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Tclin
PCSK9
Proprotein convertase subtilisin/kexin type 9

Protein Summary
Description
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 (PubMed:18039658). 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 (PubMed:18799458, PubMed:17461796, PubMed:18197702, PubMed:22074827). 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 (PubMed:18660751). Inhibi ...more
Uniprot Accession IDs
Gene Name
Ensembl ID
  • ENST00000302118
  • ENSP00000303208
  • ENSG00000169174

Symbol
  • NARC1
  • FH3
  • PC9
  • NARC1
  • LDLCQ1
  • NARC-1
  • HCHOLA3
Illumination Graph
Knowledge Table
Most Knowledge About
Knowledge Value (0 to 1 scale)
molecular function
0.98
biological process
0.97
ligand (protein) perturbation
0.83
disease
0.66
biological term
0.65


IDG Development Level Summary
Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3871.69   (req: < 5)
Gene RIFs: 412   (req: <= 3)
Antibodies: 572   (req: <= 50)
Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3871.69   (req: >= 5)
Gene RIFs: 412   (req: > 3)
Antibodies: 572   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 40
Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 21
Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2
Protein Sequence and Structure
Residue Counts
Protein Sequence
ProtVista Viewer
Related Tools
Target Illumination GWAS Analytics (TIGA)
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TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.
GENEVA
Thumbnail image for GENEVA
GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.
GlyGen
Thumbnail image for GlyGen
GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.
ARCHS4
Thumbnail image for ARCHS4
ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.
Approved Drugs (2)
1 – 2 of 2
evolocumab
no chemical structure image available
alirocumab
no chemical structure image available
Protein-Protein Interactions (241)
1 – 10 of 241
LDLR
Tchem
Novelty:  0.06585434
Score:  0.999
Data Source:  Reactome,STRINGDB
APOB
Tchem
Novelty:  0.00008247
Score:  0.992
Data Source:  STRINGDB
FN1
Tchem
Novelty:  0.00003647
Score:  0.988
Data Source:  STRINGDB
VLDLR
Tbio
Novelty:  0.00352547
Score:  0.975
Data Source:  Reactome,STRINGDB
APOE
Tbio
Novelty:  0.00005049
Score:  0.966
Data Source:  STRINGDB
MBTPS1
Tchem
Family:  Enzyme
Novelty:  0.00845881
Score:  0.965
Data Source:  STRINGDB
APOA5
Tbio
Novelty:  0.00232222
Score:  0.963
Data Source:  STRINGDB
APOA1
Tbio
Novelty:  0.0001216
Score:  0.96
Data Source:  STRINGDB
CALU
Tbio
Novelty:  0.01285123
Score:  0.943
Data Source:  STRINGDB
MIA3
Tbio
Novelty:  0.02784348
Score:  0.941
Data Source:  STRINGDB
Pathways (23)
LDL clearance (R-HSA-8964038)

Click on a row in the table to change the structure displayed.

Items per page:
1 – 5 of 9
Data Source
Name
Explore in Pharos
Explore in Source
Reactome
LDL clearance
Reactome
Metabolism of proteins
Reactome
Plasma lipoprotein assembly, remodeling, and clearance
Reactome
Plasma lipoprotein clearance
Reactome
Post-translational protein modification
Name
Explore in Pharos
Explore in Source
LDL clearance
Metabolism of proteins
Plasma lipoprotein assembly, remodeling, and clearance
Plasma lipoprotein clearance
Post-translational protein modification
Gene Ontology Terms (59)
Items per page:
10
1 – 10 of 11
GO Term
Evidence
Assigned by
Inferred from Direct Assay (IDA)
BHF-UCL
Inferred from Direct Assay (IDA)
HGNC
Inferred from Direct Assay (IDA)
UniProtKB
Inferred from Direct Assay (IDA)
BHF-UCL
Inferred from Direct Assay (IDA)
HGNC
Inferred from Direct Assay (IDA)
UniProtKB
Inferred from Direct Assay (IDA)
BHF-UCL
Inferred from High Throughput Direct Assay (HDA)
UniProtKB
Inferred from Sequence or structural Similarity (ISS)
UniProtKB
Inferred from Sequence or structural Similarity (ISS)
UniProtKB
GWAS Traits (18)
GWAS Trait
EFO ID
Study Count
SNP Count
Beta Count
Odds Ratio
Evidence (Mean Rank Score)
Provenance
low density lipoprotein cholesterol measurement
19
31
47
8
100
total cholesterol measurement
13
26
34
9.6
99.9
apolipoprotein B measurement
2
13
14
99.9
HMG CoA reductase inhibitor use measurement
1
3
3
94.6
blood metabolite measurement
1
2
2
93.7
GWAS Trait
EFO ID
Beta Count
Odds Ratio
Evidence (Mean Rank Score)
Provenance
low density lipoprotein cholesterol measurement
47
8
100
total cholesterol measurement
34
9.6
99.9
apolipoprotein B measurement
14
99.9
HMG CoA reductase inhibitor use measurement
3
94.6
blood metabolite measurement
2
93.7
Find similar targets by:
Orthologs (10)
1 – 5 of 10
Species
Name
Source ID
Gene ID
OMA
EggNOG
Inparanoid
Chimp
proprotein convertase subtilisin/kexin type 9
VGNC:9382
456880
Macaque
proprotein convertase subtilisin/kexin type 9
717147
Mouse
MGI:2140260
100102
Rat
RGD:728909
298296
Horse
proprotein convertase subtilisin/kexin type 9
VGNC:50739
100147049
Species
Name
OMA
EggNOG
Inparanoid
Chimp
proprotein convertase subtilisin/kexin type 9
Macaque
proprotein convertase subtilisin/kexin type 9
Mouse
Rat
Horse
proprotein convertase subtilisin/kexin type 9
Publication Statistics
PubMed Score 3871.69
PubMed score by year
PubTator Score 1682.39
PubTator score by year