A single nucleotide polymorphism in the Plasmodium falciparum atg18 gene associates with artemisinin resistance and confers enhanced parasite survival under nutrient deprivation

Table 1 SNPs in autophagy-related genes from the Tracking Resistance to Artemisinin Collaboration (TRAC) study

Gene	Annotation	Protein	Position	Amino acid change	Mutation type	p value	Phenotype
PF3D7_1343700	Kelch protein K13	Kelch13	1,725,259	X	N	4E−26	Parasite clearance half-life
PF3D7_1012900	Autophagy-related protein 18 (Atg18), putative	Atg18	497,461	T38I	N	5.89E−07	Parasite clearance half-life
PF3D7_1239800	Conserved Plasmodium protein, unknown function	Atg11	1,669,294	D2948E	N	3.92E−05	Parasite clearance half-life
PF3D7_1012900	Autophagy-related protein 18 (Atg18), putative	Atg18	497,461	T38I	N	0.0002	Chloroquine IC₅₀
PF3D7_1239800	Conserved Plasmodium protein, unknown function	Atg11	1,670,910	N3487S	N	0.0002	Parasite clearance half-life
PF3D7_0709400	Cg7 protein	Atg14	426,753	V161E	N	0.0007	Chloroquine IC₅₀
PF3D7_1239800	Conserved Plasmodium protein, unknown function	Atg11	1,674,565	N4705K	N	0.0007	Piperaquine IC₅₀
PF3D7_1126100	ThiF family protein, putative	Atg7	1,018,965	1177C	S	0.0044	Chloroquine IC₅₀
PF3D7_1126100	ThiF family protein, putative	Atg7	1,018,965	1177C	S	0.0129	Quinine IC₅₀

Proteins listed are putative proteins as annotated by PlasmoDB or through BLAST searches. Kelch13 has been included as a reference, since polymorphisms in this gene have been previously associated with drug resistance phenotypes. The amino acid change for Kelch13 is denoted as “X” to represent several different SNPs that have been found within this gene. Mutation types “N” and “S” indicate non-synonymous and synonymous mutations, respectively. The p values are unadjusted for multiple comparisons. All SNPs that associated with long parasite clearance half-life in the TRAC study were published by Miotto et al. [6]

ISSN: 1475-2875