ライフサイエンスコーパス: missense

1 There were 607 SNPs mapped to missense, 29 SNPs mapped to nonsense, and 19 SNPs mapped

2 zygosity mapping unveiled a novel pathogenic missense ADAMTS17 variant (c.3068 G > A, p.C1023Y).

3 as discounted based on recovery of a crwn4-2 missense allele that disrupts a predicted NLS and lowers

4 However, these human SMN missense allele transgenes can rescue a null Smn allele

5 e crwn4-2 mutation led to the discovery of a missense allele, impa-1(G146E), in one of the nine impor

6 nges in human carriers of the common SLC39A8 missense allele.

7 First, missense alleles cause dominant peripheral neuropathy.

8 e loss-of-function activity, suggesting rare missense alleles in BRIP1 confer risk for both breast an

9 higher than the frequency of all rare BRIP1 missense alleles reported in more than 60,000 individual

10 from 17 599 proteins, of which 2 377 103 are missense and 161 928 are nonsense mutations.

11 We assayed 119 missense and 45 truncating RNF43 mutations found in huma

12 Here, we identify biallelic missense and frameshift mutations in NARS1 in seven pati

13 Multiple novel missense and frameshift variants in MFRP and PRSS56 were

14 We confirm that missense and nonsense variants in the FKBP-like and tetr

15 els in patients with idiopathic PAH.Methods: Missense BMP9 mutant proteins were expressed in vitro an

16 ed 10 previously reported mutations, 1 novel missense (c.83T>A; p.Ile28Asn) and 2 novel truncating (c

17 Missense CASR variants were identified in two unrelated

18 We find that missense changes within or near the DNA-binding domain (

19 in NR2E3 were identified, including 4 novel missense changes.

20 Pathogenic missense coding mutations were identified by in silico t

21 Mendelian disease genes(5), that outperforms missense constraint metrics(3) and that is comparable-bu

22 utyric acid transporter, was associated with missense-damaging DNVs.

23 DHEA) to potent androgens and has a germline missense-encoding polymorphism.

24 Three adults and 1 child shared a novel missense homozygous variant in the TNNT1 gene (NM_003283

25 e only gene with novel de novo variants (all missense) in at least three patients.

26 s with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remod

27 In conclusion, dominant missense KAT5 variants cause histone acetylation deficie

28 We establish that missense KIF21B variants impede neuronal migration throu

29 that mice bearing human ALS-associated TBK1 missense loss-of-function mutations, or mice in which th

30 D+AIC patient who displays a rare homozygous missense M466V mutation in beta-catenin-like protein 1 (

31 4.2 channels was weaker for the JNCL-related missense mutant CLN3(R334C) and for a JNCL-related C-ter

32 owever, co-expression of two different huSMN missense mutants can rescue iMEF survival and small nucl

33 Temperature-sensitive (TS) missense mutants have been foundational for characteriza

34 of biochemical and biophysical changes in TS missense mutants within the context of their functional

35 syndrome (86%) are caused by a heterozygous missense mutation (c.148G>A, p.D50N) in the GJB2 gene, e

36 a codon deletion mutation (Delta1313) and a missense mutation (I1314L) in the L polymerase.

37 report that the human infertility-associated missense mutation (N64I) in MEIOB causes protein degrada

38 died of autoinflammation due to a homozygous missense mutation (R148Q) in STAT2.

39 isolates of emm subtype emm43.4 with a pbp2x missense mutation (T553K) were detected.

40 Strikingly, however, this missense mutation affects B cell development but not thy

41 d, resulting in homozygous expression of the missense mutation allele.

42 iable depending on the interplay between the missense mutation caused by the read-through and the str

43 Especially, as a missense mutation E102Q in S1R has been reported in few

44 the RSV polymerase gene and the stabilizing missense mutation I1314L.

45 A missense mutation in a highly conserved residue in the R

46 ion of a third case with a possibly damaging missense mutation in ATP1A3 and three others cases with

47 ngs with IMD identified a novel heterozygous missense mutation in BPIFA1/SPLUNC1.

