ライフサイエンスコーパス: gain-of-function

1 mutp53 have acquired new oncogenic function (gain of function).

2 TMD+Linker (severe phenotypes; predominantly gain-of-function).

3 anism of disease, consistent with a dominant gain of function.

4 eads to a decrease in R loops, likely from a gain of function.

5 minant negative effects, but also promotes a gain of function.

6 perpolarized membrane potentials, indicating gain of function.

7 rmer are loss of function and the latter are gain of function.

8 n atrophy (DRPLA) via a proposed novel toxic gain of function.

9 suggest that the D252H mutation results in a gain of function.

10 clear indication for a common protein-based gain-of-function.

11 opposing consequences of K(ATP) loss- versus gain-of-function.

12 D: does APOE4 increase AD risk via a loss or gain of function?

13 conserved core domains within AAPN creates a gain-of-function AAP2 mutant that rescues assembly of th

14 fers from Cantu syndrome, which is caused by gain-of-function ABCC9 mutations, reflecting the opposin

15 e majority of the mutations confer PLCgamma1 gain-of-function activity through increased inositol pho

16 arization was shortened in the presence of a gain-of-function AHA1 allele.

17 ental overgrowth syndrome caused by a mosaic gain-of-function AKT1 variant.

18 netic data demonstrated that Cdk2(Y15S) is a gain-of-function allele causing elevated kinase activity

19 In humans, the gain-of-function allele PIEZO1 E756del is highly prevale

20 ostly express DOA*0102, which we found was a gain-of-function allele.

21 einitiating translation to potentially yield gain-of-function alleles rather than the expected null o

22 nearly evenly partitioned between loss- and gain-of-function alleles.

23 llowing candidates for primary causes of CA: gain-of-function alterations of CEP19, CEP72, CTNNB1, PT

24 ncRNA promoter analyses, global cistrome and gain-of-function analyses confirm that increased MAFG si

25 Using both loss or gain of function and genomic approaches, we further diss

26 hat both overactivation and underactivation (gain of function and loss of function, respectively) of

27 IV-specific CD4(+) T cells and involves both gain of function and loss of function.

28 Toll-2 gain of function and neuronal activity at the critical p

29 utational scan scores identified 40 putative gain-of-function and 33 putative loss-of-function varian

30 endometrial and prostate cancers result from gain-of-function and dominant-negative effects toward BE

31 the respective proteins, resulting in toxic gain-of-function and eventually in neurodegeneration.

32 echanism for de novo variants could be toxic gain-of-function and for recessive variants, partial los

33 Genetic gain-of-function and loss-of-function experiments confir

34 Gain-of-function and loss-of-function experiments confir

35 Gain-of-function and loss-of-function experiments demons

36 Gain-of-function and loss-of-function experiments with C

37 In this work, using gain-of-function and loss-of-function in vitro studies i

38 Here, using gain-of-function and loss-of-function mouse models, we s

39 The craniofacial consequences resulting from gain-of-function and loss-of-function mutations affectin

40 Genetic gain-of-function and loss-of-function Na(V)1.7 mutations

41 likely associated with cholesterol flux, as gain-of-function and loss-of-function studies for choles

42 two genes within the EMGS, were subjected to gain-of-function and loss-of-function studies in several

43 Gain-of-function and mechanistic studies revealed that I

44 in the first two individuals, resulted in a gain of function, and conversely, the c.73A>G (p.Thr25Al

45 Moreover, using a gain-of-function approach, we discovered previously hidd

46 inhibition, short hairpin RNA knockdown, and gain of function approaches, we established that both SM

47 We used loss- and gain-of function approaches to study functions of XTH4 a

48 Zeb2 knockouts and separate acute loss- and gain-of-function approaches indicated that Zeb2 is essen

49 Genetic loss- and gain-of-function approaches show that Wnt5a functions as

50 We used loss/gain-of-function approaches to understand the role of TF

51 Here we identified a recurrent gain-of-function ARAF mutation (c.640T>C:p.S214P) in a 1

52 also shows that the genes affected by Rbfox1 gain of function are surprisingly different from those i

53 erlapping enhancer and suggesting an SLC30A8 gain of function as the cause for the increased risk for

54 4-alphaM1/alphaM3 interface generally led to gains of function, as previously reported for the prokar

