in either KCNJ8 or ABCC9, the genes encoding the Kir6.1 and SUR2 subunits of ATP-sensitive potassium (KATP) channels, respectively.
T3 360-467 Sentence denotes Recent reports indicate that such mutations can increase channel activity by multiple molecular mechanisms.
T4 468-699 Sentence denotes In this study, we determined the mechanism by which KATP function is altered by several substitutions in distinct structural domains of SUR2: D207E in the intracellular L0-linker and Y985S, G989E, M1060I, and R1154Q/R1154W in TMD2.
T5 700-944 Sentence denotes We engineered substitutions at their equivalent positions in rat SUR2A (D207E, Y981S, G985E, M1056I, and R1150Q/R1150W) and investigated functional consequences using macroscopic rubidium (86Rb+) efflux assays and patch-clamp electrophysiology.
T6 945-1180 Sentence denotes Our results indicate that D207E increases KATP channel activity by increasing intrinsic stability of the open state, whereas the cluster of Y981S/G985E/M1056I substitutions, as well as R1150Q/R1150W, augmented Mg-nucleotide activation.
T7 1181-1325 Sentence denotes We also tested the responses of these channel variants to inhibition by the sulfonylurea drug glibenclamide, a potential pharmacotherapy for CS.
T8 1326-1437 Sentence denotes None of the D207E, Y981S, G985E, or M1056I substitutions had a significant effect on glibenclamide sensitivity.
T9 1438-1530 Sentence denotes However, Gln and Trp substitution at Arg-1150 significantly decreased glibenclamide potency.
T10 1531-1668 Sentence denotes In summary, these results provide additional confirmation that mutations in CS-associated SUR2 mutations result in KATP gain-of-function.
T11 1669-1902 Sentence denotes They help link CS genotypes to phenotypes and shed light on the underlying molecular mechanisms, including consequences for inhibitory drug sensitivity, insights that may inform the development of therapeutic approaches to manage CS.

kaiyin_test

Id Subject Object Predicate Lexical cue
T1 32-37 Gene denotes ABCC9
T2 39-48 Var denotes mutations
T3 90-102 MPA denotes KATP channel
T4 103-119 PosReg denotes gain-of-function
T5 169-183 Disease denotes Cantu syndrome
T6 201-217 PosReg denotes gain-of-function
T7 218-227 Var denotes mutations
T8 238-243 Gene denotes KCNJ8
T9 247-252 Gene denotes ABCC9
T10 394-403 Var denotes mutations
T11 408-416 PosReg denotes increase
T12 417-433 MPA denotes channel activity
T20 520-533 MPA denotes KATP function
T21 537-544 Reg denotes altered
T13 604-608 Gene denotes SUR2
T14 610-615 Var denotes D207E
T15 651-656 Var denotes Y985S
T16 658-663 Var denotes G989E
T17 665-671 Var denotes M1060I
T18 677-683 Var denotes R1154Q
T19 684-690 Var denotes R1154W
T22 971-976 Var denotes D207E
T23 977-986 PosReg denotes increases
T24 987-1008 MPA denotes KATP channel activity
T25 1012-1022 PosReg denotes increasing
T26 1023-1060 MPA denotes intrinsic stability of the open state
T28 1085-1090 Var denotes Y981S
T29 1091-1096 Var denotes G985E
T30 1097-1103 Var denotes M1056I
T31 1130-1136 Var denotes R1150Q
T32 1137-1143 Var denotes R1150W
T33 1145-1154 PosReg denotes augmented
T27 1155-1179 MPA denotes Mg-nucleotide activation
R1 T1 T2 ThemeOf ABCC9,mutations
R10 T12 T11 ThemeOf channel activity,increase
R11 T10 T11 CauseOf mutations,increase
R12 T13 T14 ThemeOf SUR2,D207E
R13 T13 T15 ThemeOf SUR2,Y985S
R14 T13 T16 ThemeOf SUR2,G989E
R15 T13 T17 ThemeOf SUR2,M1060I
R16 T13 T18 ThemeOf SUR2,R1154Q
R17 T13 T19 ThemeOf SUR2,R1154W
R18 T19 T21 CauseOf R1154W,altered
R19 T18 T21 CauseOf R1154Q,altered
R2 T2 T4 CauseOf mutations,gain-of-function
R20 T15 T21 CauseOf Y985S,altered
R21 T16 T21 CauseOf G989E,altered
R22 T17 T21 CauseOf M1060I,altered
R23 T20 T21 ThemeOf KATP function,altered
R24 T22 T25 CauseOf D207E,increasing
R25 T26 T25 ThemeOf intrinsic stability of the open state,increasing
R26 T25 T23 CauseOf increasing,increases
R27 T24 T23 ThemeOf KATP channel activity,increases
R28 T28 T33 CauseOf Y981S,augmented
R29 T29 T33 CauseOf G985E,augmented
R3 T3 T4 ThemeOf KATP channel,gain-of-function
R30 T30 T33 CauseOf M1056I,augmented
R31 T31 T33 CauseOf R1150Q,augmented
R32 T32 T33 CauseOf R1150W,augmented
R33 T27 T33 ThemeOf Mg-nucleotide activation,augmented
R4 T8 T7 ThemeOf KCNJ8,mutations
R5 T9 T7 ThemeOf ABCC9,mutations
R6 T5 T6 ThemeOf Cantu syndrome,gain-of-function
R7 T7 T6 CauseOf mutations,gain-of-function
R8 T8 T10 ThemeOf KCNJ8,mutations
R9 T9 T10 ThemeOf ABCC9,mutations

