ライフサイエンスコーパス: loss-of-function

1 esmoid tumors can cause severe morbidity and loss of function.

2 l of the protein is not affected, suggesting loss of function.

3 and differential sensitivity to diazepam and loss of function.

4 brain insulin signaling might occur via tau loss of function.

5 Characterization of loss-of-function abi5 mutants in pea uncovered a role fo

6 To date, the consequences of loss-of-function ACTB mutations have not been proven con

7 Recently, a novel partial loss-of-function AKT2 coding variant (p.Pro50Thr) was id

8 mined that this signal reflects effects of a loss-of-function Ala43Thr substitution in APOC3 (rs14721

9 ify and characterise a mouse line carrying a loss of function allele in Katnal1.

10 llele was found, for the first time, to be a loss of function allele.

11 lete knockout mice while mice with a partial loss-of-function allele mimic the isolated retinal degen

12 Unexpectedly, cactus loss-of-function alleles decrease Dorsal nuclear localiz

13 We then created loss-of-function alleles for 12 genes and uncovered anta

14 RN patients is even more severe than that of loss-of-function alleles in telomerase components, we hy

15 nt and in two other pedigrees carrying clear loss-of-function alleles showed the presence of BAP1-ass

16 Indeed, ATRX loss of function alters cellular histone H3.3 pools and

17 Loss of function analysis revealed that Aire was importa

18 Strikingly, the loss-of-function analysis in an in vivo mouse tuberculos

19 tilizing pharmacological inhibition, genetic loss of function and FRET studies, we show that ENb-TRAI

20 Dyrk1a loss of function and gain of function led to defects in

21 r have dominant negative activities or cause loss of function and haploinsufficiency.

22 n and protein truncation leading to complete loss of function and loss of expression of LAT in the af

23 organs, which leads to disfigurement, pain, loss of function and mobility, neurovascular compromise,

24 uman disorders associated with UBE3A gain or loss of function and suggests that dysfunctional UBE3A m

25 Loss-of-function and chromatin occupancy experiments pos

26 nstructs into T cell lines demonstrated both loss-of-function and dominant-interfering activity upon

27 critical for normal brain function, as both loss-of-function and gain-of-function KCNQ2 variants can

28 Specifically, both loss-of-function and gain-of-function KCNQ5 mutations, a

29 tes nephron segmentation, we performed Notch loss-of-function and gain-of-function studies in develop

30 erlapping clinical manifestations identified loss-of-function and missense variants in KIAA1109 allow

31 ie within the kinase domain result in hPINK1 loss-of-function and provides a platform for the explora

32 Despite striking double-ventral (loss-of-function) and double-dorsal (gain-of-function) l

33 Here, using genetically loss-of-function approaches in mice, we show that Ntn1 d

34 Gain- and loss-of-function approaches were applied to determine th

35 By using both gain-of-function and loss-of-function approaches, we demonstrate that HIPK2 c

36 e function of these pathways is derived from loss-of-function approaches.

37 Therefore, our findings implicate a cellular loss of function as the basis for impaired pain sensatio

38 the generation of engineered chromosomes for loss-of-function as well as gain-of-function mutagenesis

39 d the function of gga-miR-219b, and the gain/loss of function assay showed gga-miR-219b inhibited cel

40 AS1, were further validated using RNAi-based loss-of-function assays.

41 Here, we find that Kcnq2 ablation or loss-of-function at subthreshold membrane potentials lea

42 Total and partial loss-of-function aux1 mutants were assessed against wild

43 on-induced cleavage were abolished in a TEP1 loss-of-function background.

44 Loss-of-function bsl1 mutants fail to initiate a bristle

45 bility of plant water transport tissues to a loss of function by cavitation during water stress is a

46 -L1 inhibition and in a mouse model of STAT3 loss-of-function by crossing them with PD-1 knockout mic

47 Severe loss-of-function cases were incompatible with life, wher

48 HTRA2 and PINK1 loss of function causes parkinsonism in humans and anima

49 nd exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this d

50 acellular domain resulted in either gain- or loss-of-function changes, part of which was attributable

51 vation of TMEM16A by the CLCA1 VWA domain in loss-of-function chloride channelopathies such as cystic

52 proximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-spe

53 cose transport in isolated muscles with AMPK loss of function combined with either pharmacological in

54 e of neuronal and molecular networks to gene loss of function could reveal some pathophysiological me

55 A new study employs genome-wide loss-of-function CRISPR/Cas9 screening to identify three

56 a SHORT syndrome child with a novel partial loss-of-function defect in PKCepsilon.