55 apse in vivo Here, we developed an in vitro, gain-of-function assay for Kirrel3 using neuron cultures

56 Results from loss- and gain-of-function assays indicated that GBP2 is important

57 reticulin modulation may eliminate the toxic gain of function associated with aggregation of ZAAT in

58 epressed from secreting autoantibody, Pik3cd gain-of-function B cells are activated by self-antigen t

59 ts, Asn(4)-Ala and Thr(5)-Ala, which yielded gain-of-function behavior comparable to what has been fo

60 ter of the respective LRR-RK leads to strong gain-of-function brassinosteroid, floral abscission, and

61 ed, suggesting that mutant p53 may exert its gain of function by altering iron metabolism.

62 Remarkably, all gain-of-function cancer-associated mutations and all los

63 In vivo, only gain-of-function cancer-associated mutations conferred p

64 ecrease in BAG3 protein level and not only a gain of function caused by the dominant missense mutatio

65 curring STK19 D89N substitution represents a gain-of-function change, allowing increased phosphorylat

66 RASGRP1 overexpression bestows gain-of-function colony formation properties to bone mar

67 say and increased v-SNARE binding to exocyst gain-of-function complexes.

68 alanine-expanded PABPN1 that lead to loss or gain of function could contribute to pathology in OPMD.

69 We design a whole genome gain-of-function CRISPR activation screen using human mi

70 disorder with a unique, platelet-dependent, gain-of-function defect in fibrinolysis, without systemi

71 ad to mutant proteins stable enough to exert gain-of-function defects in rods and cones.

72 to circumvent this limitation by harnessing gain-of-function, destabilizing mutations in MEK.

73 the difficulty in targeting Prph2-associated gain-of-function disease and suggests that elimination o

74 el in which LGMDD1 mutations in DNAJB6 are a gain-of-function disease that is, counterintuitively, me

75 Recent evidence has shown that FUS toxic gain of function due either to mutations or to increased

76 ons, F97C and S141R, cause mutation-specific gain of function effects on Ca(v) 1.2-encoded L-type Ca(

77 rough loss of function and dominant negative/gain of function effects.

78 irment in N-glycosylation of CaV2.1 promotes gain-of-function effects and may participate in cerebell

79 These gain-of-function effects are likely to increase neuronal

80 Finally, the gain-of-function effects associated with the p.VYEEDM116

81 have hypomorphic, dominant-negative, and/or gain-of-function effects on DNA methylation under differ

82 ories: loss-of-function enzymes, or instead, gain-of-function enzymes that greatly improve DNA transl

83 otic gene programming, whereas analysis of a gain-of-function ETV1 RNA sequencing dataset from neonat

84 Furthermore, we performed gain of function experiments by overexpressing MEK2 prot

85 line and pharmacologically mediated loss and gain of function experiments that the epiblast provides

86 Genetic loss- and gain-of-function experiments followed by time-lapse micr

87 Gain-of-function experiments revealed a potential role o

88 tial clusters termed "3D cliques." Loss- and gain-of-function experiments show that Notch preferentia

89 Gain-of-function experiments using primary cortical neur

90 Subsequently, loss- and gain-of-function experiments were performed.

91 Through loss- and gain-of-function experiments, we demonstrate that mk act

92 Reprogramming T cells to express a gain-of-function EZH2 mutant resulted in an enhanced abi

93 Expression of the gain-of-function F406A/T407A RPTPalpha variant in HEK293

94 onal genetic studies were carried out in the gain-of-function fatty acid oxygenation 2 (fou2) mutant

95 Accordingly, gain-of-function for C/EBP-alpha increased claudin-5 exp

96 ed K874* mutation (but not expression of the gain-of-function G019S mutation or dominant negative mut

97 Through loss- and gain-of-function genetic approaches, we reveal that rest

98 Using genome-wide loss-of-function and gain-of-function genetic technologies, we are able to co

99 ing of strong GIs mined from a growth-based, gain-of-function GI map.

100 ation of surface-exposed moieties can confer gain-of-function glue properties to an inhibitor, and we

101 Gain of function (GOF) DNA binding domain (DBD) mutation

102 The variant is a gain of function (GOF) for induction of the late, but no

103 d gene in human cancers and mutant p53 has a gain of function (GOF) that promotes tumor progression a

104 Na(+) channel gain of function (GOF), arising in both inherited condit

105 Germline gain-of function (GOF) mutations in PIK3CD, encoding the

106 nse mutations, are enigmatic, and neomorphic gain-of-function (GOF) activities have been implicated.

