IndraLab

Statements

KCNG1 binds hyd WA. 91 / 91
| 91
sparser
"The K13-propeller gene polymorphisms associated with decreased artemisinin parasite clearance reported in Southeast Asia include C580Y, R539T, R543I, and Y493H [ xref ]."
30447701
sparser
"The increased K13-propeller gene mutations previously associated with DPC among P. falciparum populations from 2013 to 2014 in Grande Comore (a ~20 % increment) may present new challenges in the ACT efficacy in the future [ xref , xref ]."
27527604
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"Out of the 13 samples suspected of recrudescence, 5 (38%) samples were positively amplified as P. falciparum, with polymorphisms in the k13-propeller gene detected."
36894982
sparser
"Although wide-scale studies that analyzed P . falciparum isolates from numerous sub-Saharan African countries including Ethiopia found no mutations in the parasite’s K13-propeller gene, which is associated with artemisinin resistance in Southeast Asia [ xref , xref ] the threat is clear."
28445503
sparser
"However, resistance has been shown to occur primarily during the ring stage of parasite development due to multiple forms of mutations in the Kelch PF3D7_1343700 (K13-propeller) helix domain on chromosome 13 [70]."
34797496
sparser
"Our observation is consistent with those in previous reports from Kenya [ xref ], Angola [ xref ], Mozambique [ xref ], Senegal [ xref ], Ugandan [ xref ] as well as other areas of Sub-Saharan Africa [ xref ], Caribbean’s Haiti [ xref ], and South Asia’ Bangladesh [ xref ], where the K13-propeller gene mutations associated with artemisinin resistance were absent."
26667053
sparser
"Whereas there is the most reliable evidence linking mutations in the Kelch domain protein (K13-propeller; PF3D7_1343700) with parasite tolerance to artemisinin [ xref ], insufficient knowledge on the molecular mechanisms of artemisinin action hampers a definitive conclusion."
| PMC
sparser
"Molecular surveillance of K13-propeller polymorphism has been recommended as a complementary tool to evaluate the presence of artemisinin resistance in malaria pandemic countries."
32677899
sparser
"To confirm that K13-propeller polymorphism is a molecular marker of clinical artemisinin resistance, parasite-clearance half-lives in patients were correlated with their K13 alleles."
| PMC
sparser
"In the few reported cases of recrudescence after ACT treatment, parasite samples did not carry mutations in the K13-propeller domain [ xref ]."
33770151
sparser
"Meanwhile, artemisinin tolerance in vitro was associated with the M476I mutation of K13-propeller [ xref ]."
26667053
sparser
"Genomic DNA of Plasmodium falciparum was extracted from the blood samples, and polymorphisms of pfcrt, pfmdr1, and K13-propeller were analyzed with nested PCR amplification followed by sequencing."
32677899
sparser
"These strains included P. falciparum CamWT_C580Y, a K13-propeller mutant associated with increased resistance to artemisinin; Dd2, resistant to chloroquine, pyrimethamine and mefloquine; GB4, resistant to chloroquine; and SB1-A6, resistant to inhibitors of cytochrome bc1 electron transport such as atovaquone xref ."
29670144
sparser
"Although several mutations in the k13-propeller gene were detected, no widespread artemisinin-resistant polymorphisms were reported."
| PMC
sparser
"Only polymorphisms of a gene, K13-propeller, showed a significant association with RSA0–3 h survival rates."
| PMC
sparser
"WHO validated polymorphisms in the k13-propeller gene previously reported to be associated with ACT resistance were not detected in the P. falciparum isolates from Kisii County, Kenya."
36894982
sparser
"Mutations in the K13-propeller lead to an increase in phosphatidylinositol-3-kinase (PfPI3K), which is required to mediate cell signalling and survival [71]."
34797496
sparser
"The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller (pfk13) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study."
34758836
sparser
"All isolates had wild-type K13-propeller sequences."
33289466
sparser
"Mutations in a Kelch domain protein (K13-propeller; PF3D7_1343700) are associated with decreased ART sensitivity in vitro; xref and genetic manipulation of the K13 locus has confirmed a role in the decreased sensitivity phenotype, although other genetic factors also contribute xref ."
30228310
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"The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC)"
32822392
sparser
"It has been suggested that Y493H, I543T, R539T, and C580Y mutations in K13-propeller gene are associated with prolonged parasite survival ex vivo; Y493H, R539T, and C580Y mutations are linked to in vivo delayed parasite clearance; and M476I mutation is related to artemisinin tolerance in vitro [ xref , xref , xref , xref ] ."