48 t1/3 low seed-set phenotype, we identified a missense mutation in exo70a2, a predicted member of the

49 ingle strand DNA relative to H1047R (A3140G) missense mutation in exon 20 in breast cancer as the mod

50 A missense mutation in FOLH1 (rs202676 G allele) was assoc

51 We identified a heterozygous missense mutation in PYGM segregating with the disease i

52 We identified a novel de novo missense mutation in SEC61A1 (c.A275G;p.Q92R) in a patie

53 A homozygous missense mutation in the gene encoding the estrogen rece

54 st coding variant in schizophrenia GWAS is a missense mutation in the manganese transporter SLC39A8,

55 g a hypomorphic mutation in one allele and a missense mutation in the other are the most severely aff

56 d focused next-generation sequencing found a missense mutation in the Phosphatidylinositol-4,5-Bispho

57 modeled in Pstpip2(cmo) mice, which carry a missense mutation in the proline-serine-threonine phosph

58 We expect that a missense mutation in this critical overlap region associ

59 ne splicing analyses revealed that the AMELX missense mutation increased exonic definition of exon 4

60 Recently, a novel missense mutation Met48Lys in FKBP22 was identified in a

61 Our study characterized that a missense mutation on phenylalanine residue located in CR

62 We created a mouse model with a missense mutation p.Ser6366Ile and a deletion of NEB exo

63 nctionally characterizes the most common ATM missense mutation R3008H in cancer and identifies a uniq

64 The missense mutation resulted in a loss of function of HilD

65 The missense mutation severely limits the glycosylation of N

66 Mice that are heterozygous for the missense mutation show no behavioural abnormalities but

67 PIK3CA c.3140 A > G (H1047R), a prevalent BC missense mutation that is attributed to BC tumour growth

68 dentified a rare TP53 tetramerization domain missense mutation, c.1000G>C;p.G334R, in a family with m

69 A heterozygous missense mutation, c.2185G->A (p.G729R), in DHTKD1 has b

70 e have isolated a mouse strain with a single missense mutation, Mlkl(D139V), that alters the two-heli

71 or the pathogenicity of the newly identified missense mutation.

72 ARE harboring a retinal dystrophy-associated missense mutation.

73 ly, we analysed the effect of three clinical missense mutations (Y793C, R800C, Y849C) on catalysis, u

74 t reflects a gene's tolerance to deleterious missense mutations and serves as a useful tool to study

75 Multiple missense mutations are required to block CIF2 binding in

76 ic gliomas and bone tumors reportedly harbor missense mutations at glycine 34 in genes encoding histo

77 ost cancer-associated alterations to ATM are missense mutations at the PI3-kinase regulatory domain (

78 f this mutant (ERalpha-Q375H) and four other missense mutations at this position designed to query al

79 a beta-trefoil fold, which is susceptive for missense mutations causing alpha-dystroglycanopathies in

80 We showed that MCHS-associated missense mutations cluster in the conserved DNA binding

81 Here we show that the heterozygous missense mutations D324N, D324H and D324Y prevent caspas

82 cs-deficient mice or patients carrying PRKDC missense mutations exhibit an inflammatory gene expressi

83 ons predicted to result in loss of function; missense mutations frequently targeted the GTPase and ki

84 mutational profile is unusual; ~50 different missense mutations have been identified but no obvious l

85 evaluate the impact of four disease-causing missense mutations identified in individuals with TMEM16

86 to investigate the proteome-wide effects of missense mutations in an application that we refer to as

87 s in four of these five tumor types harbored missense mutations in at least one of the 10 Rho-GAPs.

88 Missense mutations in ATP1A3, the alpha3 isoform of Na,K

89 ominant macular dystrophy caused by over 200 missense mutations in BEST1.