107 ncreasing number of identified cancer-driven gain-of-function (GOF) mutants of p53, it is important t

108 bi but not Enza resistance, even if AR-FL is gain-of-function (GOF) mutated.

109 Patients with STAT1 gain-of-function (GOF) mutations also have susceptibilit

110 yndrome (CS) is a complex disorder caused by gain-of-function (GoF) mutations in ABCC9 and KCNJ8, whi

111 transcription (STAT) protein family, namely gain-of-function (GOF) mutations in STAT1 and STAT3 as w

112 We found that gain-of-function (GOF) p53 mutations downregulated the L

113 utant p53 (mtp53) and some contain oncogenic gain-of-function (GOF) p53.

114 mooth muscle-specific expression of a Kir6.1 gain-of-function (GoF) subunit resulted in severely impa

115 n glutamatergic neurons, we generated a FGFR gain-of-function (GOF) transgenic mouse, which expresses

116 Pathogenic loss-of-function or gain-of-function heterozygous variants in nuclear factor

117 n CICs with disparate p53 functional states: gain of function, high risk p53 mutation (p53HRmut) and

118 es of the viral N gene resulted in a partial gain of function in the chimeric trout-avirulent strain

119 hat ALS-linked FUS mutants can cause a toxic gain of function in the cytoplasm by repressing the tran

120 Loss or gain of function in the DWF or BZR1 genes altered the ti

121 Furthermore, optogenetic gain of function in thirst-modality-specific cell types

122 ns impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcript

123 CK1alpha mutations observed in tumors cause gain-of-function in cooperating with MDMX and inhibiting

124 ally with type I IFN-mediated disease due to gain-of-function in STING, a key adaptor of IFN signalin

125 of open angle glaucoma arises due to a toxic gain-of-function intracellular misfolding event involvin

126 We conducted a gain-of-function invasion screen, which identified two s

127 present molecular insights into a FUS toxic gain-of-function involving direct and aberrant RNA-bindi

128 reveal that a gain-of-function JAK1 genetic variant results in a mutan

129 n mouse model, the authors demonstrated that gain-of-function KATP mutations in vascular smooth muscl

130 Given this, we screened a gain-of-function library for human genes that increase t

131 of ALS/FTD and contributes to the FUS toxic gain of function linked to this disease spectrum.

132 lation, and cardiomyocyte-specific loss- and gain-of-function manipulations of glycolysis decrease an

133 lity of regular autoinhibition, suggesting a gain of function mechanism for the identified missense v

134 ions operate through haploinsufficiency or a gain of function mechanism, an important prerequisite fo

135 tutive channel activity and thus a different gain-of-function mechanism compared to the ZLS-associate

136 ebellar ataxia type 1 (SCA1) through a toxic gain-of-function mechanism in the cerebellum.

137 sults not only suggest that LLPS serves as a gain-of-function mechanism involved in the pathogenesis

138 n the SPASTC448Y mouse are consistent with a gain-of-function mechanism underlying HSP, with spastin

139 tified mutations are demonstrated to exert a gain-of-function mechanism, augmenting transforming grow

140 cally, this mutation involves both loss- and gain-of-function mechanisms affecting a broad array of c

141 producing pyrin B30.2 FMF variants show that gain of function MEFV mutations bypass inhibition by Yop

142 Gain-of-function methods based on gene overexpression ar

143 STING gain-of-function mice developed an interferon-independen

144 notypes are similar to those of beta-catenin gain-of-function mice.

145 her investigation was conducted using Piezo1 gain-of-function mice.

146 be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic

147 IL-33 are decreased in aged mice, and IL-33 gain of function mitigates age-related decreases in spin

148 Unlike beta-catenin gain-of-function models, which induce high Wnt/beta-cate

149 Using loss- and gain-of-function mouse models, we show that SAA1, SAA2,

150 Finally, by using both loss-of-function and gain-of-function mouse models, we showed that OXGR1 is e

151 Specifically, gain of function mutant p53 promotes cancer cell motilit

152 Smooth muscle-specific expression of Kir6.1 gain-of-function mutant (GoF) subunits results in profou

153 p53 gain-of-function mutant 273H and PARP1 interact with rep

154 of variants incompatible with AAP2 creates a gain-of-function mutant compatible with AAP2.

