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PCSK9 Gene

protein-coding   GIFtS: 65
GCID: GC01P055505

Proprotein Convertase Subtilisin/Kexin Type 9

(Previous names: hypercholesterolemia, autosomal dominant 3)
(Previous symbol: HCHOLA3)
  See PCSK9-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Proprotein Convertase Subtilisin/Kexin Type 91 2     Hypercholesterolemia, Autosomal Dominant 31
HCHOLA31 2 5     Convertase Subtilisin/Kexin Type 9 Preproprotein2
NARC12 3 5     Neural Apoptosis Regulated Convertase 12
Subtilisin/Kexin-Like Protease PC92 3     EC 3.4.21.-3
NARC-12 3     Neural Apoptosis-Regulated Convertase 13
PC92 3     Proprotein Convertase 93
FH32 5     EC 3.4.218
LDLCQ12 5     EC 3.4.21.1118

External Ids:    HGNC: 200011   Entrez Gene: 2557382   Ensembl: ENSG000001691747   OMIM: 6077865   UniProtKB: Q8NBP73   

Export aliases for PCSK9 gene to outside databases

Previous GC identifers: GC01P054862 GC01P054875 GC01P055217 GC01P055277 GC01P053618


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 low density lipoprotein cholesterol level qtl 1, and pcsk9-related familial hypercholesterolemia, autosomal dominant. GO annotations related to this gene include protein self-association and identical protein binding.

UniProtKB/Swiss-Prot: PCSK9_HUMAN, Q8NBP7
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

Gene Wiki entry for PCSK9 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000001.10  NC_018912.2  NT_032977.10  
Regulatory elements:
   Regulatory transcription factor binding sites in the PCSK9 gene promoter:
         RFX1   HOXA3   NCX/Ncx   HNF-3beta   Cdc5   HNF-1A   PPAR-alpha   HNF-1   ZID   Msx-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidPCSK9 promoter sequence
   Search Chromatin IP Primers for PCSK9

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat PCSK9


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1p32.3   Ensembl cytogenetic band:  1p32.3   HGNC cytogenetic band: 1p34.1-p32

PCSK9 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PCSK9 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01P055505:  view genomic region     (about GC identifiers)

Start:
55,505,149 bp from pter      End:
55,530,526 bp from pter
Size:
25,378 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: PCSK9_HUMAN, Q8NBP7 (See protein sequence)
Recommended Name: Proprotein convertase subtilisin/kexin type 9 precursor  
Size: 692 amino acids; 74286 Da
Cofactor: Calcium (Probable)
Subunit: 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
Sequence caution: Sequence=BAC11572.1; Type=Frameshift; Positions=494;
Selected PDB 3D structures from and Proteopedia for PCSK9 (see all 19):
2P4E (3D)        2PMW (3D)        2QTW (3D)        2W2M (3D)        2W2N (3D)        2W2O (3D)    
Secondary accessions: A8T640 C0JYY9 Q5PSM5 Q5SZQ2
Alternative splicing: 2 isoforms:  Q8NBP7-1   Q8NBP7-2   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for PCSK9: NX_Q8NBP7

Explore proteomics data for PCSK9 at MOPED

Post-translational modifications: 

  • Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation1
  • 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 protein1
  • Phosphorylation protects the propeptide against proteolysis1
  • Glycosylation2 at Asn533
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for PCSK9 (Q8NBP7) (see all 33)
     GWTLTGC  AHNAFGG  WRLPGTY  YSPASAP 


    See PCSK9 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_777596.2  
    ENSEMBL proteins: 
     ENSP00000303208   ENSP00000401598   ENSP00000441859  

    PCSK9 Human Recombinant Protein Products:

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    Cloud-Clone Corp. Proteins for PCSK9

     
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    Search eBioscience for ELISAs for PCSK9 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    4 InterPro protein domains:
     IPR000209 Peptidase_S8/S53_dom
     IPR015500 Peptidase_S8_subtilisin-rel
     IPR010259 Inhibitor_I9
     IPR009020 Prot_inh_propept

    Graphical View of Domain Structure for InterPro Entry Q8NBP7

    ProtoNet protein and cluster: Q8NBP7

    1 Blocks protein domain: IPB000209 Subtilisin serine protease family (S8) signature

    UniProtKB/Swiss-Prot: PCSK9_HUMAN, Q8NBP7
    Domain: The C-terminal domain (CRD) is essential for the LDLR-binding and degrading activities (PubMed:22027821)
    Domain: The catalytic domain is responsible for mediating its self-association
    Similarity: Belongs to the peptidase S8 family
    Similarity: Contains 1 peptidase S8 domain


    Find genes that share domains with PCSK9           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: PCSK9_HUMAN, Q8NBP7
    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 regulation: Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the
    catalytic domain. Inhibited by EGTA

