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

Gene ID: 255738, updated on 17-Oct-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
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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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