90 Other spontaneous missense mutations in bfmS, such as A42E/G347D, T242R, a

91 pathogen, have naturally evolved one or more missense mutations in bfmS, which encodes the sensor his

92 Here, we show that cancer-associated missense mutations in BRG1, when placed into the ortholo

93 Missense mutations in cancers in the p53 DNA-binding and

94 B1, SRSF2, and U2AF1 are subject to frequent missense mutations in clonal hematopoiesis and diverse n

95 Heterozygous missense mutations in coatomer protein subunit alpha, CO

96 value of deep biological analysis of select missense mutations in elucidating the pathogenesis of ne

97 Three different heterozygous ASPRV1 missense mutations in four unrelated ichthyosis kindreds

98 S. aureus infections, where it develops via missense mutations in gene rpoB.

99 en that there are 255 unique disease-causing missense mutations in GLDC, of which 206 remain entirely

100 Cancer-associated missense mutations in human BRG1 (encoding the catalytic

101 r utility for precise somatic engineering of missense mutations in key cancer drivers.

102 knock-in mouse bearing one of the same Copa missense mutations in patients.

103 Somatic heterozygous missense mutations in PPP2R1A, the gene encoding the PP2

104 Here, we identified heterozygous missense mutations in single-strand binding protein 1 (S

105 SPG8-associated missense mutations in strumpellin did not rescue endosom

106 Heterozygous missense mutations in syt1 have recently been associated

107 At least 42% of missense mutations in TEM-1 were deleterious, indicating

108 ibed Mendelian autoimmune disorder caused by missense mutations in the coatomer protein complex subun

109 The condition is driven by nonsense and missense mutations in the dystrophin gene, leading to in

110 y measured the collateral fitness effects of missense mutations in the Escherichia coli TEM-1 beta-la

111 Several missense mutations in the orphan transporter FLVCR2 have

112 Missense mutations in the p53 DNA-binding domain (DBD) c

113 ain and a large number of patient-associated missense mutations in the RING domain and N-terminal reg

114 Cancer-associated missense mutations in the RING ubiquitin ligase domain a

115 Missense mutations in the RNA exosome component exosome

116 CD) of hnRNPA2 fibrillizes under stress, and missense mutations in this domain are found in the disea

117 impacts of temperature sensitivity-inducing missense mutations in two different subunits of the 26S

118 tform for recapitulating clinically relevant missense mutations in vivo.

119 They were found to have missense mutations in VPS4A, a gene coding for an ATPase

120 Duplication of LMNB1, or missense mutations increasing LMNB1 expression, are asso

121 modulators of myosin, and pathogenic myosin missense mutations influenced the proportions of these c

122 duction of two different ChAc disease-linked missense mutations into VPS13A prevents this XK-induced

123 Missense mutations of PRKDC encoding the DNA-dependent p

124 nation for the autoimmunity of patients with missense mutations of PRKDC, and suggests that cGAS-medi

125 Here, we describe hypomorphic missense mutations of scospondin, which allow Reissner f

126 Severe DDX3X missense mutations profoundly disrupt RNA helicase activ

127 he P(o) of these mutations with the proposed missense mutations revealed potential identities of the

128 Functional analysis of the three missense mutations showed impaired formation of the LMNB

129 specificity versions of CURE to create fewer missense mutations than RESCUE-S at the off-targets tran

130 tients with inactivating, homozygous SMARCA4 missense mutations who may benefit from SMARCA2-targeted

131 ients carrying a premature stop codon versus missense mutations will likely display different molecul

132 equence homologs that predicts the impact of missense mutations within any protein.

133 revealed previously uncharacterized hotspot missense mutations within the SMARCA4 helicase domain.

134 is for malfunction of disease-associated XPA missense mutations, and contribute to understanding of t

135 Almost all G6PD mutations are missense mutations, causing amino acid replacements that

136 ino acid variants (SAVs; also referred to as missense mutations, or non-synonymous Single Nucleotide

137 iking correlation between recurrent dominant missense mutations, polymicrogyria, and the most severe

138 cancer-associated and functionally relevant missense mutations, we show that although loss of PTEN l

139 cers, and the majority of TP53 mutations are missense mutations.

140 ive of the tumor types evaluated having DLC1 missense mutations.

141 mutations are more impaired than those with missense mutations.

142 Second, missense, nonsense, and frameshift alleles cause recessi

143 Functional analysis of some novel missense NOTCH1 and DLL4 variants in cultured cells demo

144 cing, we identified rare homozygous germline missense or nonsense variants in a known epigenetic regu

145 of 24 individuals with confirmed pathogenic missense or nonsense variants in TRIO.

