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    PCSK9 proprotein convertase subtilisin/kexin type 9 [ Homo sapiens (human) ]

    Gene ID: 255738, updated on 26-Jul-2021

    Summary

    Official Symbol
    PCSK9provided by HGNC
    Official Full Name
    proprotein convertase subtilisin/kexin type 9provided by HGNC
    Primary source
    HGNC:HGNC:20001
    See related
    Ensembl:ENSG00000169174 MIM:607786
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FH3; PC9; FHCL3; NARC1; LDLCQ1; NARC-1; HCHOLA3
    Summary
    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]
    Expression
    Biased expression in lung (RPKM 5.3), liver (RPKM 3.3) and 9 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See PCSK9 in Genome Data Viewer
    Location:
    1p32.3
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (55039548..55064852)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (55505221..55530525)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene transmembrane protein 61 Neighboring gene barttin CLCNK type accessory subunit beta Neighboring gene ubiquitin specific peptidase 24 Neighboring gene uncharacterized LOC100507634

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Professional guidelines

    Description
    Professional guideline
    ACMG 2013

    The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in PCSK9 that are pathogenic or expected to be pathogenic.

    GuidelinePubMed

    Associated conditions

    Description Tests
    A genome-wide association study identifies susceptibility loci for Wilms tumor.
    GeneReviews: Not available
    Biological, clinical and population relevance of 95 loci for blood lipids.
    GeneReviews: Not available
    Common variants at 30 loci contribute to polygenic dyslipidemia.
    GeneReviews: Not available
    Discovery and refinement of loci associated with lipid levels.
    GeneReviews: Not available
    Familial hypercholesterolemia Compare labs
    Familial hypercholesterolemia 3
    MedGen: C1863551 OMIM: 603776 GeneReviews: Familial Hypercholesterolemia
    Compare labs
    Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial.
    GeneReviews: Not available
    Genetic variants influencing circulating lipid levels and risk of coronary artery disease.
    GeneReviews: Not available
    Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.
    GeneReviews: Not available
    Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
    GeneReviews: Not available
    Genome-wide characterization of shared and distinct genetic components that influence blood lipid levels in ethnically diverse human populations.
    GeneReviews: Not available
    Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.
    GeneReviews: Not available
    Newly identified loci that influence lipid concentrations and risk of coronary artery disease.
    GeneReviews: Not available
    Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.
    GeneReviews: Not available
    Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
    GeneReviews: Not available

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2015-12-17)

    ClinGen Genome Curation Page
    Haploinsufficency

    Dosage sensitivity unlikely (Last evaluated 2015-12-17)

    ClinGen Genome Curation PagePubMed

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to insulin stimulus ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in cellular response to starvation ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in cholesterol homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cholesterol metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in kidney development ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in lipoprotein metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in liver development ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in low-density lipoprotein particle receptor catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in lysosomal transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of low-density lipoprotein particle clearance IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of low-density lipoprotein particle receptor binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of low-density lipoprotein receptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of receptor recycling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of receptor-mediated endocytosis involved in cholesterol transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of signaling receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of sodium ion transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in neurogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in neuron differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in phospholipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of low-density lipoprotein particle receptor catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of neuron apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of receptor internalization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein autoprocessing IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of signaling receptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in triglyceride metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in COPII-coated ER to Golgi transport vesicle IEA
    Inferred from Electronic Annotation
    more info
     
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of PCSK9-AnxA2 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of PCSK9-LDLR complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in early endosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in endolysosome membrane TAS
    Traceable Author Statement
    more info
     
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
     
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in extrinsic component of external side of plasma membrane IC
    Inferred by Curator
    more info
    PubMed 
    located_in late endosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in lysosomal membrane TAS
    Traceable Author Statement
    more info
     
    located_in lysosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in rough endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    proprotein convertase subtilisin/kexin type 9
    Names
    convertase subtilisin/kexin type 9 preproprotein
    neural apoptosis regulated convertase 1
    subtilisin/kexin-like protease PC9

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_009061.1 RefSeqGene

      Range
      4930..30307
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_275

    mRNA and Protein(s)

    1. NM_174936.4NP_777596.2  proprotein convertase subtilisin/kexin type 9 preproprotein

      See identical proteins and their annotated locations for NP_777596.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the functional protein.
      Source sequence(s)
      AC091609, AL589790, BC042095, DA738424, EF692496
      Consensus CDS
      CCDS603.1
      UniProtKB/Swiss-Prot
      Q8NBP7
      Related
      ENSP00000303208.5, ENST00000302118.5
      Conserved Domains (3) summary
      cd04077
      Location:156421
      Peptidases_S8_PCSK9_ProteinaseK_like; Peptidase S8 family domain in ProteinaseK-like proteins
      pfam00082
      Location:180422
      Peptidase_S8; Subtilase family
      pfam05922
      Location:77149
      Inhibitor_I9; Peptidase inhibitor I9

    RNA

    1. NR_110451.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate 5' terminal exon, lacks two internal exons, and uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      AC091609, AK297473, BC042095

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

      Range
      55039548..55064852
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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