57 Accordingly, loss-of-function dsk2 mutants accumulate BES1, have alte

58 by an additional loss-of-function (gain-and loss-of-function) due to a hyperpolarizing shift of volt

59 The mir-279/996 defect phenocopies Notch loss of function during the sheath-neuron cell fate deci

60 ge clamp system revealed mutations with only loss-of-function effects (mostly dominant-negative curre

61 The vast majority of these mutations show loss-of-function effects and impair protein translation.

62 Here we demonstrate loss-of-function effects of multiple rare coding SNVs fo

63 of the reported mutations lead to change- or loss-of-function effects, whereas others do not alter th

64 perimental studies such as genetic gain- and loss of function experiments.

65 hibition and beta-catenin overexpression) or loss-of-function experiments (dominant negative TCF4).

66 verall glutamatergic neurotransmission, such loss-of-function experiments fail to adequately distingu

67 Gain- and loss-of-function experiments reveal that miR-327 targets

68 Basal lineage-specific profiling and genetic loss-of-function experiments revealed a critical role fo

69 Gain- and loss-of-function experiments revealed that PECAM-depende

70 e the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which

71 which carry the circadian period lengthening loss-of-function Fbxl3(Afh) mutation and perform patch-c

72 ictors to derive gene-level probabilities of loss of function for every gene across all strains.

73 phenotype although we could not distinguish loss of function from loss of secretion in these assays.

74 -of-function was diminished by an additional loss-of-function (gain-and loss-of-function) due to a hy

75 ortant implications for the understanding of loss-of-function genetic diseases and the identification

76 ins as targets for pharmacological rescue in loss-of-function genetic diseases.

77 Although RNAi has revolutionized loss-of-function genetic experiments, it has been diffic

78 de RNA libraries, we conducted a genome-wide loss-of-function genetic screen in an isogenic pair of h

79 oaches provides complementary information in loss-of-function genetic screens.

80 Loss-of-function genetic variants are frequently associa

81 , we investigate protein features underlying loss-of-function genetic variation and develop a machine

82 tative measurements of protein dynamics with loss-of-function genetics, mosaic analysis, and temporal

83 Although NMD-induced loss-of-function has been shown to contribute to the gen

84 s, but the specific defects caused by TDP-43 loss of function have not been described in detail.

85 Here, we utilized a loss-of-function HR-reporter substrate to simultaneously

86 n the heterozygous state but whose biallelic loss-of-function human phenotype has not been reported.

87 h gain of functions (i.e., upregulation) and loss of functions (i.e., downregulation).

88 Gain- and loss-of-function IKur mutations produced multiple mechan

89 Loss of function in 2 of the 3 patient alleles was obser

90 We show that beta-catenin loss of function in cardiac fibroblasts after trans-aort

91 ts and signaling feedback sequelae of mTORC1 loss of function in epithelial tissue.

92 abilized the AMPAR-Stg complex, with overall loss of function in gating modulation.

93 Genetic loss of function in mice and adoptive transfer studies r

94 Loss of function in other genes in the dopamine and sero

95 Here, we conditionally induce beta-catenin loss of function in resident cardiac fibroblasts using T

96 and genetic or experimental proof of gain or loss of function in select cases has clarified the direc

97 In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in

98 All eleven mutations cause a reduction or loss of function in the affected kinase.

99 However, the role of VHL loss of function in the development of ccRCC via inflamm

100 n development, as well as the role of Dyrk1a loss of function in the pathophysiology of autism.

101 hemotherapy via targeting downregulation (or loss of functions) in cancer cells.

