ライフサイエンスコーパス: gain-of-function

1 signaling in the fat body studying loss and gain of function.

2 ting the HSC phenotype associated with GATA1 gain of function.

3 ne the GluA2-A793F-CNIH3 complex expressed a gain of function.

4 oteins are toxic to cells independent of RNA gain of function.

5 und to be associated with a relatively small gain-of-function.

6 nesis independently of wild-type p53, termed gain-of-function.

7 CS-associated SUR2 mutations result in KATP gain-of-function.

8 dicted to enhance NOTCH2 stability and cause gain-of-function.

9 ng placed ABHD5 R299/G328 and R303/G332 from gain-of-function ABHD4 in close proximity on the ABHD pr

10 Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) p

11 nate PT domains, which resulted in the first gain-of-function ACP with improved interactions with its

12 n the CEL VNTR causes CP through proteotoxic gain-of-function activation of maladaptive cell signalin

13 f FUS nuclear levels and with putative toxic gain of function activities.

14 an important role in mediating mutant p53s' gain-of-function activities in HNSCCs.

15 TP53 missense mutations can also contribute gain-of-function activities that impact tumour progressi

16 LGG-associated IDH mutations confer gain-of-function activity by converting alpha-ketoglutar

17 mutated in a variety of cancers to confer a gain-of-function activity resulting in the accumulation

18 in maize was achieved through selection of a gain of function allele of the teosinte branched1 (tb1)

19 thway, through conditional expression of the gain-of-function alleles BrafV600E and KrasG12D in the d

20 skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome

21 Using a series of loss- and gain-of-function alleles to dial E2F transcriptional out

22 Ob homolog, HLA-DOB, revealed both loss- and gain-of-function alleles, which could affect the ability

23 s suggest that these mutations may behave as gain-of-function alleles.

24 Finally, FGF9/10 gain of function also resulted in extensive dendritogene

25 53) in 54% of tumors and transposon-mediated gain-of-function alterations in B-cell lymphoma-extra la

26 Most importantly, loss- and gain-of-function analyses provide solid evidence that Dm

27 e and therapeutic relevance of such effects (gain of function and dominant-negative activity) in lung

28 res are predominantly missense, leading to a gain of function and increased neuronal excitability.

29 se these altered properties may confer toxic gain of function and reflect differential propensity for

30 In contrast, mutant p53 gain of function and their associated vulnerabilities ca

31 Finally, both gain-of function and loss-of-function experiments reveal

32 haploinsufficiency (NHI) mechanisms, such as gain-of-function and dominant-negative mechanisms, are o

33 l substitution (TES148C), accounting for the gain-of-function and improved reaction kinetics.

34 Combining gain-of-function and loss-of-function approaches in an e

35 By using both gain-of-function and loss-of-function approaches, we dem

36 Examination of single and multiple gain-of-function and loss-of-function receptor mutants r

37 r of active and inactive splice variants, or gain-of-function and loss-of-function small nucleotide p

38 Gain-of-function and loss-of-function studies in colorec

39 om lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a spec

40 e studies on mutp53 protein accumulation and gain-of-function and targeted therapies for mutp53 in hu

41 Through loss-of-function, gain-of-function, and clinical-association studies, we i

42 entary DNA represents the most commonly used gain-of-function approach for interrogating gene functio

43 that could explain this block, we applied a gain-of-function approach using a PU.1/Spi-B-deficient p

44 Using a gain-of-function approach, we investigated the responses

45 Using conditional gain-of-function approaches in Xenopus and mouse to main

46 Using gain-of-function approaches, we found that overexpressio

47 and in IPF lung fibroblasts, using loss-and-gain of function assays, and in vivo using specific inhi

48 ected inflammatory mediators in cell culture gain-of-function assays.

49 Among the genetic gains of function associated with urinary E. coli isolat

50 investigated both loss-of-function and toxic gain-of-function astrocyte mechanisms that could play a

51 roprotein convertase subtilisin/kexin type 9 gain-of-function atherosclerosis model.

