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PCSK9

Chr 1p32.3

proprotein convertase subtilisin/kexin type 9

Aliases:
NARC-1, FH3
MANE:
ENST00000302118.5
OMIM: 607786 ↗NCBI: 255738 ↗Ensembl ↗

Annotations refreshed 8 hours ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • Additional findings health related

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

  • Additional findings health related - children

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

  • Familial hypercholesterolaemia

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

  • Familial hypercholesterolaemia (GMS)

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

  • Likely inborn error of metabolism

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

  • Undiagnosed metabolic disorders

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

  • Childhood onset dystonia, chorea or related movement disorder

Disease associations (Open Targets)

  • familial hypercholesterolemia

    0.85

  • Hypercholesterolemia

    0.82

  • hypercholesterolemia, autosomal dominant, 3

    0.82

  • cardiovascular disorder

    0.72

  • coronary artery disorder

    0.72

  • metabolic disease

    0.71

  • hyperlipidemia

    0.66

  • myocardial infarction

    0.65

  • homozygous familial hypercholesterolemia

    0.65

  • Disorder of lipid metabolism

    0.65

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Proprotein convertase subtilisin/kexin type 9

Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments (PubMed:18039658). Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation (PubMed:17461796, PubMed:18197702, PubMed:18799458, PubMed:22074827). Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway (PubMed:18660751). Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways

Diseases associated with PCSK9

Curated MONDO disease pages that list PCSK9 among their top associated genes.

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.