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Aliases for PCSK9 Gene

Aliases for PCSK9 Gene

  • Proprotein Convertase Subtilisin/Kexin Type 9 2 3
  • NARC1 3 4 6
  • Subtilisin/Kexin-Like Protease PC9 3 4
  • HCHOLA3 3 6
  • LDLCQ1 3 6
  • NARC-1 3 4
  • FH3 3 6
  • PC9 3 4
  • Convertase Subtilisin/Kexin Type 9 Preproprotein 3
  • Hypercholesterolemia, Autosomal Dominant 3 2
  • Neural Apoptosis Regulated Convertase 1 3
  • Neural Apoptosis-Regulated Convertase 1 4
  • Proprotein Convertase 9 4
  • EC 3.4.21.111 63
  • EC 3.4.21.- 4
  • EC 3.4.21 63

External Ids for PCSK9 Gene

Previous HGNC Symbols for PCSK9 Gene

  • HCHOLA3

Previous GeneCards Identifiers for PCSK9 Gene

  • GC01P054862
  • GC01P054875
  • GC01P055217
  • GC01P055277
  • GC01P055505
  • GC01P053618

Summaries for PCSK9 Gene

Entrez Gene Summary for PCSK9 Gene

  • 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]

GeneCards Summary for PCSK9 Gene

PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) is a Protein Coding gene. Diseases associated with PCSK9 include hypercholesterolemia, familial, 3 and pcsk9-related familial hypercholesterolemia, autosomal dominant. GO annotations related to this gene include identical protein binding and protein self-association.

UniProtKB/Swiss-Prot for PCSK9 Gene

  • 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. 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. 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. 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.

Gene Wiki entry for PCSK9 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PCSK9 Gene

Genomics for PCSK9 Gene

Regulatory Elements for PCSK9 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for PCSK9 Gene

Start:
55,039,476 bp from pter
End:
55,064,853 bp from pter
Size:
25,378 bases
Orientation:
Plus strand

Genomic View for PCSK9 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PCSK9 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PCSK9 Gene

Proteins for PCSK9 Gene

  • Protein details for PCSK9 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8NBP7-PCSK9_HUMAN
    Recommended name:
    Proprotein convertase subtilisin/kexin type 9
    Protein Accession:
    Q8NBP7
    Secondary Accessions:
    • A8T640
    • C0JYY9
    • Q5PSM5
    • Q5SZQ2

    Protein attributes for PCSK9 Gene

    Size:
    692 amino acids
    Molecular mass:
    74286 Da
    Cofactor:
    Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
    Quaternary structure:
    • Monomer. Can self-associate to form dimers and higher multimers which may have increased LDLR degrading activity. The precursor protein but not the mature protein may form multimers. Interacts with APOB, VLDLR, LRP8/APOER2 and BACE1. The full length immature form (pro-PCSK9) interacts with SCNN1A, SCNN1B and SCNN1G. The pro-PCSK9 form (via C-terminal domain) interacts with LDLR.
    SequenceCaution:
    • Sequence=BAC11572.1; Type=Frameshift; Positions=494; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for PCSK9 Gene

    Alternative splice isoforms for PCSK9 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PCSK9 Gene

Proteomics data for PCSK9 Gene at MOPED

Post-translational modifications for PCSK9 Gene

  • Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation
  • Phosphorylation protects the propeptide against proteolysis.
  • Undergoes autocatalytic cleavage in the endoplasmic reticulum to release the propeptide from the N-terminus and the cleavage of the propeptide is strictly required for its maturation and activation. The cleaved propeptide however remains associated with the catalytic domain through non-covalent interactions, preventing potential substrates from accessing its active site. As a result, it is secreted from cells as a propeptide-containing, enzymatically inactive protein.
  • Glycosylation at Asn533
  • Modification sites at PhosphoSitePlus

Other Protein References for PCSK9 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for PCSK9 (Proprotein Convertase 9/PCSK9)

Protein Products

  • Novus Biologicals lysates for PCSK9

Domains for PCSK9 Gene

Graphical View of Domain Structure for InterPro Entry

Q8NBP7

UniProtKB/Swiss-Prot:

PCSK9_HUMAN :
  • Q8NBP7
Domain:
  • The C-terminal domain (CRD) is essential for the LDLR-binding and degrading activities.
  • The catalytic domain is responsible for mediating its self-association.
  • Contains 1 peptidase S8 domain.
Family:
  • Belongs to the peptidase S8 family.
genes like me logo Genes that share domains with PCSK9: view

No data available for Gene Families for PCSK9 Gene

Function for PCSK9 Gene

Molecular function for PCSK9 Gene

UniProtKB/Swiss-Prot EnzymeRegulation: Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA
UniProtKB/Swiss-Prot Function: 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. 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. 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. 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.

