ライフサイエンスコーパス: loss-of-function

1 ction) significantly worse than deleterious (loss-of-function).

2 compare mutation-induced changes to genuine loss of function.

3 enes for which humans show poor tolerance to loss of function.

4 e splice variant of ATAD2B that results in a loss of function.

5 , more characteristic of patients with KCNA2 loss of function.

6 s in mammals do not regenerate and heal with loss of function.

7 om 1.8-fold that of WT SC(1-246) to complete loss of function.

8 debilitating, resulting in sensory and motor loss-of-function.

9 location, consistent with locus-independent loss-of-function.

10 function and for recessive variants, partial loss-of-function.

11 ed peak current) and 22 variants had partial loss of function (10%-50% normalized peak current).

12 tified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interac

13 dentification of 15 variants with consistent loss of function across different assays.

14 nvestigate the mechanism through which YIPF5 loss of function affects beta cells.

15 Several loss-of-function Aire mutants, including those causing a

16 Within the genotyped group, 53% of loss-of-function allele carriers were started on prasugr

17 e developed a mouse model where a congenital loss-of-function allele of Grin1 can be restored to wild

18 A loss-of-function allele of H2-Ob (Ob), originally mapped

19 Interestingly, a natural loss-of-function allele of ZmNLP5 in Mo17 conferred less

20 no UPF3B protein was produced, confirming a loss-of-function allele.

21 mma) energy radiation in mice carrying Trp53 loss of function alleles.

22 n to parasite pressure, multiple independent loss-of-function alleles at sorghum LOW GERMINATION STIM

23 ffective strategy to identify genes in which loss-of-function alleles produce mutant phenotypes.

24 Consistent with being loss-of-function alleles, we show using patients' primar

25 omeres, suggesting that the mutations create loss-of-function alleles.

26 icantly less rescue indicating that they are loss-of-function alleles.

27 only JAK/STAT activating mutations but also loss-of-function alterations of epigenetic modifiers.

28 Computational and genetic loss-of-function analyses corroborate the notion that ho

29 Loss-of-function analyses uncovered a transcriptional su

30 Gain- and loss-of-function analysis indicates that upregulation of

31 Here, using shared synteny to guide loss-of-function analysis of homologues of human enhance

32 Loss-of-function analysis showed that ADAR1 suppression

33 monstrate that GDF2 mutations result in BMP9 loss of function and are likely causal.

34 teins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6,

35 When examining the connection between pax2a loss of function and hyaloid vasculature, we observed si

36 n damage the polymer's integrity, leading to loss of function and properties.

37 rotein interaction landscape contributing to loss of function and, thereby, to hepatic copper toxicos

38 Using genome-wide loss-of-function and gain-of-function genetic technologi

39 kably, analysis of the frost recovery of ntt loss-of-function and mex1 overexpressor mutants confirme

40 Through loss-of-function and reconstitution experiments in pups,

41 in the human population that are potentially loss of function, and residues that modulate basal activ

42 olecular mechanisms using inducible gain and loss of function approaches in ILC2s and their precursor

43 and mouse atherosclerotic lesions, and used loss-of-function approaches in vitro in macrophages and

44 Gain- and loss-of-function approaches targeting these microRNAs im

45 Using gain- and loss-of-function approaches, we tested the role of p120-

46 IFITM1, IFITM2, and IFITM3, using gain- and loss-of-function approaches.

47 screens in mammalian cells commonly focus on loss-of-function approaches.

48 Gain and loss of function as well as genomic binding assays revea

49 re, combining chemical and genetic gain- and loss-of-function assays, we show that in rat hippocampal

50 In conclusion, human loss of function BDNF/TrkB variants that impair hippocam

51 eizure, indicating an epileptogenic role for loss-of-function Cacna1h gene variants reported in human

52 ing adenoviruses expressing CaM-wild type, a loss-of-function CaM mutation, CaM (1-4), and a gain-of-

53 We identified predicted heterozygous loss-of-function CASR variants (6 different nonsense/fra

54 Increase of ER stress in Tsc1 loss-of-function cells upon foxo knockdown was also conf

55 Loss-of-function CFK1 leads to increased DRM2 protein ab

56 Rice domestication tended to select de novo, loss-of-function, coding variation, while maize domestic

57 We found that Gli3 loss-of-function compromises the onset of Ascl-1(+) vome

58 afeguards neuronal RNA signatures in an ELAV loss-of-function context.

