• 40
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
PCSK9 (HGNC:20001) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
proprotein convertase subtilisin/kexin type 9
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
HCHOLA3
Alias symbols
NARC-1, FH3
%HI
73.06(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
1.34(Read more about gnomAD LOEUF score)
Cytoband
1p32.3
Genomic Coordinates
GRCh37/hg19: chr1:55505221-55530525 NCBI Ensembl UCSC
GRCh38/hg38: chr1:55039548-55064852 NCBI Ensembl UCSC
MANE Select Transcript
NM_174936.4 ENST00000302118.5 (Read more about MANE Select)
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 (PubMed:18039658). Acts via a non- proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-media... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-35301
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Dosage Sensitivity Unlikely (40)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
12/17/2015

Haploinsufficiency (HI) Score Details

HI Score:
40
HI Evidence Strength:
Dosage Sensitivity Unlikely (Disclaimer)
HI Evidence:
  • PUBMED: 19191301
    Nonsense mutations in PCSK9 appear to be polymorphic and confer susceptibility to low LDL cholesterol (hypocholesterolemia) whereas dominant missense mutations predispose to high LDL cholesterol.
  • PUBMED: 15654334
    African Americans carry two loss of function changes in PCSK9 with a combined frequency of 2%. These variants resulted in a 40% reduction in plasma levels of LDL cholesterol.
HI Evidence Comments:
Nonsense mutations in PCSK9 appear to be polymorphic and confer susceptibility to low LDL cholesterol (hypocholesterolemia) whereas dominant missense mutations predispose to high LDL cholesterol. There are also multiple reports of deletion CNVs at or near (and could be extending into depending on array resolution) PCSK9 in DGV. There are many PCSK9 frameshift and stop gain changes listed in ExAc (one at high frequency = 33 alleles = p.Tyr142Ter, rs67608943).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
There is no evidence at present for triplosensitivity of PCSK9.

Genomic View

Select assembly: (NC_000001.10) (NC_000001.11)