146 l PAH, idiopathic PAH and heritable PAH with missense p.H288Y KLF2 mutation.

147 sed pore gate in NALCN where the majority of missense patient mutations cause gain-of-function phenot

148 The somatic missense point mutation c.402C>G (p.C134W) in the FOXL2

149 Within this active loop of AgRP, four human missense polymorphisms were deposited into the NIH Varia

150 The resulting missense protein change, p.(Ala273Lys), is predicted to

151 In vitro, BMP9 missense proteins demonstrated impaired cellular process

152 ed new RV associations, including disruptive missense RVs of NPC1L1 and an intergenic region near APO

153 In humans we identified a rare missense single nucleotide polymorphism in the BMP type

154 The missense single nucleotide variations (SNVs) rs142548867

155 ave been developed to predict the effects of missense single-nucleotide variants, and they are freque

156 brane domain is most frequently disrupted by missense SLC38A8 mutations.

157 non-synonymous Single Nucleotide Variants - missense SNVs or nsSNVs) for particular proteins.

158 terozygous de novo CNOT1 variants, including missense, splice site, and nonsense variants, who presen

159 hanosensing was revealed by the finding of a missense substitution (p.C492Y) associated with familial

160 A histidine missense substitution mutation at this locus in the huma

161 mia (AML), and the most common mutation is a missense substitution of serine-34 to phenylalanine (S34

162 ete loss of NHE6 expression, but how subtler missense substitutions or nonsense mutations that partia

163 tisystemic involvement was more prevalent in missense than biallelic loss-of-function variants (82-93

164 ; the affected members of family 2 carried a missense variant (c.2383G>T; p.[Val795Phe]).

165 aled nearly 2% of patients carry a very rare missense variant (minor allele frequency < 0.0001) in BR

166 A missense variant (rs1055153) located in the gene WWTR1 r

167 Interestingly, an East Asian-specific missense variant (rs671) in ALDH2 displayed a significan

168 Fine-mapping prioritized the lead common missense variant (TYR S192Y) as causal variant at the TY

169 mily 39 Member 8 (SLC39A8) gene encoding the missense variant A391T, which is associated with a varie

170 lignments involving 9990 genes and performed missense variant burden analyses to identify novel essen

171 ods predict the potential pathogenicity of a missense variant but fail to differentiate between separ

172 data for in vivo functional assays to gauge missense variant effect.

173 In contrast, ribosomes incorporating the missense variant erroneously read through UAG and UGA st

174 t and that the relatively mild effect of the missense variant identified in this study is sufficient

175 we present an example of this by studying a missense variant in a well-known autism spectrum disorde

176 ere, we functionally characterised a de novo missense variant in BDNF and seven rare variants in TrkB

177 re we demonstrate the segregation of a novel missense variant in CYLD (c.2155A>G, p.M719V) within the

178 A missense variant in ESRRB was implicated for recessively

179 psy revealed a previously unreported de novo missense variant in KCNA2, which encodes voltage-gated K

180 teration of corneal biomechanics and a novel missense variant in PRDX3.

181 A common missense variant in SLC39A8 is convincingly associated w

182 fic, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphoc

183 We investigated the effect of the missense variant in SP6 (p.(Ala273Lys)) using surface pl

184 quencing revealed a rare shared heterozygous missense variant in the F13A1 gene encoding factor XIII

185 one in-frame deletion) and one family with a missense variant inherited from the affected mother.

186 Missense variant interpretation is challenging.

187 In this study, we identified a germline missense variant of PLCD1 encoding PLCdelta1, c.1186G>A

188 neogenesis while those of cells carrying the missense variant reveal a depletion of nucleotide pools.

189 is and functional annotation prioritized the missense variant rs147647315 (R (Arg) > H (His)) as the

190 his notion is further confirmed by the human missense variant STB-R178Q, which is found in an autism

191 shift mutation in EXOSC5 and the p.Thr114Ile missense variant that were inherited in trans.

