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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

PCSK9 Gene

protein-coding   GIFtS: 64
GCID: GC01P055505

Proprotein Convertase Subtilisin/Kexin Type 9

(Previous names: hypercholesterolemia, autosomal dominant 3)
(Previous symbol: HCHOLA3)
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for PCSK9 Gene:
This gene encodes a proprotein convertase belonging to the proteinase K subfamily of the secretory subtilase
family. The encoded protein is synthesized as a soluble zymogen that undergoes autocatalytic intramolecular
processing in the endoplasmic reticulum. The protein may function as a proprotein convertase. This protein plays
a role in cholesterol homeostasis and may have a role in the differentiation of cortical neurons. Mutations in
this gene have been associated with a third form of autosomal dominant familial hypercholesterolemia (HCHOLA3).
(provided by RefSeq, Jul 2008)

GeneCards Summary for PCSK9 Gene: 
PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein-coding gene. Diseases associated with PCSK9 include hypercholesterolemia, and hypercholesterolemia, familial, 3. 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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000001.10  NC_018912.2  NT_032977.9  
Regulatory elements:
   SABiosciences 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 SABiosciences Chromatin IP Primers for PCSK9

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

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
Subcellular location: 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 co-localizes 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
Sequence caution: Sequence=BAC11572.1; Type=Frameshift; Positions=494;
6/18 PDB 3D structures from and Proteopedia for PCSK9 (see all 18):
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:

  • UniProtKB: Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation
  • UniProtKB: 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
  • UniProtKB: Phosphorylation protects the propeptide against proteolysis
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q8NBP7

  • 4/33 DME Specific Peptides for PCSK9 (Q8NBP7) (see all 33)
     GWTLTGC  AHNAFGG  WRLPGTY  YSPASAP 

    PCSK9 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    PCSK9 Protein Expression
    REFSEQ proteins: NP_777596.2  
    ENSEMBL proteins: 
     ENSP00000303208   ENSP00000401598   ENSP00000441859  

    Human Recombinant Protein Products for PCSK9: 
    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for PCSK9 (Proprotein Convertase 9/PCSK9)
    Enzo Life Sciences proteins for PCSK9
    OriGene Purified Protein for PCSK9
    OriGene Protein Over-expression Lysate for PCSK9
    OriGene MassSpec for PCSK9 
    OriGene Custom Protein Services for PCSK9
    GenScript Custom Purified and Recombinant Proteins Services for PCSK9
    Novus Biologicals PCSK9 Lysate
    Sino Biological Recombinant Protein for PCSK9
    Sino Biological Cell Lysate for PCSK9 
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for PCSK9 

    Gene Ontology (GO): 5/12 cellular component terms (GO ID links to tree view) (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

    PCSK9 for ontologies           About GeneDecksing



    PCSK9 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of PCSK9
    R&D Systems Antibodies for PCSK9 (Proprotein Convertase 9/PCSK9)
    OriGene Antibodies for PCSK9
    OriGene Custom Antibody Services for PCSK9
    GenScript Custom Superior Antibodies Services for PCSK9
    Novus Biologicals PCSK9 Antibodies
    Abcam antibodies for PCSK9
    Cloud-Clone Corp. Antibodies for PCSK9 
    ThermoFisher Antibodies for PCSK9
    LSBio Antibodies in human, mouse, rat for PCSK9 

    Assay Products for PCSK9: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for PCSK9
    R&D Systems ELISAs for PCSK9 (Proprotein Convertase 9/PCSK9)         (see all)
    GenScript Custom Assay Services for PCSK9
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for PCSK9 
    Cloud-Clone Corp. CLIAs for PCSK9


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    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


    PCSK9 for domains           About GeneDecksing


    (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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    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): 5/11 molecular function terms (GO ID links to tree view) (see all 11):    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--
         
    PCSK9 for ontologies           About GeneDecksing


    Phenotypes:
         2 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Pcsk9):
     homeostasis/metabolism  liver/biliary system 

    PCSK9 for phenotypes           About GeneDecksing

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

       inGenious Targeting Laboratory - Custom generated mouse model solutions for PCSK9 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for PCSK9

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for PCSK9 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for PCSK9 

    miRNA
    Products:
        
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat PCSK9
    6 QIAGEN miScript miRNA 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
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for PCSK9
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat PCSK9

    Gene Editing
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    Sirion Biotech Customized adenovirus for overexpression of PCSK9

    Clone
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    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for PCSK9 (see all 7)
    OriGene ORF clones in mouse, rat for PCSK9
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: PCSK9 (NM_174936)
    Sino Biological Human cDNA Clone for PCSK9
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PCSK9
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PCSK9
    Sirion Biotech Customized lentivirus for stable overexpression of PCSK9 
                         Customized lentivirus expression plasmids for stable overexpression of PCSK9 

    Cell Line
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    GenScript Custom overexpressing Cell Line Services for PCSK9
    Search LifeMap BioReagents cell lines for PCSK9
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PCSK9


    (Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
    About This Section




    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for PCSK9

    STRING Interaction Network Preview (showing 5 interactants - click image to see 7)

    5/20 Interacting proteins for PCSK9 (Q8NBP72, 3 ENSP000003032084) via UniProtKB, MINT, STRING, and/or I2D (see all 20)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    LDLRP011303, ENSP000002524444I2D: score=1 STRING: ENSP00000252444
    ATAD2Q6PL183I2D: score=1 
    CAMK1DQ8IU853I2D: score=1 
    CDC34P494273I2D: score=1 
    DHPSP493663I2D: score=1 
    About this table