52 Our data demonstrate gain-of-function attributes at the channel level and dif

53 only on the effects of mutant p53 oncogenic gain of function but also on the mechanisms underlying n

54 Toxic gain-of-function by betaS has been linked to dysfunction

55 common mechanisms responsible for generating gain-of-function, cancer-causing alterations.

56 l integrity in homeostasis and diseases: (i) gain-of-function CdGAP mutants found in Adams-Oliver Syn

57 and isotope tracing experiments in loss- and gain-of-function cell and mouse models of Slc22a1, we un

58 lt in increased sodium channel activity with gain-of-function, characterized by slowing of fast inact

59 ysis in our Drosophila EA6 model stem from a gain-of-function chloride channelopathy of glial cells.

60 e unusual genetic behavior of a quantitative gain-of-function CNGC mutation (brush) in Lotus japonicu

61 itative analysis using a series of loss- and gain-of-function conditions shows that the ventral and l

62 This gain-of-function CRY1 variant causes reduced expression

63 e model with a naturally occurring WS-linked gain-of-function Cxcr4 mutation, we explored the possibi

64 Gain-of-function CXCR4 mutations that affect homologous

65 The pairing of both loss- and gain-of-function datasets reveals complex gene networks

66 FSHD is a gain-of-function disease characterized by the aberrant e

67 phosphorylation of delta-4E-BP1 may yield a gain of function, distinct from translation regulation,

68 Consistent with a gain-of-function effect, ectopic expression of the 2 ide

69 urocognitive and motor delay, via a proposed gain-of-function effect.

70 plitude reduction) in eight patients or only gain-of-function effects (hyperpolarizing shift of volta

71 nteraction domain, which supposedly mediates gain-of-function effects obtained through ectopic OPS ov

72 isease thought to be primarily caused by RNA gain-of-function effects.

73 idate mutant NADK, whose expression provides gain-of-function enzymatic activity leading to a reducti

74 ifferences in attractiveness between another gain-of-function ET receptor mutant, etr1-3, or the loss

75 enes manifest the opposite pattern, creating gain-of-function events.

76 human gut and as a general research tool for gain-of-function experiments (i.e., gavage of fecal pell

77 Using inducible gain-of-function experiments during embryonic stem cell

78 Gain-of-function experiments in human embryonic stem cel

79 Loss- and gain-of-function experiments in mice demonstrate that os

80 Loss- and gain-of-function experiments in zebrafish embryos demons

81 Finally, loss- and gain-of-function experiments indicated that the NP12-med

82 latory factor (NHERF)-1 loss-of-function and gain-of-function experiments reveal that polymerized act

83 Gain-of-function experiments show that it can potently i

84 Finally, gain-of-function experiments show that Pth4 can alter ca

85 genetic analyses using loss-of-function and gain-of-function experiments suggest that these transcri

86 Using inhibitor and gain-of-function experiments, we show that FGF signallin

87 reprogramming stages and performed loss- and gain-of-function experiments.

88 lude that SCA2 is a disease characterized by gain of function for ATXN2.

89 While it is common to suppress gain of function for chemotherapy, it remains challengin

90 This molecular axis reveals a specific gain of function for mutant p53 in the response to insul

91 lves a dominant negative effect and/or toxic gain of function for PHOX2B mutations.

92 he nonsense effects for the p.W240X, and (2) gain-of-function for the p.R384X, supported by the fourf

93 In principle, the inhibition of candidate gain-of-function genes defined through genomic analyses

94 esis supported by analysis of influenza in a gain-of-function genetic mouse model.

95 Paradoxically, gain-of-function GLRA1 mutations also cause hyperekplexi

96 y p53, and some endow the protein with novel gain of function (GOF) properties that actively promote

97 mulate in cancer cells and may confer unique gain-of-function (GOF) activities to promote tumorigenic

98 Using gain-of-function (GOF) and loss-of-function (LOF) approa

99 p53 often promotes tumor progression through gain-of-function (GOF) mechanisms.