         Enzyme Numbers (IUBMB): EC 3.4.212 EC 3.4.21.1112 EC 3.4.21.-1

         Gene Ontology (GO): Selected molecular function terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004252serine-type endopeptidase activity IDA12552133
    GO:0005515protein binding IPI17461796
    GO:0019871sodium channel inhibitor activity IDA--
    GO:0030169low-density lipoprotein particle binding ISS--
    GO:0034185apolipoprotein binding ISS--
         
    Find genes that share ontologies with PCSK9           About GenesLikeMe


    Phenotypes:
         2 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Pcsk9):
     homeostasis/metabolism  liver/biliary system 

    Find genes that share phenotypes with PCSK9           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for PCSK9: Pcsk9tm1Jdh Pcsk9tm1.2Prat

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for PCSK9
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       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for PCSK9

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    Block miRNA regulation of human, mouse, rat PCSK9 using miScript Target Protectors
    6 qRT-PCR Assays for microRNAs that regulate PCSK9:
    hsa-miR-224 hsa-miR-187* hsa-miR-1283 hsa-miR-520d-5p hsa-miR-524-5p hsa-miR-1912
    SwitchGear 3'UTR luciferase reporter plasmidPCSK9 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    PCSK9_HUMAN, Q8NBP7: 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: 

    CompartmentConfidence
    endoplasmic reticulum5
    endosome5
    extracellular5
    golgi apparatus5
    lysosome5
    vacuole5
    plasma membrane3
    cytoskeleton1
    nucleus1

    Gene Ontology (GO): Selected cellular component terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region ----
    GO:0005615extracellular space IDA12552133
    GO:0005737cytoplasm IDA--
    GO:0005764lysosome IDA17461796
    GO:0005769early endosome IDA17461796

    Find genes that share ontologies with PCSK9           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Pathway & Disease-focused RT2 Profiler PCR Array including PCSK9: 
              Lipoprotein Signaling & Cholesterol Metabolism in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for PCSK9

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for PCSK9 (Q8NBP71, 2, 3 ENSP000003032084) via UniProtKB, MINT, STRING, and/or I2D (see all 42)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    LDLRP011301, 3, ENSP000002524444EBI-7539251,EBI-988319 I2D: score=1 STRING: ENSP00000252444
    TREHO432803, ENSP000002640294I2D: score=1 STRING: ENSP00000264029
    ATAD2Q6PL183I2D: score=1 
    CAMK1DQ8IU853I2D: score=1 
    CDC34P494273I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 26):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001822kidney development ISS12552133
    GO:0001889liver development ISS12552133
    GO:0001920negative regulation of receptor recycling IDA17452316
    GO:0002092positive regulation of receptor internalization IDA17328821
    GO:0006508proteolysis IBA--

    Find genes that share ontologies with PCSK9           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for PCSK9

    1 HMDB Compound for PCSK9    About this table
    CompoundSynonyms CAS #PubMed Ids
    CalciumCa (see all 2)7440-70-2--

    6 Novoseek inferred chemical compound relationships for PCSK9 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cholesterol 74.2 172 17170371 (5), 18695239 (4), 18666258 (4), 20333646 (4) (see all 70)
    sterol 46.5 11 15772090 (1), 15677715 (1), 20048381 (1), 17448444 (1) (see all 6)
    serine 34.1 13 17051583 (2), 18300938 (1), 15677715 (1), 17608623 (1) (see all 10)
    lipid 26.6 9 17550346 (3), 18666258 (1), 18710658 (1), 20048381 (1) (see all 7)
    oligonucleotide 6.75 4 20498851 (2), 16465619 (1), 17242417 (1)
    hydrogen 0 3 19224862 (1)

    1 PharmGKB related drug/compound annotation for PCSK9 gene    About this table
    Drug/compound PharmGKB Annotation
    lomitapide



    Find genes that share compounds with PCSK9           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for PCSK9 gene: 
    NM_174936.3  

    Unigene Cluster for PCSK9:

    Proprotein convertase subtilisin/kexin type 9
    Hs.18844  [show with all ESTs]
    Unigene Representative Sequence: AK124635
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000302118(uc001cyf.2 uc010oom.2) ENST00000490692 ENST00000452118(uc010ool.2)
    ENST00000543384
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    Additional mRNA sequence: 

    AK075365.1 AK122717.1 AK124635.1 BC042095.1 

    6 DOTS entries:

    DT.410715  DT.101961321  DT.100651497  DT.100706630  DT.100835112  DT.97834339 

    Selected AceView cDNA sequences (see all 53):

