Incidentalome

Gene: PCSK9

Green List (high evidence)

PCSK9 (proprotein convertase subtilisin/kexin type 9)
EnsemblGeneIds (GRCh38): ENSG00000169174
EnsemblGeneIds (GRCh37): ENSG00000169174
OMIM: 607786, Gene2Phenotype
PCSK9 is in 7 panels

2 reviews

Sangavi Sivagnanasundram (Melbourne Health)

Green List (high evidence)

Well established gene evidence supporting both modes of pathogenicity and its gene-disease correlation.

Gain of function is the main mechanism of disease for familial hypercholesterolemia (FH) in PCSK9 however loss of function in PCSK9 is causative of Low-density lipoprotein cholesterol level quantitative trait locus-1 (LDLCQ1).

PMID: 18354137 - Functional study using HEK293 cell lines was conducted to assess correlation between gain of function mutations and disease phenotype of FH. It was shown that the variants in PCSK9 caused excessive degradation of LDLR thus lowering the amount of LDL-C being removed from the blood.

PMID: 16909389 – An in vitro functional study using HEK293 cells was conducted and showed that loss of function mutations in the PCSK9 gene inhibits autocatalytic cleavage which affects PCSK9 protein secretion.

PMID: 15772090 – 12 individuals from 3 unrelated families carried the heterozygous D374Y pathogenic mutation in PCSK9 causative of familial hypercholesterolemia.
PMID: 12730697- Identified 12 members from 1 family with an S127R mutation causative of familial hypercholesterolemia.

PMID: 15654334 – Loss of function mutations in PCSK9 (common in African ancestry) are causative of Low-density lipoprotein cholesterol level quantitative trait locus-1 (LDLCQ1). The authors identified 3 unrelated individuals with a nonsense mutation (Y142X) in PCSK9 causative of LDLCQ1.
Created: 30 Mar 2023, 11:54 p.m. | Last Modified: 30 Mar 2023, 11:54 p.m.
Panel Version: 0.226

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Familial Hypercholesterolemia 3 (MONDO:0011369; MIM# 603776); Low-density lipoprotein cholesterol level quantitative trait locus-1 (LDLCQ1; MIM# 603776)

Publications

Mode of pathogenicity
Other

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypercholesterolemia, familial, 3, MIM# 603776

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review Green
  • Melbourne Genomics Health Alliance
  • Victorian Clinical Genetics Services
Phenotypes
  • Familial Hypercholesterolemia 3 (MONDO:0011369
  • MIM# 603776)
  • Low-density lipoprotein cholesterol level quantitative trait locus-1 (LDLCQ1
  • MIM# 603776)
Tags
treatable
OMIM
607786
Clinvar variants
Variants in PCSK9
Penetrance
None
Publications
Panels with this gene

History Filter Activity

31 Mar 2023, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: pcsk9 has been classified as Green List (High Evidence).

31 Mar 2023, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PCSK9 were changed from to Familial Hypercholesterolemia 3 (MONDO:0011369; MIM# 603776); Low-density lipoprotein cholesterol level quantitative trait locus-1 (LDLCQ1; MIM# 603776)

31 Mar 2023, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: PCSK9 were set to

31 Mar 2023, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: PCSK9 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

31 Mar 2023, Gel status: 3

Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag treatable tag was added to gene: PCSK9.

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: PCSK9 was added gene: PCSK9 was added to Incidentalome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: PCSK9 was set to Unknown