102 The murine tumours exhibit PTEN loss of function instigated by reduced PTEN mRNA, and in

103 rol motivated behaviours and that VLS D2-MSN loss-of-function is a possible cause of motivation defic

104 for mitochondrial fine tuning, whereas TRAP1 loss of function leads to reduced control of energy meta

105 xcitability in the brain, where pathological loss of function leads to such disorders as epilepsy, Al

106 of mammalian Slo2) in Caenorhabditis elegans Loss-of-function (lf) mutants of hrpu-2 were isolated in

107 Neutrophil loss-of-function limited these findings.

108 Analyses of Arabidopsis loss-of-function lines revealed that the elimination of

109 tment use among patients with 0, 1, or 2 FLG loss of function (LOF) alleles was compared as well as t

110 iched in known driver genes.Variants causing loss of function (LoF) of human genes have clinical impl

111 majority of EA2 disease-causing variants are loss-of-function (LoF) point changes leading to decrease

112 ngenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating

113 PCSK9 loss-of-function (LOF) variants allow for the examinatio

114 Based on the genotyping of 2 loss-of-function (LoF) variants c.5101C>T (p.GIn1701Ter

115 PTPR-gamma loss-of-function lowers glycemia and insulinemia by enha

116 Pharmacological blockade or genetic loss-of-function manipulations that prevent NMDAR functi

117 wide DNA methylation in partial and complete loss-of-function met1 mutants.

118 yperopia (nanophthalmos) is a consequence of loss-of-function MFRP mutations.

119 etion mutant of FOF2 (FOF2DeltaF), or double loss of function mutant of FOF2 and FOL1 (FOF2-LIKE 1) p

120 importance of Nisch, here we generated Nisch loss-of-function mutant mice and analyzed their metaboli

121 to photoperiod in a manner similar to a cdf loss-of-function mutant.

122 Zebrafish rad51 loss-of-function mutants developed key features of FA, i

123 -function ET receptor mutant, etr1-3, or the loss-of-function mutants etr1-7 and ers1-3 and the wild

124 te this issue, we produced a complete set of loss-of-function mutants for the three annotated Arabido

125 n content and vein density were increased in loss-of-function mutants of Arabidopsis MYC2, a suppress

126 NA (mtDNA) in Arabidopsis thaliana Gain- and loss-of-function mutants provided evidence for a role of

127 istant locomotory behavior, resembling slo-1 loss-of-function mutants, albeit to a lesser extent.

128 d trunk mesoderm, and closely resemble nodal loss-of-function mutants.

129 e may be of interest to restore transport in loss-of-function mutants.

130 nted the observation of strong phenotypes in loss-of-function mutants.

131 mutants in Caki2 cells (ccRCC cells with the loss of function mutation in PBRM1).

132 to evaluate the medical consequences of the loss of function mutation p.Ser267Phe in SLC10A1.

133 We performed studies in mice with a Zeb2 loss-of-function mutation (Zeb2(Delta)) and mice carryin

134 This strain carries a loss-of-function mutation in actr10, a member of the dyn

135 rent homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK domain containing 1 (

136 The first of these is related to loss-of-function mutation of the TGF-beta/BMP receptor c

137 A loss-of-function mutation, alpha2E336A, in the alpha2-in

138 iagnosis with biallelic somatic deletion and loss-of-function mutation, thereby lacking a functional

139 ected over time, as expected for a recessive loss-of-function mutation.

140 lly as a recessive trait, as expected from a loss-of-function mutation.

141 rs, CHARGE and Kabuki syndromes, result from loss of function mutations in chromodomain helicase DNA-

142 gulated growth and differentiation caused by loss of function mutations in either the TSC1 or TSC2 ge

143 ing GPI anchor protein pathway genes induced loss of function mutations in human and mouse cell lines

144 In this study, loss of function mutations in the oligopeptide importer

145 probands with or without identified de novo loss of function mutations or copy number variants in hi

146 mutations included five de novo heterozygous loss of function mutations/deletions in the PBX homeobox

147 iquitously expressed in mammalian cells, its loss-of-function mutations are the direct cause of type