26667053
sparser
"In total, four mutant alleles, each harboring a single nonsynonymous SNP (Y493H, R539T, I543T, and C580Y) within a kelch repeat of the C-terminal K13-propeller domain were identified."
| PMC
sparser
"In GrpA, artemisinin resistance and K13-propeller polymorphisms also associated with down-regulation of genes involved in DNA replication ( xref and xref )."
25502316
sparser
"In addition, three nonsynonymous mutations (S459T, C469F, and V692L) and two synonymous mutations (R471R and V589V) were detected in K13-propeller, all having prevalence less than 6.0%."
32677899
sparser
"Furthermore, molecular surveillance in Dakar has demonstrated the emergence of polymorphisms in the K13 propeller domain gene, which is associated with in vitro and in vivo resistance to artemisinin in Asia [ xref – xref ]."
27387549
sparser
"These observations suggest that not all K13-propeller mutations are associated with artemisinin resistance, and that secondary loci are involved in resistance Asian parasites, but not in African parasites."
26667053
sparser
"Not only is the emergence and spread of ART-resistant isolate in South East Asian regions a matter of concern but also the occurrence of low-frequency candidate mutations in the k13-propeller gene across certain regions of North-Eastern India could draw the state of Odisha's attention."
32258150
sparser
"K13-propeller gene polymorphisms in Plasmodium falciparum: the lack of Artemisinin resistance markers in the Democratic Republic of Congo"
32822392
sparser
"Numerous independent K13 propeller mutations associated with resistance have emerged independently across the region ( xref , xref ), and the frequencies of some mutations, notably, Cys580Tyr, have risen in multiple geographical areas."
28137815
sparser
"K13-propeller mutation was identified as a key determinant of artemisinin resistance in Southeast Asia [ xref ]."
31856172
sparser
"The role of the A578S amino acid substitution is unclear, but it occurs near the most common K13-propeller mutation (C580Y), which has been associated with delayed parasite clearance in Southeast Asia and with tolerance to artemisinin in vitro ( xref )."
26079933
sparser
"Recently association of K13-propeller polymorphism with artemisinin resistance in vitro and in vivo has been proposed [ xref ]."
25052385
sparser
"In this study, we set out to evaluate polymorphisms of pfcrt , pfmdr1 , and K13-propeller genes in imported falciparum malaria cases from Africa, in order to provide guidance on antimalarial drug administration for the local government of Guizhou Province."
32677899
sparser
"It has been widely accepted that pfcrt, pfmdr1 , and K13-propeller are candidate genes for resistance to anti-malarial drugs [ xref , xref , xref ]."
32677899
sparser
"However, in Southeast Asia, decreased parasite sensitivity to artemisinin agents associated with polymorphisms in the parasite K13-propeller gene has been reported [ xref , xref ]."
30447701
sparser
"Mutations in the P. falciparum k13 gene that encodes the kelch propeller domain were associated with in vitro resistance to artemisinin and with delayed clearance after artemisinin treatment in Southeast Asia [ xref , xref – xref ]."
25471113
sparser
"Slow parasite clearance, absent K13-propeller gene polymorphisms and adequate artesunate levels among patients with malaria: A pilot study from southern India."
32769239
sparser
"The sensitivity and specificity of this definition may be enhanced by using only the subset of K13 -propeller mutations that have been associated with artemisinin resistance in clinical and in vitro studies, or combining them with other molecular markers."
27776514
sparser
"Interestingly, a cluster of seven mutants were identified that were sensitive to artemisinin, including one with a mutation in the K13-propeller gene that is associated with resistance xref , xref , xref ."
27803804
sparser
"To our knowledge, this is the first work providing information on the prevalence of k13-propeller and pfmdr1 mutations from Sédhiou, a region in the south of Senegal."
33770151
sparser
"One member of the superfamily of Kelch-repeat protein, which the K13-propeller protein belongs to, human KEAP1, binds to ubiquitin ligase E3 and a ubiquitination substrate transcription factor at each binding site ( xref ), suggesting that the K13-propeller protein of P. falciparum may also function as an adapter protein that controls the nuclear binding of a stress response transcription factor through ubiquitination and proteosome degradation ( xref )."
35004357
sparser
"Knowledge of mutations in the k13-propeller (Pfk13) gene associated with slow clearance of artemisinin derivatives, provides the ability to track and prevent spread, and assess the effectiveness of control measures."
30883571
sparser
"This is in line with recent observations in Senegal, where most of the samples were also wild type for K13-propeller domain [ xref , xref , xref ]."
33770151
sparser
"Baseline parasitaemia was associated with the K13-propeller mutation ( P value = 0.37 [linear regression, adjusted for site])."