Enzyme Numbers (IUBMB) for PCSK9 Gene

Gene Ontology (GO) - Molecular Function for PCSK9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IDA 12552133
GO:0005515 protein binding IPI 17461796
GO:0019871 sodium channel inhibitor activity IDA 22493497
GO:0030169 low-density lipoprotein particle binding ISS --
GO:0030547 receptor inhibitor activity IDA 22848640
genes like me logo Genes that share ontologies with PCSK9: view

Phenotypes for PCSK9 Gene

genes like me logo Genes that share phenotypes with PCSK9: view

Animal Models for PCSK9 Gene

MGI Knock Outs for PCSK9:

Animal Model Products

CRISPR Products

miRNA for PCSK9 Gene

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PCSK9

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targeting and HOMER Transcription for PCSK9 Gene

Localization for PCSK9 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PCSK9 Gene

Cytoplasm. Secreted. Endosome. Lysosome. Cell surface. Endoplasmic reticulum. Golgi apparatus. Note=Autocatalytic cleavage is required to transport it from the endoplasmic reticulum to the Golgi apparatus and for the secretion of the mature protein. Localizes to the endoplasmic reticulum in the absence of LDLR and colocalizes to the cell surface and to the endosomes/lysosomes in the presence of LDLR. The sorting to the cell surface and endosomes is required in order to fully promote LDLR degradation.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PCSK9 Gene COMPARTMENTS Subcellular localization image for PCSK9 gene
Compartment Confidence
endoplasmic reticulum 5
endosome 5
extracellular 5
golgi apparatus 5
lysosome 5
vacuole 5
plasma membrane 3
cytoskeleton 1
nucleus 1

Gene Ontology (GO) - Cellular Components for PCSK9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region --
GO:0005615 extracellular space IDA 12552133
GO:0005737 cytoplasm IDA 22580899
GO:0005764 lysosome IDA 17461796
GO:0005769 early endosome IDA 17461796
genes like me logo Genes that share ontologies with PCSK9: view

Pathways for PCSK9 Gene

SuperPathways for PCSK9 Gene

No Data Available

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays
    • Lipoprotein Signaling & Cholesterol Metabolism in human,mouse,rat

Gene Ontology (GO) - Biological Process for PCSK9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001822 kidney development ISS 12552133
GO:0001889 liver development ISS 12552133
GO:0001920 negative regulation of receptor recycling IDA 17452316
GO:0002092 positive regulation of receptor internalization IDA 17328821
GO:0006508 proteolysis IBA --
genes like me logo Genes that share ontologies with PCSK9: view

No data available for Pathways by source for PCSK9 Gene

Compounds for PCSK9 Gene

(1) HMDB Compounds for PCSK9 Gene

Compound Synonyms Cas Number PubMed IDs
Calcium
  • Ca
7440-70-2

(6) Novoseek inferred chemical compound relationships for PCSK9 Gene

Compound -log(P) Hits PubMed IDs
cholesterol 74.2 128
sterol 46.5 6
serine 34.1 11
lipid 26.6 9
oligonucleotide 6.75 4

(1) PharmGKB related drug/compound annotations for PCSK9 Gene

Drug/compound Annotation
lomitapide
genes like me logo Genes that share compounds with PCSK9: view

Transcripts for PCSK9 Gene

mRNA/cDNA for PCSK9 Gene

Unigene Clusters for PCSK9 Gene

Proprotein convertase subtilisin/kexin type 9:
Representative Sequences:

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PCSK9

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for PCSK9

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for PCSK9 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13 ^ 14
SP1: - - - -
SP2: - -
SP3: -
SP4: - -

Relevant External Links for PCSK9 Gene

GeneLoc Exon Structure for
PCSK9
ECgene alternative splicing isoforms for
PCSK9

Expression for PCSK9 Gene

mRNA expression in normal human tissues for PCSK9 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PCSK9 Gene

This gene is overexpressed in Liver (18.8), Brain - Cerebellar Hemisphere (6.1), and Brain - Cerebellum (5.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for PCSK9 Gene

SOURCE GeneReport for Unigene cluster for PCSK9 Gene Hs.18844

mRNA Expression by UniProt/SwissProt for PCSK9 Gene

Q8NBP7-PCSK9_HUMAN
Tissue specificity: Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in Schwann cells
genes like me logo Genes that share expressions with PCSK9: view