100 UBE2C is transcriptionally activated by the gain-of-function (GOF) mutant p53, although it is transc

101 Gain-of-function (GOF) mutations affecting the coiled-co

102 Patients with STAT1 gain-of-function (GOF) mutations have increased viral su

103 Gain-of-function (GOF) mutations in the human signal tra

104 Gain-of-function (GOF) mutations of protein tyrosine pho

105 nodeficiencies, we detected 2 novel nonsense gain-of-function (GOF) NFKB2 mutations (E418X and R635X)

106 Gain-of-function (GOF) p53 mutations are observed freque

107 Some gain-of-function (GOF) p53 mutations endow tumor cells w

108 either a loss-of-function (LOF) mechanism, a gain-of-function (GOF) process, or both.

109 Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to met

110 Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that promote cancer ce

111 The ongoing moratorium on gain-of-function (GOF) research with highly pathogenic a

112 his pathway through a series of beta-catenin gain-of-function (GSK3 inhibition and beta-catenin overe

113 ancer cells differ from normal cells in both gain of functions (i.e., upregulation) and loss of funct

114 Gain-of-function IDH mutations are initiating events tha

115 N-nitrosourea-induced mutation that causes a gain of function in adenosine 5'-monophosphate deaminase

116 fore, we examined the effects of KCP loss or gain of function in mice that were maintained on either

117 primary embryonic retinal cultures and Dlx2 gain of function in utero strongly support that DLX2 is

118 The species-specific gain-of-function in antiviral immunity observed in ISG15

119 , we propose a dynamics-driven model for the gain-of-function in ENaC by alphaW493R.

120 ns as precursors for aggregation and adverse gain-of-function in human disease, there is yet little k

121 hesis that SCN1B-C121W confers a deleterious gain-of-function in human GEFS+ patients.

122 s Munc13-1-independent fusion and leads to a gain-of-function in rescue experiments in Caenorhabditis

123 nction, but instead results in a deleterious gain-of-function in the brain.

124 duces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels.

125 Notably, Galpha13 gain-of-function inhibits Akt activation and osteoclasto

126 behave in a dominant-negative manner due to gain-of-function interactions with the PP2A inhibitor TI

127 brain function, as both loss-of-function and gain-of-function KCNQ2 variants can lead to various form

128 Specifically, both loss-of-function and gain-of-function KCNQ5 mutations, associated with increa

129 Dyrk1a loss of function and gain of function led to defects in dendritic growth, den

130 entral (loss-of-function) and double-dorsal (gain-of-function) limb phenotypes, no direct gene target

131 tiation to endothelial lineage via loss- and gain-of-function (LOF and GOF).

132 Our findings support a primary toxic gain of function mechanism and highlight a previously un

133 dynamics and acted through a dominant toxic gain of function mechanism.

134 lated liver disease is therefore caused by a gain-of-function mechanism due to accumulation of the mu

135 r if a loss-of-function mechanism or a toxic gain-of-function mechanism is responsible for ARS-mediat

136 One proposed gain-of-function mechanism is that repeat-containing RNA

137 iency is lethal, supporting a hypomorphic or gain-of-function mechanism of action for Actr2(p.R258G)

138 t VCP disease mutants cause IBMPFD through a gain-of-function mechanism, and that VCP inhibitors have

139 ers, suggesting that these effects reflect a gain-of-function mechanism; whereas overexpression of ne

140 Both loss-of-function and gain-of-function mechanisms have been proposed to underl

141 ere reversed, suggesting that both loss- and gain-of-function mechanisms play a role in disease patho

142 luding male and female animals) in which the gain-of-function MEK1DD allele produces sustained MAPK/E

143 Osteoblast-specific miR-23a cluster gain-of-function mice have low bone mass associated with

144 In humans, postulated gain-of-function missense mutations cause Baraitser-Wint

145 Gain-of-function missense mutations in NLRP3 cause the d

146 Gain-of-function missense mutations in NLRP3 result in a

147 associated with distinct disease phenotypes: gain-of-function missense mutations, linked in two diffe

148 In contrast, heterozygous gain-of-function missense mutations, mainly localized at

149 Loss- and gain-of-function models have shown that neurons are sens

150 Using a conditional gain-of-function mouse model, we recently demonstrated t

151 sion in adult ovaries, we generated an Rspo1 gain-of-function mouse model.

