rs28362286

This is a stop gained variant in the PCSK9 gene.

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GWAS Catalog Trait Associations (11)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

low density lipoprotein cholesterol measurement

Graham SE et al. “The power of genetic diversity in genome-wide association studies of lipids.” Nature 600(7890):675-679 (2021)
Allele A
OR 1.08
p —
N 99,432
Large GWAS
African American or Afro-Caribbean, African unspecified
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.88
p 1.0e-253
N 578,955
Major Consortium StudyLarge GWAS
multi-ancestry
Gurdasani D et al. “Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.” Cell 179(4):984-1002.e36 (2019)
Allele A
OR 0.85
p 2.0e-42
N 14,126
Large GWAS
Sub-Saharan African
Choudhury A et al. “Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits.” Nature Communications 13(1):2578 (2022)
Allele A
OR 0.94
p 4.0e-73
N 10,389
Meta-analysisLarge GWAS
Sub-Saharan African

hyperlipidemia

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele C
OR 1.14
p 5.0e-102
N 114,081
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

metabolic disease

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele C
OR 1.14
p 8.0e-102
N 114,061
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

non-high density lipoprotein cholesterol measurement

Graham SE et al. “The power of genetic diversity in genome-wide association studies of lipids.” Nature 600(7890):675-679 (2021)
Allele A
OR 1.00
p 3.0e-84
N 99,432
Large GWAS
African American or Afro-Caribbean, African unspecified

Hypercholesterolemia

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele C
OR 1.30
p 2.0e-66
N 55,505
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

drug use measurement, Hypercholesterolemia

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele C
OR 1.23
p 7.0e-48
N 55,505
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

Hyperlipidemia

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele C
OR 0.59
p 5.0e-15
N 112,369
Major Consortium StudyLarge GWAS
African American or Afro-Caribbean

proprotein convertase subtilisin/kexin type 9 measurement

Surapaneni A et al. “Identification of 969 protein quantitative trait loci in an African American population with kidney disease attributed to hypertension.” Kidney International 102(5):1167-1177 (2022)
Allele A
OR 1.88
p 3.0e-14
N 466
Small GWAS
African American or Afro-Caribbean

metabolite measurement

Tahir UA et al. “Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals.” Nature Communications 13(1):4923 (2022)
Allele A
OR 1.01
p 4.0e-13
N 2,466
Large GWAS
multi-ancestry
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ClinVar annotation

Pathogenic★☆☆☆
11 submitters23 publications

Cardiovascular phenotype; Familial hypercholesterolemia; Hypercholesterolemia, autosomal dominant, 3 (FHCL3); Hypocholesterolemia; Low density lipoprotein cholesterol level quantitative trait locus 1 (LDLCQ1); PCSK9-related disorder; not specified

View on ClinVar →

About PCSK9

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

View all PCSK9 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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