59 ovel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa

60 avivirus infection, we performed full-genome loss of function CRISPR-Cas9 screens.

61 Using a loss-of-function CRISPR screen in cells prestimulated wi

62 erall, we identified a significant excess of loss-of-function DNMs in genes highly expressed in crani

63 KMT2D NCC loss-of-function does exhibit unique phenotypes distinct

64 vation: that is, F302L causes both gain- and loss-of-function effects.

65 RSC remodeler, separate into two categories: loss-of-function enzymes, or instead, gain-of-function e

66 Moreover, Med19 loss of function experiments in vivo or in cellulo indic

67 Gain- and loss-of-function experiments indicated that linc-SPRY3-2

68 Gain-of-function and loss-of-function experiments with CYR61 in vivo point to

69 Partial loss-of-function Fech(m1Pas) mutant mice showed reduced

70 Although the proteomic analysis pointed to a loss of function for the D252H mutant protein, the D252H

71 and crosstalk in cancer, including selective loss of function for tumor-associated mutations.

72 calcium and reveal Tyr site-specific gain or loss of functions for calmodulin-induced eNOS activation

73 This signature can be used to distinguish loss-of-function from gain-of-function missense variants

74 n across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in f

75 ranscription factor Lef1 and using gain- and loss of function genetic mouse models, we demonstrate th

76 Through loss-of-function genetic analyses, we identified LOX3 an

77 ypic characterization identifies the crucial loss-of-function genetic events that occurred during the

78 By a loss-of-function genetic screening of individual IFN-sti

79 Loss-of-function genetic variants of triggering receptor

80 PCSK9 loss-of-function genetic variants were independently ass

81 with this predicted function, we found that loss-of-function GmKIX8-1 mutants showed a significant i

82 Therefore, it remains unknown how SYNGAP1 loss of function impacts the development and function of

83 Notably, PSEN1 loss of function impedes Endoplasmic Reticulum (ER)-to-l

84 Loss of function in ACO4, EIN2, EIN3 EIL1, ERF6, ERF016

85 However, Smad4 loss of function in all mature VSNs only compromises cor

86 Despite this proposed role of Pol IV, its loss of function in Arabidopsis does not cause a discern

87 Smad4 loss of function in immature bVSNs compromises dendritic

88 harboring recurrent cancer mutations exhibit loss of function in modulating the Hippo pathway, induci

89 herapeutic intervention that can reverse the loss of function in pSS.

90 ng with MDMX and inhibiting p53, and partial loss-of-function in suppressing Wnt signaling.

91 In this work, using gain-of-function and loss-of-function in vitro studies in patient-derived org

92 PCSK9 loss-of-function, in the context of low lipoproteins, ma

93 al modeling identified likely mechanisms for loss of function including altered thermostability and d

94 Akt2 loss-of-function increased anxiety-like phenotypes, impa

95 By contrast, we show that TMEM30A loss-of-function increases B-cell signaling following an

96 ducible genes RPL4A and RPL4D, and that RPL4 loss-of-function increases osmotic stress tolerance and

97 that ADHD-associated alleles are enriched in loss of function intolerant genes, supporting the role o

98 g genes in schizophrenia-enriched gene sets (loss-of-function intolerant and synaptic gene sets) were

99 CNVs hitting loss-of-function intolerant genes were associated with l

100 lates T4SS function during murine infection, loss of function is also associated with changes in othe

101 roprotein convertase subtilisin/kexin type 9 loss-of-function is associated with improved sepsis outc

102 Conversely, ATXN1 loss-of-function is implicated in cancer development and

103 es as a hypomorphic allele compared to a new loss-of-function (knock-out) mouse model.