152 ecific and osteocyte-specific WNT1 loss- and gain-of-function mouse models.

153 chromosomes for loss-of-function as well as gain-of-function mutagenesis for functional gene annotat

154 While ET receptor gain-of-function mutant ein4-1 attracted more SCN than t

155 In barley, secondary mutations in the DELLA gain-of-function mutant Sln1d (4) also uncoupled meriste

156 erformed a forward genetic screen to isolate gain-of-function mutants from an egress-deficient cdpk3

157 Loss- and gain-of-function mutants in A. thaliana were studied.

158 rg-28 suppressed phenotypic defects of slo-1 gain-of-function mutants in locomotion, neurotransmitter

159 Here, we used selective loss- or gain-of-function mutants of estrogen receptor alpha (ERa

160 opening and pathogen resistance in loss- and gain-of-function mutants.

161 on genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor re

162 torage disorder mucolipidosis type IV, and a gain-of-function mutation (Ala419Pro) in TRPML3 gives ri

163 partially recovered by BR treatment and the gain-of-function mutation bzr1-1D, which causes accumula

164 alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival.

165 derived cardiomyocytes from a patient with a gain-of-function mutation in Nav 1.5 (Long QT3 syndrome)

166 cervical cancer cell lines, they harbored a gain-of-function mutation in p53 (R273C).

167 A missense, gain-of-function mutation in the sodium leak channel NAL

168 This gain-of-function mutation increases glutamate and glycin

169 mEC neuron excitability associated with the gain-of-function mutation of Nav1.6 may increase excitat

170 It is shown that the gain-of-function mutation of TTP impairs IL-10-mediated

171 n to block fibrin accumulation or a Gi2alpha gain-of-function mutation to expand the thrombus shell.

172 ssociated with the SQT2-related V307L KCNQ1 'gain-of-function' mutation, which increases slow-delayed

173 Rare gain of function mutations in NaV1.7 lead to spontaneous

174 Individuals possessing gain of function mutations in the kinase domain such as

175 cancers, particularly those harbouring Notch gain of function mutations, including T-cell acute lymph

176 Changes in the basal activity by gain-of-function mutations also resulted in predictable

177 nsient receptor potential channel C6 (TRPC6) gain-of-function mutations and increased TRPC6 expressio

178 Most recently, the concept of gain-of-function mutations associated with PIDs has beco

179 Crucially, the gain-of-function mutations could be pharmacologically mo

180 Myocilin (MYOC) dominant gain-of-function mutations have been reported in approxi

181 lex disorder Cantu syndrome (CS) arises from gain-of-function mutations in either KCNJ8 or ABCC9, the

182 men aged 39-90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast gro

183 Gain-of-function mutations in histone 3 (H3) variants ar

184 This is key as gain-of-function mutations in human Nav1.7 recapitulate

185 Gain-of-function mutations in human PDGFRB have been lin

186 Gain-of-function mutations in iRHOM2 underlie Tylosis wi

187 Gain-of-function mutations in JAZ2 prevent stomatal reop

188 Gain-of-function mutations in KCNJ2-encoded Kir2.1 chann

189 Loss- and gain-of-function mutations in methyl-CpG-binding protein

190 Gain-of-function mutations in Nav1.9 have been identifie

191 ectrum of heritable pain disorders linked to gain-of-function mutations in Nav1.9, strengthening huma

192 anomalies with overgrowth harbor postzygotic gain-of-function mutations in oncogenes.

193 atic ductal adenocarcinoma in the setting of gain-of-function mutations in p53.