In Situ Assay Products

Orthologs for PCSK9 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PCSK9 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PCSK9 35
  • 99.13 (n)
  • 98.99 (a)
PCSK9 36
  • 99 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PCSK9 36
  • 79 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Pcsk9 35
  • 80.84 (n)
  • 77.83 (a)
Pcsk9 16
Pcsk9 36
  • 77 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia PCSK9 36
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PCSK9 36
  • 43 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Pcsk9 35
  • 81 (n)
  • 78.13 (a)
chicken
(Gallus gallus)
Aves PCSK9 35
  • 68.98 (n)
  • 64.3 (a)
PCSK9 36
  • 64 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PCSK9 36
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia pcsk9 35
  • 62.57 (n)
  • 61.9 (a)
zebrafish
(Danio rerio)
Actinopterygii pcsk9 35
  • 59.57 (n)
  • 55.52 (a)
pcsk9 36
  • 52 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PRB1 36
  • 20 (a)
OneToMany
RRT12 36
  • 26 (a)
OneToMany
YSP3 35
  • 42.52 (n)
  • 34.6 (a)
YSP3 36
  • 24 (a)
OneToMany
YSP3 38
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes psp3 35
  • 45.03 (n)
  • 34.8 (a)
Species with no ortholog for PCSK9:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • cow (Bos Taurus)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PCSK9 Gene

ENSEMBL:
Gene Tree for PCSK9 (if available)
TreeFam:
Gene Tree for PCSK9 (if available)

Paralogs for PCSK9 Gene

No data available for Paralogs for PCSK9 Gene

Variants for PCSK9 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for PCSK9 Gene

Q8NBP7-PCSK9_HUMAN
Genetic variations in PCSK9 define the low density lipoprotein cholesterol level quantitative trait locus 1 (LDLCQ1) [MIM:603776]

Sequence variations from dbSNP and Humsavar for PCSK9 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs471705 -- 55,055,569(+) TAGGA(G/T)GTATA intron-variant
rs472495 -- 55,055,640(+) GGCCA(G/T)GCAGG intron-variant
rs479832 -- 55,049,864(+) CCCCA(C/T)AGTGG intron-variant
rs479910 -- 55,056,468(+) CCCAC(A/G)CCCCG intron-variant
rs483462 -- 55,059,727(+) TGCCC(A/G)CGAGG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for PCSK9 Gene

Variant ID Type Subtype PubMed ID
nsv817614 CNV Gain 22305530
nsv527129 CNV Loss 19592680
nsv518539 CNV Loss 19592680
nsv871300 CNV Gain 21882294
nsv870795 CNV Gain 21882294
nsv870896 CNV Gain 21882294
nsv518638 CNV Loss 19592680
nsv527707 CNV Loss 19592680
dgv230n71 CNV Gain 21882294
nsv871653 CNV Loss 21882294
nsv517995 CNV Loss 19592680

Relevant External Links for PCSK9 Gene

HapMap Linkage Disequilibrium report
PCSK9
Human Gene Mutation Database (HGMD)
PCSK9
Locus Specific Mutation Databases (LSDB)
PCSK9

Disorders for PCSK9 Gene

(1) OMIM Diseases for PCSK9 Gene (607786)

UniProtKB/Swiss-Prot

PCSK9_HUMAN
  • Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3) [MIM:603776]: A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins. {ECO:0000269 PubMed:12730697}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(8) Novoseek inferred disease relationships for PCSK9 Gene

Disease -log(P) Hits PubMed IDs
hypercholesterolemia, autosomal dominant 96.8 24
hypercholesterolemia familial 90.5 27
hypocholesterolemia 86 15
hypercholesterolemia 76.6 36
hypercholesterolemia, autosomal recessive 73.3 2

Relevant External Links for PCSK9

Genetic Association Database (GAD)
PCSK9
Human Genome Epidemiology (HuGE) Navigator
PCSK9
genes like me logo Genes that share disorders with PCSK9: view

Publications for PCSK9 Gene

  1. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. (PMID: 12552133) Seidah N.G. … Chretien M. (Proc. Natl. Acad. Sci. U.S.A. 2003) 2 3 4 23
  2. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. (PMID: 12730697) Abifadel M. … Boileau C. (Nat. Genet. 2003) 2 3 4 23
  3. A spectrum of PCSK9 alleles contributes to plasma levels of low- density lipoprotein cholesterol. (PMID: 16465619) Kotowski I.K. … Hobbs H.H. (Am. J. Hum. Genet. 2006) 3 4 23 48
  4. The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene. (PMID: 19319977) Abifadel M. … Boileau C. (Hum. Mutat. 2009) 3 4 23 48
  5. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. (PMID: 19191301) Abifadel M. … Boileau C. (Hum. Mutat. 2009) 3 4 23

Products for PCSK9 Gene

  • Addgene plasmids for PCSK9

Sources for PCSK9 Gene

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