104 While loss-of-function lines phenocopy the stunted root hair p

105 criptional and epigenetic responses to GATA6 loss of function (LoF) and missense variants during card

106 hemizygous for variants predicted to cause a loss of function (LoF) of the corresponding protein do n

107 se-causing genes are generally considered as loss-of-function (LoF) alleles and classified as pathoge

108 99Asp in the catalytic SET domain, behave as loss-of-function (LoF) alleles.

109 Here, we report novel heterozygous predicted loss-of-function (LoF) and predicted damaging missense v

110 and that is comparable-but complementary-to loss-of-function (LOF) constraint metrics(2).

111 odevelopmental movement disorder caused by a loss-of-function (LOF) mutation in the TOR1A gene encodi

112 f ccRCC patients treated with ICB (n = 189), loss-of-function (LOF) mutations in PBRM1 are not associ

113 we used genome-wide association to identify loss-of-function (LOF) mutations in the efflux pump mtrC

114 RNF43 loss-of-function (LOF) mutations that increase cell surf

115 Loss-of-function (LOF) variants in FLG associated with s

116 e identified twelve individuals with de novo loss-of-function (LoF) variants in protein phosphatase 1

117 ssible to derive estimates of intolerance to loss-of-function (LoF) variation for human genes.

118 ive pathogenesis through a dominant-negative loss-of-function mechanism in autophagy and that UBQLN2

119 The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are

120 Here, we highlight known loss-of-function mechanisms underlying ALS, potential co

121 While mice heterozygous for loss-of-function Megf8 or Mgrn1 mutations were normal, d

122 Male, but not female, Dusp8 loss-of-function mice, either with global or corticotrop

123 esticular reprogramming observed in XX Rspo1 loss-of-function mice.

124 y parallel screen in human cells to identify loss-of-function missense variants in the key DNA mismat

125 A zebrafish loss-of-function model using morpholinos was created to

126 Importantly, genetic rescue by the loss-of-function mutant indicates that barbed-end bindin

127 We generated a loss-of-function mutant of a coiled-coil domain containi

128 The loss-of-function mutant of BIN2 and its homologs, bin2-3

129 as in vivo physiological studies in an LCI1 loss-of-function mutant to reveal the C(i) species prefe

130 Using the EXORIBONUCLEASE4 (XRN4) loss-of-function mutant, we showed that XRN4 poly(A(+))

131 Although single loss of function mutants of ELF3 and GI have been well s

132 ogen insensitivity syndrome (AIS)-associated loss-of-function mutants and 168 prostate cancer-associa

133 n of Pm5e was validated by transgenic assay, loss-of-function mutants and haplotype association analy

134 bhlh121 loss-of-function mutants displayed severe defects in Fe

135 Loss-of-function mutants in both homeologs of AP2L2 (hen

136 dent in the embryonic epidermis of zebrafish loss-of-function mutants in the cognate Matriptase inhib

137 imilar to the rgi1/2/3/4/5 quintuple mutant, loss-of-function mutants of MPK3 and MPK6, MKK4 and MKK5

138 evelopmental processes in situ by generating loss-of-function mutants within otherwise wildtype tissu

139 and root apical meristems observed in fbl17 loss-of-function mutants.

140 Three-week-old mice heterozygous for a loss-of-function mutation in forkhead box I3 (FOXI3), a

141 Hypothesizing that loss-of-function mutation in the lipid-metabolism-relate

142 intellectual disability syndrome caused by a loss-of-function mutation in the spermine synthase (SMS)

143 ce, a murine model with a homozygous partial loss-of-function mutation in Vps54 (GARP protein) that c

144 re assessed by the probability of NPC1 being loss-of-function mutation intolerant and Z-scores of obs

145 a homozygous, maternal zygotic snx14 genetic loss-of-function mutation were both viable and anatomica

146 ements taken from human Dent1 disease (CLCN5 loss-of-function mutation).

147 tasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncha

148 an alteration in gene function rather than a loss-of-function mutation.