155 bnormal chloroplast development, whereas the gain-of-function mutant, bin2-1, exhibits insensitivity

156 r of deletion alleles, as well as a putative gain-of-function mutant, of PEZO-1 caused a severe reduc

157 advantage of this insight, we then create a "gain-of-function" mutant HC/B by replacing two nonaromat

158 Interestingly, STING gain-of-function mutants from patients interacted strong

159 n mutants and 168 prostate cancer-associated gain-of-function mutants in AR were found.

160 a proliferating cell model to identify such gain-of-function mutants in the epidermal growth factor

161 Loss- and gain-of-function mutants of BBX31 indicate that it acts

162 nd that both loss-of-function mutation and a gain-of-function mutation (G2019S) cause axon guidance d

163 mmune dysregulation resulting from a mosaic, gain-of-function mutation (S703I) in JAK1, encoding a ki

164 A gain-of-function mutation implicated a membrane and ESCR

165 The identification of a gain-of-function mutation in CACNA1C as the cause of Tim

166 Del2.5 is the first reported gain-of-function mutation in LDLR causing a large reduct

167 To date, a gain-of-function mutation in LDLR with a large effect on

168 mutation in which expression of this severe gain-of-function mutation is dependent upon Cre recombin

169 These findings indicate that a STAT1 gain-of-function mutation limits production of antiviral

170 The gain-of-function mutation N629D at the outer mouth of th

171 nsight into the pathogenic mechanism of this gain-of-function mutation of SCN8A and identify excitato

172 In contrast, a PM H(+)-ATPase gain-of-function mutation that results in a constitutive

173 We have identified a gain-of-function mutation, bamA (E470K) , that bypasses

174 s-of-function CaM mutation, CaM (1-4), and a gain-of-function mutation, CaM-M37Q, into the anterior w

175 l dysplasia and immunodeficiency a germline, gain-of-function mutation, K171R, in IKBKB.

176 We show that it is a gain-of-function mutation, with a hyperpolarizing shift

177 NG and TA are caused by a somatic activating gain-of-function mutation.

178 sh, we demonstrate that endothelial-specific gain of function mutations in Kras (G12D or G12V) are su

179 Gain of function mutations in MEFV responsible for the a

180 Known, gain of function mutations of TREK-1 (G137I, Y284A) reco

181 hC, and a hypothetical membrane protein) and gain-of-function mutations (aroE Thr182Ile, yhcF Thr74Il

182 CASR loss- or gain-of-function mutations cause familial hypocalciuric

183 lar degeneration and leukodystrophy, whereas gain-of-function mutations cause hyperaldosteronism.

184 C6 activity from enhanced gene expression or gain-of-function mutations contribute to cardiac and/or

185 studies reveal mechanisms through which CaV2 gain-of-function mutations disrupt excitation-inhibition

186 TRPV3 gain-of-function mutations have been identified in patie

187 Some of these tumors combine gain-of-function mutations in ACVR1, PIK3CA, and histone

188 sient expression techniques create loss- and gain-of-function mutations in black-grass with genotype

189 Most known oncogenes were identified by gain-of-function mutations in cancer, yet little is know

190 tations in complement-regulating proteins or gain-of-function mutations in complement-activating prot

191 nleukopenia, is caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (

192 ts with Cantu syndrome, a disorder caused by gain-of-function mutations in genes encoding Kir6.1 or S

193 ts with Cantu syndrome, a disorder caused by gain-of-function mutations in genes encoding Kir6.1/SUR2

194 Autosomal dominant gain-of-function mutations in human stimulator of interf

195 Gain-of-function mutations in KCNT1, the gene encoding S

196 We identified gain-of-function mutations in KRAS or BRAF genes in path

197 Here, we demonstrate gain-of-function mutations in KRAS or BRAF genes within

198 aused by homozygous or compound heterozygous gain-of-function mutations in MEFV, which encodes pyrin,

199 L, are characterized by heterozygous somatic gain-of-function mutations in nonsyndromic children, whe

200 Additionally, gain-of-function mutations in NOTCH2 are associated with

201 illustrated by the fact that both loss- and gain-of-function mutations in PI3K can cause immunodefic

202 ith monogenic immune dysregulation caused by gain-of-function mutations in PIK3CD, encoding the p110d

203 It is well accepted that gain-of-function mutations in SCN8A underlie the disorde

204 is a rare primary immunodeficiency caused by gain-of-function mutations in the CXCR4 gene.

