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

Gene ID: 255738, updated on 9-Nov-2014
Official Symbol
PCSK9provided by HGNC
Official Full Name
proprotein convertase subtilisin/kexin type 9provided by HGNC
Primary source
HGNC:HGNC:20001
Locus tag
PSEC0052
See related
Ensembl:ENSG00000169174; HPRD:07080; MIM:607786; Vega:OTTHUMG00000008136
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; 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]
See PCSK9 in Epigenomics, MapViewer
Location:
1p32.3
Exon count:
12
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 1 NC_000001.11 (55039476..55064853)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (55505149..55530526)

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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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
Hypercholesterolemia, autosomal dominant, 3
MedGen: C1863551 OMIM: 603776 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study identifies susceptibility loci for Wilms tumor.
NHGRI GWA Catalog
Biological, clinical and population relevance of 95 loci for blood lipids.
NHGRI GWA Catalog
Common variants at 30 loci contribute to polygenic dyslipidemia.
NHGRI GWA Catalog
Discovery and refinement of loci associated with lipid levels.
NHGRI GWA Catalog
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.
NHGRI GWA Catalog
Genetic variants influencing circulating lipid levels and risk of coronary artery disease.
NHGRI GWA Catalog
Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.
NHGRI GWA Catalog
Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
NHGRI GWA Catalog
Genome-wide characterization of shared and distinct genetic components that influence blood lipid levels in ethnically diverse human populations.
NHGRI GWA Catalog
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.
NHGRI GWA Catalog
Newly identified loci that influence lipid concentrations and risk of coronary artery disease.
NHGRI GWA Catalog
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.
NHGRI GWA Catalog
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
NHGRI GWA Catalog
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
apolipoprotein binding ISS
Inferred from Sequence or Structural Similarity
more info
 
apolipoprotein receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
low-density lipoprotein particle binding ISS
Inferred from Sequence or Structural Similarity
more info
 
low-density lipoprotein particle receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
low-density lipoprotein particle receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
poly(A) RNA binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein self-association IDA
Inferred from Direct Assay
more info
PubMed 
serine-type endopeptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
sodium channel inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
very-low-density lipoprotein particle binding ISS
Inferred from Sequence or Structural Similarity
more info
 
very-low-density lipoprotein particle receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
apoptotic process IEA
Inferred from Electronic Annotation
more info
 
cellular response to insulin stimulus ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cellular response to starvation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cholesterol homeostasis IMP
Inferred from Mutant Phenotype
more info
PubMed 
cholesterol metabolic process IEA
Inferred from Electronic Annotation
more info
 
kidney development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
lipoprotein metabolic process IEA
Inferred from Electronic Annotation
more info
 
liver development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
low-density lipoprotein particle receptor catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
lysosomal transport IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of low-density lipoprotein particle clearance IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of receptor recycling IDA
Inferred from Direct Assay
more info
PubMed 
neurogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
neuron differentiation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
phospholipid metabolic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of neuron apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of receptor internalization IDA
Inferred from Direct Assay
more info
PubMed 
protein autoprocessing IDA
Inferred from Direct Assay
more info
PubMed 
proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
 
regulation of low-density lipoprotein particle receptor catabolic process IEA
Inferred from Electronic Annotation
more info
 
regulation of neuron apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
triglyceride metabolic process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
ER to Golgi transport vesicle IEA
Inferred from Electronic Annotation
more info
 
Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
early endosome IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
extrinsic component of external side of plasma membrane IC
Inferred by Curator
more info
PubMed 
late endosome IDA
Inferred from Direct Assay
more info
PubMed 
lysosome IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
rough endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
 
Preferred Names
proprotein convertase subtilisin/kexin type 9
Names
proprotein convertase subtilisin/kexin type 9
subtilisin/kexin-like protease PC9
neural apoptosis regulated convertase 1
convertase subtilisin/kexin type 9 preproprotein
NP_777596.2

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 

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

mRNA and Protein(s)

  1. NM_174936.3NP_777596.2  proprotein convertase subtilisin/kexin type 9 preproprotein

    See proteins identical to 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, OTTHUMP00000009833, ENST00000302118, OTTHUMT00000022280
    Conserved Domains (3) summary
    cd04077
    Location:156421
    Peptidases_S8_PCSK9_ProteinaseK_like; Peptidase S8 family domain in ProteinaseK-like proteins
    pfam00082
    Location:182423
    Peptidase_S8; Subtilase family
    pfam05922
    Location:77152
    Inhibitor_I9; Peptidase inhibitor I9

RNA

  1. NR_110451.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate 5' structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC091609, AK297473, BC042095

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Alternate HuRef

Genomic

  1. AC_000133.1 

    Range
    53618200..53643557
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000001.11 

    Range
    55039476..55064853
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018912.2 

    Range
    55621314..55646685
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)