148 APC biallelic loss-of-function mutations are the most prevalent geneti

149 lation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age a

150 ression of the mutated TBK1 allele is due to loss-of-function mutations creating a premature terminat

151 In the tissue model, loss-of-function mutations facilitated breakdown of exci

152 Loss-of-function mutations had heterogeneous effects on

153 Significantly, both RhoA GTPase gain- and loss-of-function mutations have been discovered in prima

154 Loss-of-function mutations in 3'-to-5' exoribonucleases

155 Loss-of-function mutations in ALPL result in hypophospha

156 These data indicate that loss-of-function mutations in ANKZF1 result in deregulat

157 l lines and antigens, we identified multiple loss-of-function mutations in APLNR, encoding the apelin

158 Because HHT is caused by loss-of-function mutations in bone morphogenetic protein

159 Loss-of-function mutations in CBL E3 ubiquitin ligases a

160 SHP2 loss-of-function mutations in chondroid cells are linked

161 munodeficiency caused by autosomal recessive loss-of-function mutations in DOCK8.

162 rare autosomal recessive disorder caused by loss-of-function mutations in dopamine transporter (DAT)

163 ts with pseudohypoaldosteronism-1 because of loss-of-function mutations in epithelial sodium channel

164 Loss-of-function mutations in genes encoding effector pr

165 e combined immunodeficiency can be caused by loss-of-function mutations in genes involved in the DNA

166 In contrast, loss-of-function mutations in GLI1 have remained elusive

167 Loss-of-function mutations in GRN cause frontotemporal d

168 Loss-of-function mutations in KCC2 are a known cause of

169 s that provide growth advantage to cells via loss-of-function mutations in microsatellites are called

170 fection by Salmonella Typhimurium because of loss-of-function mutations in Nramp1 (SLC11A1), a phagos

171 Loss-of-function mutations in ORGANELLE RNA RECOGNITION

172 Inherited loss-of-function mutations in SCN5A lead to defects in t

173 Loss-of-function mutations in SLC30A10, a cell-surface-l

174 aberrations, we identified three homozygous loss-of-function mutations in SMARCD2.

175 This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been asso

176 eroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate ly

177 Loss-of-function mutations in SPOP compromise ubiquitina

178 Loss-of-function mutations in TET2 occur frequently in p

179 We previously identified loss-of-function mutations in the angiopoietin (ANGPT) r

180 children, largely results from heterozygous loss-of-function mutations in the brain voltage-gated so

181 Loss-of-function mutations in the BRCA1 and BRCA2 genes

182 ization in both lineages was associated with loss-of-function mutations in the BZP4 transcription fac

183 Loss-of-function mutations in the common gamma (gammac)

184 erial calcification of infancy (GACI) due to loss-of-function mutations in the ENPP1 gene.

185 Loss-of-function mutations in the FLG gene cause ichthyo

186 We identified homozygous loss-of-function mutations in the gene encoding CD55 (de

187 Specifically, loss-of-function mutations in the gene encoding LegC4 re

188 individuals were found to possess biallelic loss-of-function mutations in the gene encoding the axon

189 nked, dominant genodermatosis resulting from loss-of-function mutations in the IKBKG gene encoding nu

190 imately 20% of KRAS-mutant LUAD tumors carry loss-of-function mutations in the KEAP1 gene encoding Ke

191 l syndrome, a rare genetic disease caused by loss-of-function mutations in the matrix Gla protein (MG

192 Loss-of-function mutations in the MCOLN1 gene, which enc

193 lin (PGRN) haploinsufficiency resulting from loss-of-function mutations in the PGRN gene causes front

194 rcent of patients have compound heterozygous loss-of-function mutations in the Shwachman-Bodian-Diamo

195 entially fatal hereditary disorder caused by loss-of-function mutations in the survival motor neuron

196 et motor disorder DYT6 dystonia is caused by loss-of-function mutations in the transcription factor T

197 Furthermore, loss-of-function mutations in this TMD region cancelled

198 These studies demonstrate that biallelic loss-of-function mutations in THPO cause BMF, which is u

199 s a debilitating movement disorder caused by loss-of-function mutations in torsinA.