205 tivate this sigma(I) stress response acquire gain-of-function mutations in the essential histidine ki

206 Importantly, the assay is stimulated by gain-of-function mutations in the Exo70 component of the

207 Using bioinformatics, we identified Glt(Ph) gain-of-function mutations in the flexible helical hairp

208 rome (MAS) is a mosaic disorder arising from gain-of-function mutations in the GNAS gene, which encod

209 ch aberrant mast cells accumulate because of gain-of-function mutations in the KIT receptor.

210 Recently, gain-of-function mutations in the mechanosensitive ion c

211 group of autoinflammatory diseases linked to gain-of-function mutations in the NOD-like receptor fami

212 of Noonan syndrome (NS) are associated with gain-of-function mutations in the phosphatase SHP2 (enco

213 Loss-of-function and gain-of-function mutations in the PI3Kdelta isoform have

214 d immunodeficiency caused by either dominant gain-of-function mutations in the PIK3CD gene encoding t

215 Gain-of-function mutations in the tyrosine kinase recept

216 mune pathways in their skin, and humans with gain-of-function mutations in their type 2 response deve

217 Here we studied the effects of hotspot gain-of-function mutations in Trp53 (the gene that encod

218 Gain-of-function mutations in with no lysine (K) 1 (WNK1

219 Somatic gain-of-function mutations of GNAQ and GNA11, which enco

220 eptic encephalopathy (DEE) caused by de novo gain-of-function mutations of sodium channel Na(v) 1.6 t

221 , thus illustrating the possible role of the gain-of-function mutations of the glycine receptor in de

222 Loss- and gain-of-function mutations of the putative active site r

223 Gain-of-function mutations of voltage-gated sodium chann

224 ages from PD patients where pathogenic LRRK2 gain-of-function mutations result in the accumulation of

225 hat these alleles represent a novel class of gain-of-function mutations that activate signaling indep

226 eliminate the function of genes rather than gain-of-function mutations that increase or qualitativel

227 of-function mutations are dominant over most gain-of-function mutations within the same as well as of

228 JAK-STAT3 gain-of-function mutations within this pathway and other

229 ritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations.

230 wild-type CEACAM5, indicating that they are gain-of-function mutations.

231 matic cycle is detuned by disease-associated gain-of-function mutations.

232 nd function were preserved in aged mice with gain-of-function nAChRs that provide enhanced olivocochl

233 nergic nicotinic receptors gating kinetics ("gain of function" nAChRs).

234 ontrol fibroblasts, reflecting the dominant, gain-of-function nature of the variant.

235 Gain-of-function NOTCH2 mutations can cause Hajdu-Cheney

236 Gain of function of 46 kDa Pax6 in late-passaged LNC res

237 In vivo, gain of function of Atg1, or its activator Acinus, cause

238 Indeed, gain of function of Ryk intracellular domain signaling r

239 ltered on the cancer cells through loss- and gain-of-function of CIITA, a master regulator of the MHC

240 ys variant of PLCD1 from germline leading to gain-of-function of PLCdelta1 as a causative genetic def

241 Gain-of-function of PRMT1V2 clearly activated the glucon

242 The underlying mechanism is a gain-of-function of the RAS-mitogen-activated protein ki

243 y using a synthetic agonist, we demonstrated gain-of-function of the trafficking defect, suggesting t

244 Haploinsufficiency versus gain-of-function or dominant-negative effects specific t

245 ein convertase subtilisin-like/kexin type-9) gain-of-function Ossabaw mini-pigs were studied in vivo

246 Our work thus demonstrates primarily gain-of-function outcomes through transcriptomic modific

247 Gain-of-function PCSK9 mutations associated with familia

248 Our findings represent the first neurexin gain-of-function phenotype and provide new fundamentally

249 edly produced the first neurexin presynaptic gain-of-function phenotype and revealed unanticipated no

250 HEK293 cells, RRVs exhibit a dominant toxic gain-of-function phenotype that worsens with increasing

251 These gain-of-function phenotypes are reverted by reexpression

252 majority of missense patient mutations cause gain-of-function phenotypes that cluster around the S6 g

253 ct by mutations like Y602C or R616Q produces gain-of-function phenotypes when TRPV4 is heterologously

254 ted sustained MTOR signaling due to a strong gain-of-function PI3KCA mutation.