149 brafish that permits the rapid generation of loss of function mutations and the knock-in of specific

150 Loss of function mutations in COMT reduces syringyl (S)

151 Patients with loss of function mutations in DDR2 develop spondylo-meta

152 ortical processing phenotypes resulting from loss of function mutations in the Setd1a gene, a recentl

153 Loss of function mutations of the chorein-encoding gene

154 utations have been identified but no obvious loss of function mutations, though large heterozygous de

155 equences resulting from gain-of-function and loss-of-function mutations affecting insulin-like growth

156 predisposition in both carriers of germline loss-of-function mutations and genetically engineered mo

157 For FRI, loss-of-function mutations are positively selected and w

158 l ligand identification and the discovery of loss-of-function mutations associated with human disease

159 Here, I speculate that easier access to loss-of-function mutations has led them to play a major

160 Recessive loss-of-function mutations in ATP13A2 (PARK9) are associ

161 Loss-of-function mutations in both alleles of the human

162 Germline loss-of-function mutations in BRCA1 interacting protein

163 quencing of bladder cancer has revealed that loss-of-function mutations in chromatin regulators and m

164 ) is a debilitating genodermatosis caused by loss-of-function mutations in COL7A1 encoding type VII c

165 -catenin in the ventral hindgut via gain- or loss-of-function mutations in Ctnnb1 or Apc, respectivel

166 Loss-of-function mutations in DJ-1 were found to cause a

167 xtreme SCC susceptibility caused by germline loss-of-function mutations in FA DNA repair pathway gene

168 hat paralysis-resistant mutants all harbored loss-of-function mutations in genes required for cilioge

169 Bi-allelic loss-of-function mutations in genes required for the de

170 framework for understanding how heterozygous loss-of-function mutations in histone-modifying enzymes

171 Mendelian genetics attributes loss-of-function mutations in key mitophagy regulators P

172 Epigenetic modifiers frequently harbor loss-of-function mutations in lung cancer, but their tum

173 The identification of loss-of-function mutations in MKRN3 in patients with cen

174 Loss-of-function mutations in nine of the 12 genes limit

175 The syndrome is caused by loss-of-function mutations in NR2F1, which encodes a hig

176 Cultures harboring loss-of-function mutations in PKHD1 also recapitulate th

177 (n = 94) harbor chromosomal deletions and/or loss-of-function mutations in RB1 and TP53 (88% carry al

178 an example, we generated EHA105 strains with loss-of-function mutations in recA, which were fully fun

179 (2020) describe loss-of-function mutations in SERPINA12 as a cause of di

180 Homozygous loss-of-function mutations in SLC39A8 result in undetect

181 Loss-of-function mutations in SPRED1 occur in human canc

182 set of a myopathy associated with homozygous loss-of-function mutations in SVIL.

183 Finally, we showed that loss-of-function mutations in the ABCC4 gene, associated

184 riovenous malformations (AVMs), is caused by loss-of-function mutations in the ALK1/ENG/Smad1/5/8 pat

185 Loss-of-function mutations in the E3 ubiquitin ligase pa

186 (HI), a devastating skin disorder caused by loss-of-function mutations in the gene ABCA12, is poorly

187 Loss-of-function mutations in the LUBAC components HOIP

188 y-onset neurodegenerative syndrome caused by loss-of-function mutations in the multiple inositol-poly

189 Loss-of-function mutations in the NGLY1 gene cause NGLY1

190 erized by cholesterol accumulation caused by loss-of-function mutations in the Npc1 gene.

191 (2020) demonstrate that gain- and loss-of-function mutations in the peroxisomal acyl-CoA o

192 y heterozygous, autosomal-dominant, germline loss-of-function mutations in the SOCS1 gene in ten pati

193 Pseudomonas aeruginosa strains with loss-of-function mutations in the transcription factor L

194 phocyte development, PI3K-AKT/mTOR (6%), and loss-of-function mutations in TP53 (12%) were also ident

195 Human genetic studies have shown that the loss-of-function mutations in TREM2 signaling are strong

196 FLG loss-of-function mutations modify the relationship betwe

197 function cancer-associated mutations and all loss-of-function mutations physically localize to distin

198 engineered to express single or multiplexed loss-of-function mutations recurrent in chronic lymphocy

199 advances include recent work showing gain or loss-of-function mutations relating to driver or bystand

200 ecause homomeric GlyRs are more sensitive to loss-of-function mutations than heteromers.