200 istance, we observed somatic and insertional loss-of-function mutations in transformation-related pro

201 Loss-of-function mutations in TTC19 (tetra-tricopeptide

202 ide a model for human patients with germline loss-of-function mutations in Wnt pathway genes, includi

203 urbed genes in human melanoma cells to mimic loss-of-function mutations involved in resistance to the

204 2, DDX3X, KDM5C, KDM6A, and MAGEC3) harbored loss-of-function mutations more frequently in males (bas

205 Loss-of-function mutations of beta-cell KATP channels ca

206 OMOD1 is caused by loss-of-function mutations of glypican 6 (GPC6).

207 t-onset dystonia DYT25 is caused by dominant loss-of-function mutations of GNAL, a gene encoding the

208 Loss-of-function mutations of KIB1 and its homologs abol

209 Common examples of the former are loss-of-function mutations of the PBRM1 and BAP1 tumor s

210 ole for PI(3,4)P2 in the phenotype caused by loss-of-function mutations or deletions in PTEN.

211 These phenotypes are suppressed by loss-of-function mutations that arise spontaneously in l

212 ssors that are frequently deleted or acquire loss-of-function mutations, the majority of TP53 mutatio

213 Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in

214 nked CNM, is caused by myotubularin 1 (MTM1) loss-of-function mutations, while the main autosomal dom

215 EG abnormalities for patients with gain- and loss-of-function mutations.

216 response (DDR) and are characterized by rare loss-of-function mutations.

217 y to result in offspring carrying homozygous loss-of-function mutations.

218 orders, moving beyond the more commonly seen loss-of-function mutations.

219 grains, similar to those observed in three Q loss-of-function mutations.

220 fibrosis in mice with adiponectin gain- and loss-of-function mutations.

221 rominent sleep activation in most cases with loss-of-function mutations; (ii) more severe epilepsy, d

222 deletions of 7q (7q-), and secondary somatic loss-of-function (nonsense and frameshift) mutations in

223 ed the diabetes-induced glial activation and loss of function of amacrine cells (brain nitric oxide s

224 The R482W mutation results in a loss of function of differentiation-dependent lamin A bi

225 nctional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mo

226 FXS results from the loss of function of fragile X mental retardation protein

227 Loss of function of KIND1, a cytoskeletal protein involv

228 The loss of function of MKK4/MKK5 also results in the same p

229 Gain and loss of function of PAPC in chicken embryos disrupted so

230 Heterozygous loss of function of PTEN in human subjects has a signifi

231 eptible to Lolium isolates), followed by the loss of function of PWT3 This implies that the rwt3 whea

232 noleukodystrophy, mutations in ABCD1 lead to loss of function of the ALD protein.

233 fibrosis (CF) lung disease is caused by the loss of function of the cystic fibrosis transmembrane co

234 Pathogenic mutations cause a loss of function of the encoded protein Parkin.

235 Our present study shows that loss of function of the P2X7 receptor in mice induces re

236 Loss of function of the Rho-GAP oligophrenin-1 is associ

237 Complete loss of function of the ubiquitous splicing factor SFPQ

238 es a less pronounced phenotype, suggesting a loss of function of these mutants in promoting NMJ remod

239 ablation/dysfunction technique, we find that loss-of-function of D2-MSNs within ventrolateral striatu

240 Loss-of-function of Ena/VASP, alpha5beta1-integrins or t

241 Loss-of-function of FRS7 and FRS12 results in early flow

242 initiation and progression in the context of loss-of-function of Pten, but alters tumor histopatholog

243 We found that genetic loss of function or ablation of the P2x7 gene inhibits s

244 Loss of function or elimination of T-bet-expressing Treg

245 ne KCNA2, causing either a dominant-negative loss-of-function or a gain-of-function of the voltage-ga

246 ominant diseases that feature both gain- and loss-of-function pathologies or have a heterogeneous gen

247 Using loss-of-function pericyte-deficient mice, here we show t

248 -collagen binding is independent of gain- or loss-of-function phenotype and under shear stress, plate

249 hat [SWI(+) ] formation results in a partial loss-of-function phenotype of poor growth in nonglucose

250 The reciprocal chimera (Rx1CN/Gpa2L) shows a loss-of-function phenotype, but exchange of the first th

251 MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemic

252 paired cysteines that mediate both gain- and loss-of-function phenotypes.