name_no

Id Subject Object Predicate Lexical cue
T1 32-37 Gene denotes ABCC9
T2 39-48 Var denotes mutations
T3 90-102 MPA denotes KATP channel
T4 103-119 PosReg denotes gain-of-function
T5 169-183 Disease denotes Cantu syndrome
T6 201-217 PosReg denotes gain-of-function
T7 218-227 Var denotes mutations
T8 238-243 Gene denotes KCNJ8
T9 247-252 Gene denotes ABCC9
T10 394-403 Var denotes mutations
T11 408-416 PosReg denotes increase
T12 417-433 MPA denotes channel activity
T20 520-533 MPA denotes KATP function
T21 537-544 Reg denotes altered
T13 604-608 Gene denotes SUR2
T14 610-615 Var denotes D207E
T15 651-656 Var denotes Y985S
T16 658-663 Var denotes G989E
T17 665-671 Var denotes M1060I
T18 677-683 Var denotes R1154Q
T19 684-690 Var denotes R1154W
T22 971-976 Var denotes D207E
T23 977-986 PosReg denotes increases
T24 987-1008 MPA denotes KATP channel activity
T25 1012-1022 PosReg denotes increasing
T26 1023-1060 MPA denotes intrinsic stability of the open state
T28 1085-1090 Var denotes Y981S
T29 1091-1096 Var denotes G985E
T30 1097-1103 Var denotes M1056I
T31 1130-1136 Var denotes R1150Q
T32 1137-1143 Var denotes R1150W
T33 1145-1154 PosReg denotes augmented
T27 1155-1179 MPA denotes Mg-nucleotide activation
R1 T1 T2 ThemeOf ABCC9,mutations
R10 T12 T11 ThemeOf channel activity,increase
R11 T10 T11 CauseOf mutations,increase
R12 T13 T14 ThemeOf SUR2,D207E
R13 T13 T15 ThemeOf SUR2,Y985S
R14 T13 T16 ThemeOf SUR2,G989E
R15 T13 T17 ThemeOf SUR2,M1060I
R16 T13 T18 ThemeOf SUR2,R1154Q
R17 T13 T19 ThemeOf SUR2,R1154W
R18 T19 T21 CauseOf R1154W,altered
R19 T18 T21 CauseOf R1154Q,altered
R2 T2 T4 CauseOf mutations,gain-of-function
R20 T15 T21 CauseOf Y985S,altered
R21 T16 T21 CauseOf G989E,altered
R22 T17 T21 CauseOf M1060I,altered
R23 T20 T21 ThemeOf KATP function,altered
R24 T22 T25 CauseOf D207E,increasing
R25 T26 T25 ThemeOf intrinsic stability of the open state,increasing
R26 T25 T23 CauseOf increasing,increases
R27 T24 T23 ThemeOf KATP channel activity,increases
R28 T28 T33 CauseOf Y981S,augmented
R29 T29 T33 CauseOf G985E,augmented
R3 T3 T4 ThemeOf KATP channel,gain-of-function
R30 T30 T33 CauseOf M1056I,augmented
R31 T31 T33 CauseOf R1150Q,augmented
R32 T32 T33 CauseOf R1150W,augmented
R33 T27 T33 ThemeOf Mg-nucleotide activation,augmented
R4 T8 T7 ThemeOf KCNJ8,mutations
R5 T9 T7 ThemeOf ABCC9,mutations
R6 T5 T6 ThemeOf Cantu syndrome,gain-of-function
R7 T7 T6 CauseOf mutations,gain-of-function
R8 T8 T10 ThemeOf KCNJ8,mutations
R9 T9 T10 ThemeOf ABCC9,mutations

mondo_disease

Id Subject Object Predicate Lexical cue mondo_id
T1 0-14 Disease denotes Cantu syndrome http://purl.obolibrary.org/obo/MONDO_0009406
T2 169-183 Disease denotes Cantu syndrome http://purl.obolibrary.org/obo/MONDO_0009406
T3 185-187 Disease denotes CS http://purl.obolibrary.org/obo/MONDO_0009406
T4 1322-1324 Disease denotes CS http://purl.obolibrary.org/obo/MONDO_0009406
T5 1607-1609 Disease denotes CS http://purl.obolibrary.org/obo/MONDO_0009406
T6 1684-1686 Disease denotes CS http://purl.obolibrary.org/obo/MONDO_0009406
T7 1899-1901 Disease denotes CS http://purl.obolibrary.org/obo/MONDO_0009406

NCBITAXON

Id Subject Object Predicate Lexical cue db_id
T1 761-764 OrganismTaxon denotes rat 10114|10116

Anatomy-UBERON

Id Subject Object Predicate Lexical cue uberon_id
T1 623-636 Body_part denotes intracellular http://purl.obolibrary.org/obo/GO_0005622