201 e bearing human ALS-associated TBK1 missense loss-of-function mutations, or mice in which the Tbk1 ge

202 sing reporter assays, RNA-seq, ChIP-seq, and loss-of-function mutations, we can show that all of thes

203 gistry uncovered recurrent biallelic TMEM30A loss-of-function mutations, which were associated with a

204 observed for synonymous, non-synonymous and loss-of-function mutations.

205 FR amplifications and Sub1, Trp53, and Tead2 loss-of-function mutations.

206 Genetic gain-of-function and loss-of-function Na(V)1.7 mutations have been identified

207 Aging is characterized by a gradual loss of function occurring at the molecular, cellular, t

208 alterations in BLCA are associated with the loss of function of aldehyde oxidase (AOX1).

209 Previous studies demonstrated that loss of function of ANK or ENPP1 (reducing PP(i)) result

210 The loss of function of AtANN1 substantially impaired freezi

211 Partial loss of function of dynein light chain or Hook also enha

212 Studies of T cell trafficking found that the loss of function of endothelial R-Ras impairs the rapid

213 repair, although the underlying mechanism of loss of function of exosomes from inflamed EPCs is still

214 Loss of function of FRS7 and FRS12 results in plants wit

215 Distinct loss of function of IDO in smooth muscle cells, inflamma

216 Loss of function of SLB1 led to reduced leaf and flower

217 Loss of function of SMO4 results in a mild morphological

218 Partial loss of function of Spn-F, a downstream phosphorylation

219 yperdopaminergic state may be secondary to a loss of function of the adenosinergic system.

220 tant line, characterized the consequences of loss of function of these cytokines.

221 We propose that the combined loss-of-function of both redox metabolism-related system

222 e demonstrated in human and mouse cells that loss-of-function of FANCA or FANCC, products of 2 genes

223 The loss-of-function of HOS15 or HDA9 confers enhanced resis

224 se in thalamic inhibition is enhanced by the loss-of-function of the astrocytic GABA transporter GAT-

225 e of the variants are predicted to result in loss-of-function of the protein.

226 We report a patient with a loss-of-function of the secreted matricellular protein S

227 Loss-of-function of the transcription factor Gli3 is kno

228 We found that loss-of-function of two uclacyanins (UCC1 and UCC2) redu

229 A hallmark of ccRCC is genetic loss-of-function of VHL (von Hippel-Lindau) that leads t

230 d that FUS-ALS mutations induce a widespread loss of function on expression and splicing.

231 To study the consequences of TMPRSS9 loss of function on the mammalian brain, we generated a

232 eq and RNA-seq) to assess the effect of GCN5 loss-of-function on the expression and epigenetic regula

233 hown that mutations of TP53 not only lead to loss of function or dominant negative effects, but also

234 The loss-of function OsCYP20-2 mutant showed sensitivity to

235 the field should be cautious in interpreting loss-of-function phenotypes and must consider both cellu

236 terns of dysfunction, replicating the inborn loss-of-function phenotypes and, therefore demonstrate t

237 methods allows for precise determination of loss-of-function phenotypes free from secondary effects

238 selective inhibitors recapitulates the HDAC6 loss-of-function phenotypes.

239 sian ancestry, and there were many predicted loss-of-function (pLOF) and nonsynonymous variants that

240 Here, by manual curation of putative loss-of-function (pLoF) variants in haploinsufficient di

241 Loss-of-function polymorphisms in CYP2B6 result in highe

242 In support of this model, UTX loss-of-function potentiated FGFR3-dependent transcripti

243 in both sporadic and familial PD upon parkin loss-of-function remains unknown.

244 ggest that altered metabolism induced by SXR loss of function resulted in the accumulation of hydroxy

245 PCSK9 loss-of-function resulted in low lipoproteins and decrea

246 MRAP2 loss-of-function results in obesity in mammals.

247 teracting partner of AtPRMT3, and found that loss-of-function rps2a2b mutants were phenotypically rem

248 s perform a genome-wide CRISPR-Cas9-negative loss-of-function screen and identify WEE1 kinase as a th

249 , here we employed a genome-wide CRISPR/Cas9 loss-of-function screen in HeLa cells using selection fo

250 Here, we performed a genome-wide CRISPR loss-of-function screen to identify Foxp3 regulators in

251 COVID-19, we performed a genome-scale CRISPR loss-of-function screen to identify host factors require

252 n factors recently nominated by genome-scale loss-of-function screens from the cancer dependency map

253 Cell surface-based loss-of-function screens reveal that ATP7A, a copper-exp

254 Here, we conducted comprehensive gain- and loss-of-function screens using a human DUB cDNA library

255 -molecule drugs and genome-scale CRISPR-Cas9 loss-of-function screens.