253 Previously we showed that etr1-6 loss-of-function plants germinate better and etr2-3 loss

254 -function plants germinate better and etr2-3 loss-of-function plants germinate worse than wild-type u

255 nvestigate the association of rare predicted loss-of-function (pLoF) variants within age-related macu

256 Loss-of-function point mutations in a component of this

257 All madC mutant strains contain loss-of-function point mutations within a gene predicted

258 Putative loss-of-function polymorphisms within the START domain p

259 In a loss-of-function PTPome screen, our laboratory identifie

260 ll help guide the proper use and analysis of loss-of-function reagents for the determination of gene

261 of single and multiple gain-of-function and loss-of-function receptor mutants revealed that, of the

262 KDM5C loss of function resulted in increased levels of H3K4me3

263 PR-Cas9 technology to perform a genome-scale loss-of-function screen in an MLL-AF4-positive acute leu

264 Here, using loss-of-function screening based on RNA interference, we

265 cer cell proliferation, we used genome scale loss-of-function screening in a large number of genomica

266 e performed parallel genome-wide CRISPR/Cas9 loss-of-function screens in BL and lymphoblastoid cell l

267 1) as the receptor for SVV using genome-wide loss-of-function screens.

268 ns to perform genome editing and facilitates loss-of-function screens.

269 egregation analyses followed, to determine a loss of function sequence variation in the phospholipase

270 of our patients segregated with a homozygous loss-of-function sequence variant, causing the substitut

271 dence suggesting that LRRK2 G2019S and SYNJ1 loss of function share a similar pathogenic pathway in d

272 addition, analysis of feedback-resistant and loss-of-function single and double mutants revealed that

273 hey are mostly mutually exclusive with other loss-of-function (stop/frameshift) variants.

274 in C. elegans, and we also found that grk-2 loss-of-function strains have abnormally high levels of

275 Gain- and loss-of-function studies indicated that AK144841 mainly

276 Gain- and loss-of-function studies show that Bcl11b induces cells

277 Loss-of-function studies showed that autophagy in NP cel

278 By gain- and loss-of-function studies, we establish that SRC stimulat

279 he absence of embryonic phenotypes in murine loss-of-function studies.

280 majority of the SCZ case variants exhibiting loss of function toward MAPK activation in a manner corr

281 ential of LoF variants, ALoFT (annotation of Loss-of-Function Transcripts) and show its application t

282 te that Dicer1 can function as a traditional loss-of-function tumor suppressor gene, and they provide

283 symptoms seen in patients with a missense or loss-of-function variant in KCNB1 and how these symptoms

284 erating Characteristic curve of 0.85 for all loss-of-function variants and 0.75 for proteins in which

285 When applied to de novo putative loss-of-function variants in autism-affected families, A

286 art defects, consistent with the severity of loss-of-function variants in humans.

287 hat have homozygous or compound heterozygous loss-of-function variants in PD cases.

288 sense variants in the ion channel domain and loss-of-function variants in this domain and the C-termi

289 Loss-of-function variants of the IL23-receptor gene (IL2

290 s in >6500 cancer exomes shows that putative loss-of-function variants predicted to be deleterious by

291 Rare, deleterious, nonsynonymous, or loss-of-function variants were filtered to identify vari

292 c variants and provides examples of intronic loss-of-function variants with pathological relevance.

293 is accomplished by observing intolerance to loss-of-function variants.

294 nisms underlying loss of protein function in loss-of-function variants.

295 burden persists in other genes intolerant of loss-of-function variants; although this effect is notab

296 main differences were (i) predominant focal (loss-of-function) versus generalized (gain-of-function)

297 Using a human endothelial cell line, PLD2 loss of function was shown to lower intracellular free c

298 In mice with mTORC1 loss of function, we found that Rho kinase (ROCK) signal

299 Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropo

300 emonstrate that the R30W mutation results in loss of function while also exerting a dominant negative