192 The missense variant Val94Met (rs17151919) in LEP was common

193 A new KCNA2 missense variant was discovered in a patient with epilep

194 A missense variant was identified in KCNQ1 (c.671C>T, p.T2

195 A likely pathogenic RYR2 missense variant was identified in the second proband, a

196 Remarkably, an exon 4 GATA6 missense variant, highly associated with extra-cardiac m

197 A de novo missense variant, p.Ser644Gly, was identified in a child

198 deletion involving exons 5-6 of EXOSC5 and a missense variant, p.Thr114Ile, that were inherited in tr

199 eneous CHD patients, we identified a de novo missense variant, PBX1:c.551G>C p.R184P, in a patient wi

200 In the presence of either missense variant, rhodopsin was sequestered to the photo

201 than 600 000 individuals identified a common missense variant, rs117618017 in the APH1B gene that res

202 h multiple cancer incidences carrying a RPL9 missense variant.

203 cribe six unrelated individuals with de novo missense variants affecting the ATPase domain of VPS4A,

204 We report three missense variants and one duplication in KIF21B in indiv

205 variants (one nonsense, one splice site, six missense variants and one in-frame deletion) and one fam

206 Putative dominant CASQ2 missense variants and the established recessive CASQ2-p.

207 guish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism.

208 These 3 missense variants are absent from gnomAD, and are locate

209 Three missense variants are associated with CRD for the first

210 syndromes, nearly 90% of clinically observed missense variants are deemed "variants of uncertain sign

211 ikely gene disrupting and predicted damaging missense variants are enriched in OCD probands (rate rat

212 of Kirrel3 function and the consequences of missense variants associated with autism and intellectua

213 molecule, and this function is attenuated by missense variants associated with autism spectrum disord

214 of inheritance appears intrinsic to certain missense variants because of their location and function

215 SCAST to foster advanced offline analysis of missense variants by a wide biological community.

216 However, some missense variants can be informative for developing a mo

217 Our findings indicate that EIF2AK2 missense variants cause a neurodevelopmental syndrome th

218 In contrast, missense variants cluster into two mutational hotspots i

219 Missense variants demonstrated a pleiotropic range of de

220 esponses to GATA6 loss of function (LoF) and missense variants during cardiomyocyte differentiation o

221 at p.R33Q and all 6 candidate dominant CASQ2 missense variants evaluated exhibited filamentation defe

222 For selected missense variants falling in enriched domains, myofilame

223 d-type DAAM2 cDNA, but not cDNA representing missense variants found in individuals with NS, rescued

224 and myoglobin, and for pathogenic and benign missense variants from ClinVar.

225 atrix, we elucidated 47 potential functional missense variants from genomic databases within ACE2/SLC

226 and compared their distribution with 76,153 missense variants from patients.

227 The two missense variants have been previously associated with I

228 The biological effects of human missense variants have been studied experimentally for d

229 rts have greatly expanded, and a plethora of missense variants identified both in patients and in the

230 i-dimensional functional dataset of 73 HNF1A missense variants identified in exomes of 12,940 individ

231 ies showed that all hypercalcemia-associated missense variants impaired heterologous expression, plas

232 ied three unrelated individuals with de novo missense variants in CDK19, encoding a cyclin-dependent

233 elated individuals with heterozygous de novo missense variants in EIF2AK1 (1/9) or EIF2AK2 (8/9).

234 three individuals with heterozygous de novo missense variants in KAT5 that affect normally invariant

235 Missense variants in Kirrel3 are repeatedly identified a

236 Here, we report that de novo missense variants in MAPK1, encoding the mitogen-activat

237 Recent studies show that pathogenic missense variants in myosin, the molecular motor of the

238 ist and protein-protein-interaction network, missense variants in NOD-like receptor family genes (NOD

239 e identified heterozygous germline or mosaic missense variants in PRKACA or PRKACB.

240 friendly web server to visualize and analyze missense variants in protein sequence and structure spac

241 Missense variants in RLIM have recently been identified

242 ripotent stem cells from three patients with missense variants in SCN8A: p.R1872>L (Patient 1); p.V15

243 urodevelopmental disorders arising from rare missense variants in synaptic genes.