194 focusing on emerging paradigms that involve gain-of-function mutations in Rac and guanine nucleotide

195 Gain-of-function mutations in some genes underlie neurod

196 ly, diffuse large B cell lymphoma-associated gain-of-function mutations in the caspase recruitment do

197 is unknown whether these mutations phenocopy gain-of-function mutations in the CTNNB1 gene encoding b

198 intramolecular ID binding, surprisingly, no gain-of-function mutations in the ID itself have been re

199 estinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine

200 Our results demonstrate that gain-of-function mutations in the tumor suppressor SAMD9

201 (EIEE13), is caused predominantly by de novo gain-of-function mutations in the voltage-gated Na chann

202 Gain-of-function mutations in the voltage-gated sodium c

203 al nerve disorder caused by dominant, toxic, gain-of-function mutations in the widely expressed, hous

204 The persistence and recurrence of noncoding gain-of-function mutations in these cases suggests that

205 Gain-of-function mutations in transmembrane protein 173

206 Gain-of-function mutations of classic transient receptor

207 Gain-of-function mutations of NLRP3 result in abnormal a

208 Several studies have identified gain-of-function mutations of TRPC6 and report induced e

209 d erythromelalgia (IEM), a disorder in which gain-of-function mutations render dorsal root ganglia (D

210 Gain-of-function mutations shortened the action potentia

211 Two KCNQ1 gain-of-function mutations that cause a genetic form of

212 Histone Lys-to-Met (K-to-M) mutations act as gain-of-function mutations to inhibit a wide range of hi

213 JAK1 and STAT3 gain-of-function mutations were found in some, but not a

214 ctive advantage for more strongly activating gain-of-function mutations within the same gene.

215 ations are distinct from those driven by WNT gain-of-function mutations, with implications for identi

216 , and p.Val162del lack-of-function or p.A69T gain-of-function mutations.

217 epilepsy therapy in individuals with GRIN2D gain-of-function mutations.

218 RPC6 mutations, the majority of which caused gain-of-function mutations.

219 ole brain in about half of the patients with gain-of-function mutations; and (iii) most severe early-

220 Long QT Syndrome 3 (LQTS3) arises from gain-of-function Nav1.5 mutations, prolonging action pot

221 To address this hypothesis, gain-of-function Nlrp3(A350V) knock-in mice were bred on

222 d behavioral analyses to determine whether a gain-of-function nonsynonymous OXTR SNP interacted with

223 yltransferase (GmSHMT08); however, the novel gain of function of GmSHMT08 in SCN resistance remains t

224 Gain of function of LncND in developing mouse cortex led

225 From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinc

226 the lack of specificity in targeting loss or gain of function of NK cells.

227 Gain of function of the complex leads to neurodegenerati

228 Gain of function of the exocyst, a conserved protein com

229 These mutations result in gain of function of the growth repressor product SAMD9.

230 ion by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss o

231 evolutionary process that partly led to the gain of function of this N-terminal coiled-coil domain i

232 Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s).

233 egenerative diseases are driven by the toxic gain-of-function of specific proteins within the brain.

234 Here, we show in utero gain-of-function of the psychiatric risk gene transcript

235 er a dominant-negative loss-of-function or a gain-of-function of the voltage-gated K+ channel Kv1.2,

236 y raise the larger question of whether other gain-of-function oncogenic transcription factors might a

237 However, certain transposition-induced gain-of-function or regulatory mutations may be of selec

238 s a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signalin

239 that expresses a truncated MAP7 and found a gain-of-function phenotype both in vitro and in vivo Fur

240 We term this gain-of-function phenotype observed with rs3814159 G "CD

241 associated PIEZO1 variants exhibit a partial gain-of-function phenotype with generation of mechanical

242 d Ser(213) mutated to glutamic acid showed a gain-of-function phenotype with significantly increased

243 by genetic sequencing implicate an abnormal gain-of-function phenotype, evidenced by thrombocytopeni

244 Most of these TRPC6 mutations cause a gain-of-function phenotype, leading to calcium-triggered

245 the developing mouse brain mimicked a Notch gain-of-function phenotype, suggesting that Myt1l allows

246 the most active variants eventually trigger gain-of-function phenotypes.

247 ht to determine whether the association of a gain-of-function polymorphism in plasminogen activator i

248 xpansion which has been assumed to result in gain of function, predominantly, for the ATXN2 protein.

249 TES148C) with improved reaction kinetics and gain-of-function processing of an unnatural, epimerized

250 C) and module (PikAIII-TES148C) that display gain-of-function processing of substrates with inverted

251 It was shown that IMiDs impart gain-of-function properties to the CUL4-RBX1-DDB1-CRBN (

252 ntrol astrocytes, suggesting potential toxic gain-of-function properties.

