The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population
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Updated: Jul 19, 2026

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
Amanda J Hooper1, A David Marais, Donald M Tanyanyiwa
1Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia.
Objective:
Missense mutations in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) can cause familial hypercholesterolemia. However, two nonsense variants of PCSK9, Y142X and C679X, found in approximately 2% of black American subjects, are associated with a 28% reduction in mean low density lipoprotein (LDL)-cholesterol. We sought to determine the frequency and effect of these nonsense variants in an African population.
Methods And Results:
PCSK9 genotypes were determined in 653 black African women attending two antenatal clinics in Zimbabwe. C679X occurred in 3.7% of subjects and was associated with a 27% reduction in LDL-cholesterol (1.6+/-0.3 mmol/L versus 2.2+/-0.7 mmol/L in non-carriers). We did not observe the Y142X variant.
Conclusions:
Our results show that the PCSK9 C679X variant has a marked cholesterol-lowering effect.
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