28086775
sparser
"Our analysis revealed that all but 6 of the isolates carried wild type K13-propeller."
33770151
sparser
"Genome-wide association studies of the P. falciparum whole genome sequencing data have identified a gene named PfKelch13- PF3D7-1343700 locating on chromosome 13 which encodes K13-propeller protein."
32258150
sparser
"In addition, mutations in the P. falciparum K13 gene (PF3D7_1343700) that encodes the kelch propeller domain were associated with in vitro resistance to artemisinin and with delayed clearance after artemisinin treatment in southern Asia [ xref , xref , xref ]."
25849097
sparser
"In areas outside Southeast Asia, K13-propeller gene polymorphisms different from those detected and validated in Cambodia have been reported [ xref ]."
30447701
sparser
"Sequences for the K13-propeller domain were generated successfully for all the samples analysed in this study."
34906159
sparser
"This study was aimed to analyze the polymorphisms of pfcrt, pfmdr1, and K13-propeller among imported falciparum malaria cases in Guizhou Province, China."
32677899
sparser
"The study also investigated the prevalence of K13-propeller polymorphisms across different hemoglobin genotype groups."
34569928
sparser
"Both transcriptional phenotypes are closely associated with K13-propeller polymorphism, and may enable parasites to survive artemisinin by repairing and replenishing their oxidatively-damaged proteins before advancing through the cell cycle."
27337450
sparser
"However, resistance has been shown to occur primarily during the ring stage of parasite development due to multiple forms of mutations in the Kelch PF3D7_1343700 (K13-propeller) helix domain on chromosome 13 [ xref ]."
34797496
sparser
"Unfortunately, there is no alternative to the current regimen ACT for the severe uncomplicated malaria and also no significant research has yet been done on K13-propeller polymorphism; hence, it is essential to monitor the efficacy of the Artemisinin derivative through molecular surveillance study in the selected areas of the state during the year 2018."
32258150
sparser
"There has been no systematic review done to date on the K13-propeller gene polymorphisms being reported among P. falciparum parasites in Africa and other malaria-endemic areas outside Southeast Asia."
30447701
sparser
"The identification of isolates with increased ex vivo RSA rates in the absence of K13-propeller mutations and no positivity at day three requires further investigation."
33289466
sparser
"The presence of K13 propeller mutations within Africa, where parasite clearance is generally rapid, suggests that not all K13 propeller mutations are associated with resistance, that secondary loci are involved in resistance and found in Asia but not in Africa thus far, or that the resistance phenotype is masked by high levels of antimalarial immunity."
25891142
sparser
"The K13-propeller mutations associated with artemisinin-resistance were mainly found in Southeast Asia, with C580Y being the predominant one."
28797235
sparser
"K13-propeller mutations confer artemisinin resistance in plasmodium falciparum clinical isolates."
| DOI
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"Polymorphisms of pfcrt, pfmdr1, and K13-propeller genes in imported falciparum malaria isolates from Africa in Guizhou province, China."
32677899
sparser
"Despite the diversity of the identified mutations in the k13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected."
33168025
sparser
"A study by Ariey et al [ xref ] validated K13-propeller gene polymorphisms in Plasmodium falciparum parasites associated with delayed parasite clearance by artemisinin agents."
30447701
sparser
"Major mutations in the K13 propeller domain associated with artemisinin resistance in the Mekong region (C580Y, R539T and Y493H) were absent, but F446I and two previously undescribed mutations (V603E and V454I) were identified."
30883571
sparser
"This is the first study designed to analyse the prevalence of polymorphism in the P. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic."
33168025
sparser
"Although K13-propeller mutations previously associated with delayed parasite clearance in Cambodia were not identified, 26 K13-propeller mutations were identified in both recent samples and pre-ACT infections."
25918205
sparser
"Many administrative regions in Myanmar had combined K13-propeller mutation prevalence of more than 20% [ xref ], including regions on the Myanmar India border areas."
31856172
sparser
"One member of the superfamily of Kelch-repeat protein, which the K13-propeller protein belongs to, human KEAP1, binds to ubiquitin ligase E3 and a ubiquitination substrate transcription factor at each binding site (Tilley et al., 2016), suggesting that the K13-propeller protein of P. falciparum may also function as an adapter protein that controls the nuclear binding of a stress response transcription factor through ubiquitination and proteosome degradation (Tilley et al., 2016)."
35004357
sparser
"SNPs of K13-propeller."
32677899
sparser
"F32-DU whole genome sequencing (WGS) revealed that resistance to trioxaquine was associated with the same non-synonymous mutation in the propeller domain of the K13 protein (M476I) that was found in the F32-ART lineage."
