GEPHE SUMMARY Print
Gephebase Gene
Entry Status
Published
GepheID
GP00001515
Main curator
Prigent
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Artemisinin-sensitive Plasmodium with mean parasite clearance half-life of 2.6 hours
Trait State in Taxon B
Artemisinin-resistant Plasmodium with mean parasite clearance half-life of 6.13 hours from Thailand (1 sample) and Cambodia (2 samples)
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Common Name
malaria parasite P. falciparum
Synonyms
Plasmodium (Laverania) falciparum; malaria parasite P. falciparum
Rank
species
Lineage
cellular organisms; Eukaryota; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; Plasmodiidae; Plasmodium; Plasmodium (Laverania)
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
malaria parasite P. falciparum
Synonyms
Plasmodium (Laverania) falciparum; malaria parasite P. falciparum
Rank
species
Lineage
cellular organisms; Eukaryota; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; Plasmodiidae; Plasmodium; Plasmodium (Laverania)
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
PF3D7_1343700
Synonyms
PF3D7_1343700
String
-
Sequence Similarities
-
GO - Molecular Function
-
GO - Cellular Component
-
UniProtKB
Plasmodium falciparum (isolate 3D7)
GenebankID or UniProtKB
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
A481V affecting the encoded propeller domain
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid - - -
Authors
Miotto O; Amato R; Ashley EA; MacInnis B; Almagro-Garcia J; Amaratunga C; Lim P; Mead D; et al. ... show more
Abstract
We report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin, the frontline antimalarial drug. Across 15 locations in Southeast Asia, we identified at least 20 mutations in kelch13 (PF3D7_1343700) affecting the encoded propeller and BTB/POZ domains, which were associated with a slow parasite clearance rate after treatment with artemisinin derivatives. Nonsynonymous polymorphisms in fd (ferredoxin), arps10 (apicoplast ribosomal protein S10), mdr2 (multidrug resistance protein 2) and crt (chloroquine resistance transporter) also showed strong associations with artemisinin resistance. Analysis of the fine structure of the parasite population showed that the fd, arps10, mdr2 and crt polymorphisms are markers of a genetic background on which kelch13 mutations are particularly likely to arise and that they correlate with the contemporary geographical boundaries and population frequencies of artemisinin resistance. These findings indicate that the risk of new resistance-causing mutations emerging is determined by specific predisposing genetic factors in the underlying parasite population.
Additional References
COMMENTS
YOUR FEEDBACK is welcome!