255 Last, individuals with gain-of-function PIK3CD (PI3Kdelta) mutations and increa

256 hyperphosphorylation was observed in CYCA3;4 gain-of-function plants.

257 t contain each one loss-of-function with one gain-of-function point mutation in a series of possible

258 human GPRC6A-(KGKY) variant appears to be a gain-of-function polymorphism that positively regulates

259 850Q, in the human SCN8A channel and present gain-of-function properties of the mutant channel.

260 r function of p53 and often confer oncogenic gain-of-function properties, are very common in cancer(1

261 Gain-of-function PTPN11 mutations drive oncogenesis in s

262 cribed in a breast cancer patient, both have gain-of-function Rad50 ATP hydrolysis activity that resu

263 el of the SCL deficiency and find that SIRT5 gain-of-function reduces global protein succinylation an

264 estication more frequently favored standing, gain-of-function, regulatory variation.

265 This gain-of-function role for the mutant cPLA(2)alpha was al

266 Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-i

267 The major hit from our gain-of-function screen is the apical polarity determina

268 We previously reported an in vivo gain-of-function screen that identified ~30 genes with a

269 Here, we perform a genome-wide gain-of-function screen using a poorly permissive hepato

270 ntrolled by TGF-beta followed by an unbiased gain-of-function screening in multiple hPSC lines to ide

271 or as a key upstream activator of Myoc whose gain of function significantly deterred cancer-induced m

272 All methods captured beneficial effects (gain-of-function) significantly worse than deleterious (

273 In gain-of-function studies, expansion of the lung lymphati

274 that all of these mutations cause a protein gain-of-function that alters co-factor binding and incre

275 nating CMT1B, without exacerbating the toxic gain-of-function that underlies the neuropathy.

276 Although all of these mutations are gain-of-function, the mutations affect different aspects

277 excess p27 proteolysis or from an oncogenic gain of function through PI3K-mediated C-terminal p27 ph

278 ulum (ER) stress and liver disease through a gain-of-function toxic mechanism.

279 t overriding FUS autoregulation will trigger gain-of-function toxicity via altered autophagy-lysosome

280 tion is rescued by loss of tdp-1, suggesting gain-of-function toxicity.

281 at the increased cytokinin signaling in ARR1 gain-of-function transgenic lines is associated with inc

282 nerated several cell type-specific loss- and gain-of-function transgenic mouse models to investigate

283 Here, we found that overexpression of gain-of-function TRPC6 channel variants is cytotoxic in

284 GPIbalpha-adhesive A1 domain of VWF in both gain-of-function (type 2B) and loss-of-function (type 2M

285 e investigated associations between a Piezo1 gain-of-function variant common in individuals of Africa

286 We examined the effect of a gain-of-function variant in CETP (rs1800777, p.Arg468Gln

287 Our study confirms that the Piezo1 e756del gain-of-function variant is a frequent polymorphism pres

288 nalysis of all 7 cohorts found that the CETP gain-of-function variant was significantly associated wi

289 tically linked the DOA*0102 common allele, a gain-of-function variant, with human hepatitis B viral p

290 protein that expresses dominant-negative and gain-of-function variants associated with distinct immun

291 Further, de novo gain-of-function variants in PDGFRB, a tyrosine kinase r

292 that confer a growth advantage, specifically gain-of-function variants in PIK3CA.

293 use a new syndrome distinctly different from gain-of-function variants in the same gene.

294 assium channel alpha-subunit, and pathogenic gain-of-function variants in this gene have been associa

295 t these risk-related polymorphisms are toxic gain-of-function variants that cause kidney dysfunction,

296 he peptidyl transferase center and isolating gain-of-function variants that enable the ribosome to ov

297 These data support gain-of-function variation in SOS1 as a contributing fac

298 , the structure demonstrates that a clinical gain-of-function VWF variant (Y2561) is more likely to h

299 at paradoxically, our data suggest that this gain of function would cause interneurons to more readil

300 s only present in higher eukaryotes, lead to gain-of-function X-linked protoporphyria (XLP).