244 No novel or missense variants in the AQP4 gene were found in Mexican

245 three others cases with predicted pathogenic missense variants in the FXYD gene family (FXYD1, FXYD6,

246 in human cells to identify loss-of-function missense variants in the key DNA mismatch repair factor

247 Missense variants in the MYH7-encoded MYH7 (beta myosin

248 We report rare FAM50A missense variants in the original Armfield XLID syndrome

249 Missense variants in the SCN8A voltage-gated sodium chan

250 ther suspected cases, we have identified new missense variants in the WNK1 gene clustering in the sho

251 oss-of-function (LoF) and predicted damaging missense variants in the WW domain binding protein 11 (W

252 Two missense variants in thin filament encoding genes were c

253 r signaling, whereas hypocalcemia-associated missense variants increased expression, plasma membrane

254 complete ClinVar variant set, we found that missense variants inside the identified regions are 106-

255 k of functional evidence for the majority of missense variants limits their clinical interpretability

256 Mono-allelic and bi-allelic missense variants localize to conserved residues; all bu

257 that 3 of these 6 putative dominant negative missense variants localized to an electronegative pocket

258 Frequently found heterozygous missense variants located within the homeodomain underli

259 tually develop rod dysfunction, and specific missense variants may be associated with a different phe

260 unknown or disputed; 80% of the 1,390 SCN5A missense variants observed in at least one individual to

261 Four missense variants occur in residues and protein regions

262 unctional evaluation of a large set of PALB2 missense variants of uncertain significance (VUSs).

263 assays to measure the effects of 2,695 VKOR missense variants on abundance and 697 variants on activ

264 ts the effects of disease-associated Kirrel3 missense variants on synapse formation, and thereby, inc

265 Surprisingly, a few SMARCA4 missense variants partially or fully rescued paralog dep

266 tion was performed with VIPUR for all WNT10A missense variants reported in the Exome Aggregation Cons

267 Finally, 25% of human VKOR missense variants show reduced abundance or activity, po

268 Twelve missense variants showed strong evidence of pathogenicit

269 rate, in vivo, that the expression of KIF21B missense variants specifically recapitulates patients' n

270 ng embryogenesis, and NADSYN1 has bi-allelic missense variants that cause NAD deficiency-dependent ma

271 Numerous C-Pro missense variants that disrupt or delay triple-helix for

272 As proof of concept, we functionalized 47 missense variants using this assay, only 19 of which hav

273 The large majority (89%) of missense variants were functionally neutral, perhaps une

274 Two previously reported and two novel CYB5R3 missense variants were identified among the methemoglobi

275 East Asian-specific missense variants were identified as candidate causal va

276 Individuals carrying missense variants with drastically reduced FANCD2 monoub

277 These findings suggest that novel missense variants within the helicase domain of BRIP1 ma

278 onsense/frameshift variants and 12 different missense variants) in 38 unrelated individuals, 21 of wh

279 s, we functionally characterized 20 of these missense variants, focusing on the altered protein's abi

280 in BRIP1, genetic testing more often reveals missense variants, for which the impact on molecular fun

281 erpretation of the molecular-level effect of missense variants, however, remains challenging and requ

282 identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, an

283 Missense variants, instead, have often been undervalued.

284 For FANCB missense variants, more variable severity is associated

285 odeling and machine learning classifies PTEN missense variants, over 70% of which are currently liste

286 Functional assessments of NADSYN1 missense variants, through a combination of yeast comple

287 by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding

288 cript destabilization were associated with 2 missense variants.

289 ow signals of selection equivalent to coding missense variants.

290 nd three with potentially disruptive de novo missense variants.

291 dynamics in determining the pathogenicity of missense variants.

292 h earlier onset of dystonia) than those with missense variants.

293 clinically interpreted pathogenic and benign missense variants.

294 r functional disruption is occurring in both missense variants.

295 unknown function that is commonly altered by missense variants.

296 transfected with plasmids that express FAF1 missense variants.

297 ate between pathogenic and putatively benign missense variants.

298 uanines of UTR pG4s is comparable to that of missense variation in protein-coding sequences.

299 nce of the effect of amino acid-substituting missense variations on protein structure and function be

300 tional evidence to resolve the ~1,300 extant missense VUSs in MSH2 and may facilitate the prospective