    BF000448 NM_174936 AA326415 AI391587 AA552314 AI394000 AW003420 AI940122 
    H14619 AI694853 CB128618 BE502330 BF063012 BU621267 AK075365 AK122717 
    BX497762 BQ428600 AA233897 BC042095 BX344968 AI625123 AA588510 BX497763 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for PCSK9    About this scheme

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


    ECgene alternative splicing isoforms for PCSK9

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    PCSK9 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GTCGGGGGAG
    PCSK9 Expression
    About this image


    PCSK9 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 10) fully expand
     
     Kidney (Urinary System)    fully expand to see all 8 entries
             Distal Renal Vesicle Cells Renal Vesicle
             Metanephros
     
     Gut Tube (Gastrointestinal Tract)    fully expand to see all 2 entries
             Hindgut
     
     Eye (Sensory Organs)    fully expand to see all 2 entries
             GABAergic Amacrine Cells Inner Nuclear Layer
     
     Neurons
             GABAergic Amacrine Cells Inner Nuclear Layer
     
     Liver (Hepatobiliary System)
             Liver Lobule
    PCSK9 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    PCSK9 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.18844

    UniProtKB/Swiss-Prot: PCSK9_HUMAN, Q8NBP7
    Tissue specificity: Expressed in neuro-epithelioma, colon carcinoma, hepatic and pancreatic cell lines, and in
    Schwann cells

        Pathway & Disease-focused RT2 Profiler PCR Array including PCSK9: 
              Lipoprotein Signaling & Cholesterol Metabolism in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for PCSK9 gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Pcsk91 , 5 proprotein convertase subtilisin/kexin type 91, 5 80.84(n)1
    77.83(a)1
      4 (49.67 cM)5
    1001021  NM_153565.21  NP_705793.11 
     1064423295 
    chicken
    (Gallus gallus)
    Aves PCSK91 proprotein convertase subtilisin/kexin type 9 68.98(n)
    64.3(a)
      424664  XM_003641691.2  XP_003641739.2 
    lizard
    (Anolis carolinensis)
    Reptilia PCSK96
    proprotein convertase subtilisin/kexin type 9
    61(a)
    1 ↔ 1
    4(104277264-104302469)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia pcsk91 proprotein convertase subtilisin/kexin type 9 62.57(n)
    61.9(a)
      100484989  XM_002931433.2  XP_002931479.1 
    zebrafish
    (Danio rerio)
    Actinopterygii pcsk91 proprotein convertase subtilisin/kexin type 9 59.57(n)
    55.52(a)
      100150316  XM_003200677.2  XP_003200725.1 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes YSP3(YOR003W)4
    YSP31
    Putative precursor to the subtilisin-like protease more4
    YSP31
    42.52(n)1
    34.6(a)1
      15(331455-332891)4
    8541641, 4  NP_014645.11, 4 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    PCSK9_HUMAN, Q8NBP7: Variant Leu-23 ins polymorphism in PCSK9 might have a modifier effect on LDLR mutation and familial
    hypercholesterolemia
    PCSK9_HUMAN, Q8NBP7: Genetic variations in PCSK9 define the low density lipoprotein cholesterol level quantitative trait
    locus 1 (LDLCQ1) [MIM:603776]


    Selected SNPs for PCSK9 (see all 877)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0585264
    Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)4--see VAR_0585262 R H mis40--------
    VAR_0585314
    Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)4--see VAR_0585312 D H mis40--------
    VAR_0585304
    Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)4--see VAR_0585302 R H mis40--------
    VAR_0585244
    Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)4--see VAR_0585242 D G mis40--------
    VAR_0585344
    Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)4--see VAR_0585342 R W mis40--------
    VAR_0585324
    Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)4--see VAR_0585322 D Y mis40--------
    VAR_0585274
    Hypercholesterolemia, autosomal dominant, 3 (HCHOLA3)4--see VAR_0585272 R S mis40--------
    rs454480951,2
    C,Fnon-pathogenic155581846(+) GCCGCC/TGGCGT 1 -- ut516Minor allele frequency- T:0.11NS NA EA 1068
    rs115836801,2,,4
    C,F,Hnon-pathogenic155582067(+) CCTGGC/TCGAAG 2 A V mis1 ese319Minor allele frequency- T:0.09NS EA NA 6330
    rs118002311,2
    C,F,Hnon-pathogenic155594337(+) ATGTCA/G/TCCTTG 1 -- int115NA EA NS WA CSA EU 2860

    HapMap Linkage Disequilibrium report for PCSK9 (55505149 - 55530526 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for PCSK9 (see all 11):    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv527707CNV Loss19592680
    nsv518638CNV Loss19592680
    nsv517995CNV Loss19592680
    nsv527129CNV Loss19592680
    nsv871653CNV Loss21882294
    nsv518539CNV Loss19592680
    nsv870896CNV Gain21882294
    nsv870795CNV Gain21882294
    nsv817614CNV Gain22305530
    dgv230n71CNV Gain21882294

