Atherogenic Lipoproteins

Intronic variant strongly associated with elevated lipoprotein(a) levels and significantly increased risk of coronary artery disease and aortic valve stenosis

Loss-of-function variant that naturally lowers LDL cholesterol by 15-28% and reduces coronary disease risk by up to 47%

Missense variant in the SCAP cholesterol-sensor gene (Val798Ile); the C allele (coding-strand G) impairs the SCAP–SREBP-2 feedback axis, promoting cholesterol accumulation in vascular cells and elevating sudden cardiac death risk in combination with the SREBF2 Gly595Ala variant

The most severe gain-of-function PCSK9 mutation, increasing LDLR-binding affinity 10-25-fold to cause extreme LDL elevation and early-onset coronary artery disease in carriers of this rare pathogenic variant

LDLR missense variant at position 827 within the cytoplasmic NPXY internalization motif; classified as uncertain significance for familial hypercholesterolemia, with conflicting functional and population evidence — the more common G>A change (Val827Ile) shows no LDL uptake impairment in functional assays, while the rarer G>T change (Val827Phe) has been reported in FH patients

Regulatory variant ~2kb upstream of ABCG1 that modulates transporter expression in macrophages; the G allele is associated with reduced risk of ischemic stroke, particularly the atherothrombotic subtype, likely through effects on HDL-mediated cholesterol clearance from arterial plaques

Promoter variant that reduces hepatic lipase activity, raising HDL-C levels but shifting to larger, less protective HDL particles with a genotype-specific dietary fat response

Missense variant in APOH (beta-2-glycoprotein I) that disrupts the phospholipid-binding domain, reducing the protein's capacity to act as an autoantigen in antiphospholipid syndrome

Intergenic tag SNP 7.3 kb downstream of ASGR1; the rare A allele proxies the ASGR1 del12 loss-of-function variant (r²=0.86) and associates with ~13 mg/dL lower non-HDL cholesterol and a 34% reduced risk of coronary artery disease

Intronic tag SNP in the DOCK7/ANGPTL3 region; the T allele is associated with higher fasting triglycerides, higher LDL cholesterol, and elevated cardiovascular risk through reduced ANGPTL3-pathway LPL activity

Gain-of-function PCSK9 missense variant (Ser127Arg) causing autosomal dominant familial hypercholesterolemia through enhanced LDL receptor degradation; rare but highly penetrant, carriers have severely elevated LDL-C and premature coronary artery disease

Missense variant in the protease-like domain of apolipoprotein(a) causing markedly elevated Lp(a) levels and substantially increased risk of coronary artery disease, peripheral vascular disease, and aortic valve stenosis; carriers show differential benefit from aspirin therapy

3'UTR variant in the ATP-binding cassette transporter A1 gene; the G allele (homozygous GG) is enriched in ischemic stroke patients and associates with lower total cholesterol, suggesting impaired cholesterol efflux capacity may elevate cerebrovascular risk

3'UTR variant that creates a microRNA-4271 binding site; the T allele suppresses APOC3 translation, lowering triglycerides and modestly reducing coronary heart disease risk

Intronic PPARA variant whose minor G allele has been associated with modest myocardial infarction risk and may influence the gene's anti-inflammatory transcriptional activity in vascular tissue

Common missense variant in PCSK9 exon 12 where the rare G allele raises LDL cholesterol and increases coronary artery disease risk through enhanced LDLR degradation

Regulates triglyceride metabolism through effects on APOC3 expression in the 3'UTR

Missense variant in LRP8 (ApoER2) replacing arginine with glutamine at position 952; the Q allele contributes to the TACGC risk haplotype linked to early-onset familial myocardial infarction, elevated triglycerides, and altered platelet reactivity via impaired apolipoprotein E signaling

3'UTR variant in LRP8 (ApoER2) that affects mRNA stability and forms part of the TACGC cardiovascular risk haplotype associated with premature myocardial infarction and coronary artery disease

Synonymous coding variant (Lys89Lys) in the asialoglycoprotein receptor 1 gene that acts as an sQTL and eQTL, reducing ASGR1 expression and associating with lower LDL and non-HDL cholesterol at genome-wide significance and reduced coronary artery disease risk

Synonymous variant in LDLR exon 13 that modulates mRNA splicing efficiency in concert with rs688, influencing LDL receptor levels and LDL-cholesterol concentrations

Regulatory PPARA variant where TT homozygotes with type 2 diabetes experience a 51% reduction in major cardiovascular events when treated with fenofibrate, while C-allele carriers show no cardiovascular benefit from the drug

Common regulatory variant in the LDL receptor gene affecting LDLR expression, baseline LDL cholesterol levels, and statin response

Promoter variant that reduces APOA5 expression, impairing lipoprotein lipase activity and raising triglycerides by 15–36%; major determinant of hypertriglyceridemia and dietary fat response

Synonymous LDLR variant that disrupts exon 12 splicing, reduces LDL receptor surface expression by ~22%, and raises LDL cholesterol — particularly in pre-menopausal women

Silent variant affecting LDL particle number and lipid metabolism; A allele carriers have higher ApoB, LDL-C, and total cholesterol levels

Influences HDL cholesterol levels and particle size through effects on cholesterol ester transfer protein activity

Rare likely-pathogenic missense variant in the LDLR EGF-like repeat domain causing impaired LDL receptor processing and familial hypercholesterolemia with severely elevated LDL-C and premature coronary artery disease risk

Rare LDLR missense variant (c.1570G>A, p.Val524Met) associated with familial hypercholesterolemia; classified as likely pathogenic by the British Heart Foundation LDLR-LOVD registry

Rare pathogenic nonsense variant in the LDL receptor gene that abolishes receptor function, causing receptor-negative familial hypercholesterolemia with severely elevated LDL-C and high premature coronary artery disease risk