K76T

K76T is a point mutation in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene, in which the amino acid lysine (K) at codon 76 is replaced by threonine (T). This substitution is the best-characterized genetic change linked to chloroquine resistance in P. falciparum, the parasite responsible for the most severe form of human malaria.

The pfcrt-76T mutation alters the function of the PfCRT transporter, which resides in the digestive vacuole membrane of the parasite. By changing the transport properties of this membrane protein, the parasite reduces the accumulation of chloroquine at the drug’s site of action, enabling survival at drug concentrations that would normally be lethal.

K76T resistance is commonly found in haplotypic backgrounds such as CVIET and SVMNT, and it frequently co-occurs with additional mutations in pfcrt (notably at codons 72–75) and with polymorphisms in pfmdr1. These accompanying changes can modulate resistance levels and patterns of susceptibility to other antimalarial drugs, thus influencing regional treatment outcomes and surveillance interpretations.

In practice, K76T serves as a key molecular marker in the surveillance of chloroquine resistance. Its presence in parasite populations correlates with reduced efficacy of chloroquine, contributing to shifts in malaria treatment policy, including widespread adoption of artemisinin-based combination therapies. Although chloroquine use has declined in many regions, monitoring K76T and related pfcrt mutations remains important for understanding parasite population dynamics and drug resistance trends.