    Human Gene Mutation Database (HGMD): PCSK9
    Locus Specific Mutation Databases (LSDB): PCSK9

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing PCSK9
    DNA2.0 Custom Variant and Variant Library Synthesis for PCSK9

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 607786   
    OMIM disorders: 603776  
    UniProtKB/Swiss-Prot: PCSK9_HUMAN, Q8NBP7
  • 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. Note=The disease is caused by mutations affecting the gene represented in this entry

  • 7 diseases for PCSK9:    
    About MalaCards
    low density lipoprotein cholesterol level qtl 1    pcsk9-related familial hypercholesterolemia, autosomal dominant    hypercholesterolemia, familial, 3    hypobetalipoproteinemia, familial, 2
    hypercholesterolemia    familial hypercholesterolemia    familial hyperlipidemia

    6 diseases from the University of Copenhagen DISEASES database for PCSK9:
    Lung cancer     Familial hyperlipidemia     Coronary heart disease     Hypobetalipoproteinemia
    Abetalipoproteinemia     Atherosclerosis

    Find genes that share disorders with PCSK9           About GenesLikeMe

    8 Novoseek inferred disease relationships for PCSK9 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    hypercholesterolemia, autosomal dominant 96.8 30 15099351 (3), 15767856 (3), 16211558 (1), 18710658 (1) (see all 20)
    hypercholesterolemia familial 90.5 37 19797716 (2), 19319977 (2), 17765244 (2), 19917273 (2) (see all 23)
    hypocholesterolemia 86 19 16424354 (2), 18710658 (2), 17493938 (2), 17495605 (1) (see all 12)
    hypercholesterolemia 76.6 52 18266662 (3), 19191301 (2), 18354137 (2), 15166014 (2) (see all 27)
    hypercholesterolemia, autosomal recessive 73.3 2 17449864 (1), 17080197 (1)
    coronary heart disease 64.4 26 19075777 (2), 19020338 (1), 17964958 (1), 18300938 (1) (see all 22)
    atherosclerosis 42.7 11 16554528 (1), 17804797 (1), 17940607 (1), 18631360 (1) (see all 8)
    cardiovascular diseases 31.1 5 19265033 (2), 17435765 (1), 18262190 (1)

    Genetic Association Database (GAD): PCSK9
    Human Genome Epidemiology (HuGE) Navigator: PCSK9 (71 documents)

    Export disorders for PCSK9 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for PCSK9 gene, integrated from 10 sources (see all 312):
    (articles sorted by number of sources associating them with PCSK9)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. (PubMed id 12552133)1, 2, 3, 9 Seidah N.G.... Chretien M. (Proc. Natl. Acad. Sci. U.S.A. 2003)
    2. A spectrum of PCSK9 alleles contributes to plasma levels of low- density lipoprotein cholesterol. (PubMed id 16465619)1, 2, 4, 9 Kotowski I.K.... Hobbs H.H. (Am. J. Hum. Genet. 2006)
    3. The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene. (PubMed id 19319977)1, 2, 4, 9 Abifadel M.... Boileau C. (Hum. Mutat. 2009)
    4. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. (PubMed id 12730697)1, 2, 3, 9 Abifadel M.... Boileau C. (Nat. Genet. 2003)
    5. Self-association of human PCSK9 correlates with its LDLR-degrading activity. (PubMed id 18197702)1, 2, 9 Fan D....Fazio S. (Biochemistry 2008)
    6. The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation. (PubMed id 20006333)1, 4, 9 Noguchi T....Mabuchi H. (Atherosclerosis 2010)
    7. Healthy individuals carrying the PCSK9 p.R46L variant and familial hypercholesterolemia patients carrying PCSK9 p.D374Y exhibit lower plasma concentrations of PCSK9. (PubMed id 19797716)1, 4, 9 Humphries S.E....Neil A. (Clin. Chem. 2009)
    8. The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. (PubMed id 17461796)1, 2, 9 Nassoury N.... Seidah N.G. (Traffic 2007)
    9. Molecular basis of PCSK9 function. (PubMed id 18649882)1, 2, 9 Lambert G.... Piper D.E. (Atherosclerosis 2009)
    10. The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. (PubMed id 18039658)1, 2, 9 Poirier S.... Seidah N.G. (J. Biol. Chem. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 255738 HGNC: 20001 AceView: PCSK9 Ensembl:ENSG00000169174 euGenes: HUgn255738
    ECgene: PCSK9 H-InvDB: PCSK9

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for PCSK9 Pharmacogenomics, SNPs, Pathways
    SeattleSNPshttp://pga.gs.washington.edu/data/pcsk9/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for PCSK9 gene:
    Search GeneIP for patents involving PCSK9

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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