253 ated mRNA isoform that encodes an oncogenic, gain-of-function protein.

254 o defective lymphatic sprouting, while Dtx3l gain of function rescued impaired sprouting in Orai1 KO

255 , specializing in fields directly related to gain-of-function research (immunology, virology) predict

256 t peer associations overall, those opposing "gain-of-function" research are more sensitive to peers t

257 All mutations are gain of function, resulting in increased phosphorylation

258 Conversely, Dscam gain of function results in exuberant growth into the do

259 al phenotype of a mouse model expressing the gain-of-function SCN8A patient mutation, p.Asn1768Asp (N

260 e of interest, we carried out both loss- and gain-of-function screens to identify regulatory elements

261 focal (loss-of-function) versus generalized (gain-of-function) seizures and corresponding epileptic d

262 Mice carrying the Noonan syndrome-associated gain-of-function SHP2 mutation (SHP2(D61G/+)) were resis

263 es, I propose that one or more low abundant, gain-of-function somatic mutations of the same 5 gene fa

264 of STAT1 and identify a novel mechanism for gain-of-function STAT1 disease in human subjects.

265 n this TMD region cancelled the effects of a gain-of-function Stg carrying mutation in its extracellu

266 al decaging to activate proteins or drugs in gain-of-function strategies.

267 ion, we performed Notch loss-of-function and gain-of-function studies in developing nephrons in mice.

268 In gain-of-function studies using mice overexpressing the h

269 However, gain-of-function studies using RSPO ligands and a new no

270 Gain-of-function substitution U103, in conjunction with

271 s of protein function and potentially toxic 'gain of function', such as the dominant P23H rhodopsin m

272 However, in vivo implementation of this gain-of-function system has proven difficult.

273 that the P158PfsX22 frameshift introduces a gain of function that gives rise to a dominant negative

274 he UNC13A variant causes a distinct dominant gain of function that is characterized by increased fusi

275 on neurite formation through a selective APP gain-of-function that could impact on axodendritic conne

276 idues uncoupled during activation and caused gain of function, the mutant pore residue favoured low c

277 Our results provide insights into how a gain of function through genetic recombination, in parti

278 ms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73.

279 n affected individual, the variant conferred gain of function to UBF, manifesting by markedly increas

280 ional and neoantigenic burden, more frequent gain-of-function TP53 mutations and a recurrent 11q13.5

281 YEATS mutations induced a gain of function, transforming primary hematopoietic cel

282 by enabling delivery of loss-of-function and gain-of-function transgenes with precise spatial-tempora

283 -beta rescues the phenotypes observed in the gain-of-function transgenic mice.

284 Conversely, in stable gain-of-function transgenics, Neurog2 promoted different

285 In contrast to gain of function variants that contribute to seizure, we

286 5 x 10(-11)) and genes with only missense or gain-of-function variants are more likely MAE (P<1.4 x 1

287 Pathogenic gain-of-function variants in the genes encoding phosphoi

288 approach, we isolated constitutively active gain-of-function variants of the AHK2 and AHK3 genes, na

289 PAI-1 gain-of-function variants promote airway fibrosis and ar

290 The gain-of-function variants, genotypes (AA/AG), were assoc

291 ich corresponded to the loss-of-function and gain-of-function variants.

292 which neurodegeneration is mediated through gain-of-function versus loss-of-function.

293 for the lack of thrombosis in patients with gain-of-function VWD.

294 S100A4 gain of function was sufficient to confer fibrotic prope

295 In six patients, the gain-of-function was diminished by an additional loss-of

296 By using loss and gain of function, we find that Sox2 expression requires

297 mechanisms are proposed to cause FXTAS: RNA gain-of-function, where CGG RNA sequesters specific prot

298 ApoE4 exerts a 'toxic' gain of function whereas the absence of ApoE is protecti

299 reveal when a particular substitution causes gain-of-function, which addresses a key challenge in int

300 s underlying mutp53 protein accumulation and gain-of-function will accelerate the development of targ