rs28362263

This is a variant in the PCSK9 gene that changes a alanine to an threonine.

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GWAS Catalog Trait Associations (4)

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

total cholesterol measurement

Kamiza AB et al. “Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry.” Nature Communications 14(1):5403 (2023)
Allele A
OR 0.13
p 1.0e-88
N 125,000
Large GWAS
African American or Afro-Caribbean, Sub-Saharan African, African unspecified
Klarin D et al. “Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.” Nature Genetics 50(11):1514-1523 (2018)
Allele A
OR 0.28
p 3.0e-9
N 297,626
Major Consortium StudyLarge GWAS
multi-ancestry
Petty LE et al. “Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.” Nature Communications 16(1):3438 (2025)
Allele A
OR 0.12
p 6.0e-19
N 62,209
Large GWAS
Hispanic or Latin American

low density lipoprotein cholesterol measurement

Petty LE et al. “Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.” Nature Communications 16(1):3438 (2025)
Allele G
OR 0.28
p 5.0e-24
N 60,405
Large GWAS
Hispanic or Latin American
Hoffmann TJ et al. “A large electronic-health-record-based genome-wide study of serum lipids.” Nature Genetics 50(3):401-413 (2018)
Allele G
OR 0.26
p 5.0e-8
N 94,674
Large GWAS
multi-ancestry

high density lipoprotein cholesterol measurement

Kamiza AB et al. “Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry.” Nature Communications 14(1):5403 (2023)
Allele A
OR 0.03
p 3.0e-11
N 125,000
Large GWAS
African American or Afro-Caribbean, Sub-Saharan African, African unspecified

triglyceride measurement

Kamiza AB et al. “Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry.” Nature Communications 14(1):5403 (2023)
Allele A
OR 0.03
p 3.0e-10
N 125,000
Large GWAS
African American or Afro-Caribbean, Sub-Saharan African, African unspecified
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ClinVar annotation

Likely Benign★★★☆
17 submitters4 publications

Cardiovascular phenotype; Familial hypercholesterolemia; Hypercholesterolemia, autosomal dominant, 3 (FHCL3); Hypercholesterolemia, familial, 1; Hypobetalipoproteinemia; 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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