Gene: PCSK9

Alternate names for this Gene: FH3|FHCL3|HCHOLA3|LDLCQ1|NARC-1|NARC1|PC9

Gene 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.

Gene is located in Chromosome: 1

Location in Chromosome : 1p32.3

Description of this Gene: proprotein convertase subtilisin/kexin type 9

Type of Gene: protein-coding

rs11591147 in PCSK9 gene and Alcohol consumption PMID 30698716 2019 Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

rs11591147 in PCSK9 gene and Cardiovascular Diseases PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs11591147 in PCSK9 gene and Coronary Artery Disease PMID 30104761 2018 Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

PMID 28714975 2017 Association analyses based on false discovery rate implicate new loci for coronary artery disease.

PMID 29212778 2018 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.

rs11591147 in PCSK9 gene and Coronary heart disease PMID 21347282 2011 Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.

rs564427867 in PCSK9 gene and Familial hypercholesterolemia - homozygous PMID 20006333 2010 The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation.

PMID 24859021 2014 Clinical significance of measuring soluble LR11, a circulating marker of atherosclerosis and HbA1c in familial hypercholesterolemia.

PMID 26374825 2015 Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody.

PMID 21146822 2011 Molecular genetic epidemiology of homozygous familial hypercholesterolemia in the Hokuriku district of Japan.

PMID 25962062 2015 Genetic testing of Korean familial hypercholesterolemia using whole-exome sequencing.

PMID 17316651 2008 Genetic variants in PCSK9 in the Japanese population: rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population.

rs1057519691 in PCSK9 gene and HYPERCHOLESTEROLEMIA, AUTOSOMAL DOMINANT, 3 PMID 22683120 2012 Identification and characterization of new gain-of-function mutations in the PCSK9 gene responsible for autosomal dominant hypercholesterolemia.

PMID 12730697 2003 Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.

PMID 18799458 2008 Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels.

PMID 24808179 2014 Annexin A2 reduces PCSK9 protein levels via a translational mechanism and interacts with the M1 and M2 domains of PCSK9.

PMID 23788249 2013 ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.

PMID 27854360 2017 Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

PMID 25356965 2015 ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

PMID 19081568 2009 Degradation of LDLR protein mediated by 'gain of function' PCSK9 mutants in normal and ARH cells.

PMID 28777095 2017 PCSK 9 gain-of-function mutations (R496W and D374Y) and clinical cardiovascular characteristics in a cohort of Turkish patients with familial hypercholesterolemia.

PMID 23375686 2013 Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

PMID 27206942 2017 Proprotein convertase subtilisin/kexin 9 V4I variant with LDLR mutations modifies the phenotype of familial hypercholesterolemia.

PMID 16183066 2006 Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia.

PMID 26374825 2015 Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody.

PMID 20006333 2010 The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation.

PMID 25014035 2014 Genotypic and phenotypic features in homozygous familial hypercholesterolemia caused by proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutation.

PMID 27280970 2016 Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain.

PMID 17765244 2008 Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa.

PMID 23680767 2013 The use of next-generation sequencing in clinical diagnosis of familial hypercholesterolemia.

PMID 24607922 2014 The novel variant p.Ser465Leu in the PCSK9 gene does not account for the decreased LDLR activity in members of a FH family.

PMID 27896130 2016 Studies of the autoinhibitory segment comprising residues 31-60 of the prodomain of PCSK9: Possible implications for the mechanism underlying gain-of-function mutations.

PMID 18631360 2008 Investigations on the evolutionary conservation of PCSK9 reveal a functionally important protrusion.

PMID 18266662 2008 Characterization of novel mutations in the catalytic domain of the PCSK9 gene.

rs1057519691 in PCSK9 gene and Hypercholesterolemia, Familial PMID 27998977 2017 The Proprotein Convertase Subtilisin/Kexin Type 9-resistant R410S Low Density Lipoprotein Receptor Mutation: A NOVEL MECHANISM CAUSING FAMILIAL HYPERCHOLESTEROLEMIA.

PMID 24115837 2013 The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol.

PMID 26374825 2015 Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody.

PMID 22683120 2012 Identification and characterization of new gain-of-function mutations in the PCSK9 gene responsible for autosomal dominant hypercholesterolemia.

PMID 26036859 2016 Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction.

rs10888898 in PCSK9 gene and Low density lipoprotein cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 25961943 2015 The impact of low-frequency and rare variants on lipid levels.

PMID 30698716 2019 Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

PMID 24507774 2014 Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.

PMID 22629316 2012 Multi-ethnic analysis of lipid-associated loci: the NHLBI CARe project.

PMID 22460556 2012 As expected, the minor allele of the PCSK9 R46L variant was in all cohorts associated with reduced PCSK9 levels and decreased plasma low-density lipoprotein-cholesterol concentrations, but no relationship was observed with the plasma triglyceride concentration.

PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 18193044 2008 Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 30670697 2019 Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

PMID 30926973 2019 Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 23236364 2012 Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.

PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

PMID 30718733 2019 The Korea Biobank Array: Design and Identification of Coding Variants Associated with Blood Biochemical Traits.

PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.

PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.

PMID 28334899 2017 Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

PMID 31675503 2019 Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

rs2495478 in PCSK9 gene and Nephroblastoma PMID 22544364 2012 A genome-wide association study identifies susceptibility loci for Wilms tumor.

rs10888898 in PCSK9 gene and Serum LDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 22460556 2012 Common and low-frequency genetic variants in the PCSK9 locus influence circulating PCSK9 levels.

PMID 18193044 2008 Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.

PMID 22629316 2012 Multi-ethnic analysis of lipid-associated loci: the NHLBI CARe project.

PMID 23236364 2012 Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.

PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.

PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.

rs10888898 in PCSK9 gene and Serum total cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 28270201 2017 Exploration of haplotype research consortium imputation for genome-wide association studies in 20,032 Generation Scotland participants.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 23236364 2012 Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.

PMID 30718733 2019 The Korea Biobank Array: Design and Identification of Coding Variants Associated with Blood Biochemical Traits.

PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.

PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.

PMID 28334899 2017 Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

PMID 31675503 2019 Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

rs28362225 in PCSK9 gene and Triglycerides measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs11591147 in PCSK9 gene and response to statin PMID 22331829 2012 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.