256 sistance was determined in in vitro gain-and-loss of function studies and confirmed in subcutaneous a

257 Loss of function studies show that cardiomyocyte-specifi

258 Loss of function studies with in vivo models of H. pylor

259 Gain- and loss-of-function studies and fluorescent confocal micros

260 Moreover, loss-of-function studies indicated that the ZSWIM8 Culli

261 Gain- and loss-of-function studies of HDAC7 in cultured cardiomyoc

262 In loss-of-function studies, blocking antibodies revealed t

263 Using complementary gain- and loss-of-function studies, we observed that KLF6 overexpr

264 or Thr422 and Arg429 caused relatively large losses of function, suggesting functional roles for thes

265 egionally clustered, and a subset also cause loss of function through failure of myofilament incorpor

266 We attribute loss of function to defects in a chemical interaction ne

267 ucts, and the need to consider both gain and loss of function to develop safe and effective therapeut

268 ese genes and potential contribution of gene loss-of-function to ALS.

269 -exome sequencing data, we identified a GLI3 loss-of-function variant in a KS individual.

270 A common loss-of-function variant in HSD17B13 (rs72613567:TA) was

271 Bi-allelic loss of function variants in TMC6, TMC8, and CIB1 predis

272 an patient iPSC-derived microglia expressing loss of function variants in TREM2.

273 aggregating rare, predicted functional, and loss of function variants.

274 However, predicted loss-of-function variants are enriched for annotation er

275 All loss-of-function variants are located at the PALB2 coile

276 First, even essential genes, in which loss-of-function variants are not tolerated, can be high

277 tudy presents evidence that certain presumed loss-of-function variants in a cancer predisposition gen

278 This study aims to evaluate the impact of loss-of-function variants in AP-4 subunits on intracellu

279 e focused on the frequency and effect of FLG loss-of-function variants in association with self-repor

280 Although loss-of-function variants in DLL4 are known to cause Ada

281 udies and should guide the interpretation of loss-of-function variants in drug development.

282 ddition to autism, individuals with putative loss-of-function variants in DYRK1A exhibit microcephaly

283 Bi-allelic loss-of-function variants in genes that encode subunits

284 Biallelic loss-of-function variants in HAAO or KYNU, two genes of

285 Loss-of-function variants in intolerant genes were conce

286 Our results suggest that biallelic loss-of-function variants in SLC7A6OS are a novel geneti

287 h specifically associated high impact likely loss-of-function variants in the genetically constrained

288 Results - Heterozygous, high impact, likely loss-of-function variants in the Kinase Insert Domain Re

289 e identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering

290 Altogether, our data indicate that de novo loss-of-function variants in TOMM70 result in variable w

291 We also identified biallelic loss-of-function variants in VPS41, another HOPS-complex

292 , a mutation of bicra that mimics one of the loss-of-function variants leads to craniofacial defects

293 ation in available family members identified loss-of-function variants of the X-chromosomal TLR7.

294 patients with severe COVID-19, rare putative loss-of-function variants of X-chromosomal TLR7 were ide

295 40 putative gain-of-function and 33 putative loss-of-function variants.

296 Here, we report bi-allelic loss-of-function variations in SMO in seven individuals

297 through evolution while the consequences of loss of function varies between species.

298 tal of 18 individuals harboring heterozygous loss-of-function VPS16 variants, and one with a microdel

299 n understanding tumor pathology and how PTEN loss of function, whether by genetic or non-genetic mech

300 Further, in vivo CRISPR/Cas9-mediated REEP5 loss-of-function zebrafish mutants show sensitized cardi