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PCSK9

Proprotein convertase subtilisin/kexin type 9

Gene Number: 255738

Location: 1p32.3

Key Functions: LDL receptor regulation, cholesterol clearance, lipid metabolism


PCSK9 helps regulate how much LDL cholesterol remains in your bloodstream. Its protein promotes the breakdown of LDL receptors—the receptors liver cells use to remove LDL particles from the blood. Lower PCSK9 activity leaves more receptors available to clear LDL cholesterol [R].


This report examines rs11591147, also called R46L.


Explore your genotype below, or visit our APOB and cholesterol transport and APOE and lipid metabolism reports to view other genetic influences on cholesterol.

SNP ID
Your Genotype
Alt Allele
Interpretation
rs11591147
Analyze your DNA to see your genotype
T
Analyze your DNA to see a personalized result.

rs11591147 — R46L and LDL Cholesterol

  • GG – Common genotype. No copies of the LDL-lowering R46L variant. This result does not mean your cholesterol is high [R].

  • GT – One T allele. Associated with reduced PCSK9 function, lower LDL cholesterol and lower coronary heart disease risk [R].

  • TT – Two T alleles. A rare genotype associated with lower LDL cholesterol, with a greater LDL reduction observed than in GT carriers [R].

Functional effect: R46L replaces arginine with leucine at position 46 of the PCSK9 protein. This reduces its ability to promote LDL receptor breakdown, helping the liver remove more LDL cholesterol from circulation [R].


How Large Is the Effect?

A Danish study involving 103,083 people reported median LDL cholesterol levels of:

  • GG: 124 mg/dL.

  • GT: 104 mg/dL.

  • TT: 97 mg/dL.

When GT and TT carriers were combined, they had approximately 23% lower odds of myocardial infarction (heart attack) compared with GG noncarriers [R]. Your genotype helps explain an inherited tendency; a lipid blood test measures your actual cholesterol levels.


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