    Gene Ontology (GO): 5/26 biological process terms (GO ID links to tree view) (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--

    PCSK9 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    PCSK9 for compounds           About GeneDecksing

    EMD Millipore small molecules for PCSK9:
    Small Molecule - inhibitor
    Browse drugs & compounds from Enzo Life Sciences

    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)

    Search CenterWatch for drugs/clinical trials and news about PCSK9

    (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,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    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

    miRNA
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    6 QIAGEN miScript miRNA 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
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    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PCSK9
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PCSK9
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    Primer
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      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat PCSK9
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat PCSK9

    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 

    24/53 AceView cDNA sequences (see all 53):

    AI391587 AA552314 AA326415 AW003420 NM_174936 AI940122 AI694853 CB128618 
    BF000448 AI394000 H14619 BQ082431 AA588510 BQ082438 AK124635 BV176932 
    BX344968 BC042095 BQ428600 BM793806 AW014836 BE502330 AK075365 BX497762 

    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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    PCSK9 expression in normal human tissues (normalized intensities)      PCSK9 embryonic expression: see
    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 
     5/19 selected tissues (see all 19) fully expand
     
     Kidney (Urinary System)    fully expand to see all 10 entries
             Distal Renal Vesicle Cells Renal Vesicle
             Metanephros
             visceral organ/mesonephros/nephric duct, mesonephric portion   
     
     Brain (Nervous System)    fully expand to see all 7 entries
             Pons
             Olfactory Bulb   
     
     Eye (Sensory Organs)    fully expand to see all 3 entries
             Glycinergic Amacrine Cells Inner Nuclear Layer
             Human Keratocyte (HK)   
     
     Fibroblast
             Human Lymphatic Fibroblasts (HLF)   
     
     Gut Tube (Gastrointestinal Tract)    fully expand to see all 2 entries
             Hindgut

    See PCSK9 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for PCSK9

    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

        SABiosciences Expression via Pathway-Focused 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)
    About This Section

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

    Orthologs for PCSK9 gene from 5/11 species (see all 11)    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 80.69(n)1
    77.44(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 68.84(n)
    62.86(a)
      424664  XM_003641691.1  XP_003641739.1 
    lizard
    (Anolis carolinensis)
    Reptilia PCSK96
    Uncharacterized protein
    61(a)
    1 ↔ 1
    4(104277264-104302469)
    zebrafish
    (Danio rerio)
    Actinopterygii pcsk91 proprotein convertase subtilisin/kexin type 9 59.05(n)
    54.59(a)
      100150316  XM_003200677.1  XP_003200725.1 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes YSP3(YOR003W)4 Putative precursor to the subtilisin-like protease more   --   15(331455-332891) 854164  NP_014645.1 


    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)
    About This Section
      --

    (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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    UniProtKB/Swiss-Prot: PCSK9_HUMAN, Q8NBP7
    Polymorphism: Variant Leu-23 ins polymorphism in PCSK9 might have a modifier effect on LDLR mutation and familial
    hypercholesterolemia
    Polymorphism: Genetic variations in PCSK9 define the low density lipoprotein cholesterol level quantitative trait
    locus 1 (LDLCQ1) [MIM:603776]


    10/877 SNPs in PCSK9 are shown (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) 10/11 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
    SABiosciences Cancer Mutation PCR Assays
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    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, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    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

  • 20/32 diseases for PCSK9 (see all 32):    About MalaCards
    hypercholesterolemia    hypercholesterolemia, familial, 3    familial hypercholesterolemia, autosomal dominant, 3    hypercholesterolemia, autosomal dominant
    familial hypercholesterolemia    familial hyperlipidemia    hypobetalipoproteinemia    abetalipoproteinemia
    ischemic heart disease    gigantism    coronary heart disease    acne
    fatty liver disease    narcolepsy    atherosclerosis    vascular disease
    liver disease    wilms tumor    dementia    kidney disease

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

    PCSK9 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    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)
    About This Section

    PubMed articles for PCSK9 gene, integrated from 9 sources (see all 290):
    (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. (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. (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. (2009)
    4. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. (PubMed id 12730697)1, 2, 3, 9 Abifadel M.... Boileau C. (2003)
    5. Self-association of human PCSK9 correlates with its LDLR-degrading activity. (PubMed id 18197702)1, 2, 9 Fan D....Fazio S. (2008)
    6. The E32K variant of PCSK9 exacerbates the phenotype o f familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation. (PubMed id 20006333)1, 4, 9 Noguchi T....Mabuchi H. (2010)
    7. Healthy individuals carrying the PCSK9 p.R46L variant and familial hypercholesterolemia patients carrying PCSK9 p.D374Y exhibit lowe r plasma concentrations of PCSK9. (PubMed id 19797716)1, 4, 9 Humphries S.E....Neil A. (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. (2007)
    9. Molecular basis of PCSK9 function. (PubMed id 18649882)1, 2, 9 Lambert G....Piper D.E. (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. (2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     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)
    About This Section
    Entrez Gene: 255738 HGNC: 20001 AceView: PCSK9 Ensembl:ENSG00000169174 euGenes: HUgn255738
    ECgene: PCSK9 H-InvDB: PCSK9

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    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.)
    About This Section
    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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