29177421
sparser
"We found low prevalence of K13 propeller domain mutations, which are associated with artemisinin resistance in Asia, but one mutation previously identified in northern Uganda, 675V, was seen in 2.0% of samples, including 5.5% from the 3 northernmost sites."
30559133
sparser
"DNA sequencing of artemisinin-resistant strains showed that there were 9 meaningful mutations at P. berghei K13-propeller domain, but the above mutations did not include common clinical point mutations."
36386414
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"Polymorphisms in the K13-Propeller Gene in Artemisinin-Resistant Plasmodium in Mice."
36386414
sparser
"385 The copyright holder for this this version postedDecember 11, 2021. ; https://doi.org/10.1101 https://doi.org/10. /2021 resistance (K13-propeller sequence polymorphisms)."
| DOI
sparser
"In addition, multiple studies report K13-propeller gene polymorphisms different from those validated for causing artemisinin resistance in Southeast Asia."
30447701
sparser
"The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller ( pfk13 ) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study."
| PMC
sparser
"The studies reported here were conducted to assess the efficacy of these artemisinin-based combinations and the mutations in Plasmodium falciparum K13-propeller ( Pfk13 ) domain and amplification in Pfplasmepsin 2 ( Pfpm2 ) gene in Somalia."
31296223
sparser
"It needs to be confirmed whether parasites harbouring both K13 mutation and pfmdr1 multiple copies and/or the observed new mutations of K13 propeller domain are associated with clinical artemisinin resistance."
31239407
sparser
"Non-synonymous mutations in the kelch propeller domain (K13-propeller) in Plasmodium falciparum have been associated with artemisinin resistance in samples from Southeast Asia ( xref )."
32201636
sparser
"In Africa, K13-propeller genotyping confirms the emergence of the R561H mutation in Rwanda and highlights the continuing dominance of wild-type K13 elsewhere."
34279219
sparser
"To help establish a more sensitive and specific method for the detection of P. ovale genes, this study performs sequence analysis on k13-propeller polymorphisms in P. ovale."
32660505
sparser
"Mutations in the K13-propeller lead to an increase in phosphatidylinositol-3-kinase (PfPI3K), which is required to mediate cell signalling and survival [ xref ]."
34797496
sparser
"A mutant K13 propeller domain has now been associated with artemisinin resistance in Cambodia and in the Greater Mekong Region ( xref – xref , xref , xref )."
26401601
sparser
"Genomic analysis of Cambodian parasite isolates have identified four prevalent K13-propeller mutations (Y493H, R539T, I543T, and C580Y) that are associated with elevated ring-stage survival rates In vitro and long parasite clearance half-lives (>5 h) [ xref ]."
27543172
sparser
"Specifically, three mutations (C580Y, R539T and Y493H) in the K13-propeller gene were strongly associated with increased ring stage survival and delayed parasite clearance [ xref ]."
26667053
sparser
"A nested PCR was performed on each sample to amplify the K13-propeller domain, corresponding to codons 440-680."
| DOI
sparser
"Each patient's parasite isolate was assessed for ex vivo RSA, K13-propeller mutations, pfmdr1 copy number, and pfmdr1 mutations at codons 86, 184, 1034, 1042, and 1246, associated with reduced susceptibility, and 50% inhibitory concentration (IC 50 ) for other antimalarial drugs."
33289466
sparser
"However, this success has been threatened by the development of P. falciparum parasites with delayed clearance in response to ACT therapy and their spread throughout Southeast Asia to East India. xref – xref More recently, delayed clearance in response to artemisinin has been reported in parasites from sub-Saharan Africa that lack mutations in the K13-propeller domain protein, which had been associated with delayed clearance by artemisinin-based drugs in southeast Asia. xref , xref The emergence and spread of parasites with delayed clearance to artemisinin treatment makes it imperative to develop new antimalarial drugs against novel therapeutic targets. xref – xref In the current work we utilized a target-based approach to identify small molecule inhibitors that target the malaria parasite purine import pathway."
31373203
sparser
"To our knowledge, this is the first work providing information on the prevalence of k13-propeller and pfmdr1 mutations in Sédhiou, a region in the south of Senegal."
33770151
sparser
"Interestingly, evidence has associated the K13-propeller protein with ubiquitination [ xref , xref ], and inhibitors of the UPS have been shown to enhance the action of artemisinin against the P. falciparum parasites [ xref , xref , xref ]."
| PMC
sparser
"Based on Keap1 function, a hypothetical model could be that in steady state conditions, the wild-type K13-propeller domain binds to uTF (a putative, unidentified transcription factor functionally equivalent to human Nrf2) allowing its ubiquitination and proteosomal degradation."
26955948