PCSK9
proprotein convertase subtilisin/kexin type 9 | FH3, NARC-1, HCHOLA3

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]

Developmental clusters: GC7
Biological processes 79 terms
COPII-coated ER to Golgi transport vesicle (GO:0030134)Golgi apparatus (GO:0005794)Golgi apparatus (GO:0005794)PCSK9-AnxA2 complex (GO:1990667)PCSK9-LDLR complex (GO:1990666)RNA binding (GO:0003723)apolipoprotein binding (GO:0034185)apolipoprotein binding (GO:0034185)apolipoprotein receptor binding (GO:0034190)cell surface (GO:0009986)cell surface (GO:0009986)cellular response to insulin stimulus (GO:0032869)cellular response to insulin stimulus (GO:0032869)cellular response to starvation (GO:0009267)cellular response to starvation (GO:0009267)cholesterol homeostasis (GO:0042632)cholesterol homeostasis (GO:0042632)cholesterol homeostasis (GO:0042632)cytoplasm (GO:0005737)cytoplasm (GO:0005737)early endosome (GO:0005769)endolysosome membrane (GO:0036020)endopeptidase activity (GO:0004175)endoplasmic reticulum (GO:0005783)endoplasmic reticulum (GO:0005783)endoplasmic reticulum lumen (GO:0005788)endosome (GO:0005768)extracellular region (GO:0005576)extracellular region (GO:0005576)extracellular region (GO:0005576)extracellular region (GO:0005576)extrinsic component of external side of plasma membrane (GO:0031232)kidney development (GO:0001822)kidney development (GO:0001822)late endosome (GO:0005770)liver development (GO:0001889)liver development (GO:0001889)low-density lipoprotein particle binding (GO:0030169)low-density lipoprotein particle binding (GO:0030169)low-density lipoprotein particle receptor binding (GO:0050750)low-density lipoprotein particle receptor binding (GO:0050750)low-density lipoprotein particle receptor binding (GO:0050750)low-density lipoprotein particle receptor catabolic process (GO:0032802)lysosomal membrane (GO:0005765)lysosomal transport (GO:0007041)lysosome (GO:0005764)lysosome (GO:0005764)negative regulation of low-density lipoprotein particle clearance (GO:0010989)negative regulation of receptor internalization (GO:0002091)negative regulation of receptor recycling (GO:0001920)negative regulation of receptor-mediated endocytosis involved in cholesterol transport (GO:1905601)negative regulation of sodium ion import across plasma membrane (GO:1903783)neurogenesis (GO:0022008)neurogenesis (GO:0022008)neuron differentiation (GO:0030182)neuron differentiation (GO:0030182)perinuclear region of cytoplasm (GO:0048471)plasma membrane (GO:0005886)positive regulation of low-density lipoprotein particle receptor catabolic process (GO:0032805)positive regulation of neuron apoptotic process (GO:0043525)positive regulation of neuron apoptotic process (GO:0043525)positive regulation of receptor internalization (GO:0002092)protein autoprocessing (GO:0016540)protein autoprocessing (GO:0016540)protein binding (GO:0005515)protein processing (GO:0016485)proteolysis (GO:0006508)regulation of neuron apoptotic process (GO:0043523)regulation of neuron apoptotic process (GO:0043523)serine-type endopeptidase activity (GO:0004252)serine-type endopeptidase activity (GO:0004252)serine-type endopeptidase activity (GO:0004252)serine-type peptidase activity (GO:0008236)signaling receptor inhibitor activity (GO:0030547)sodium channel inhibitor activity (GO:0019871)transporter inhibitor activity (GO:0141110)very-low-density lipoprotein particle binding (GO:0034189)very-low-density lipoprotein particle binding (GO:0034189)very-low-density lipoprotein particle receptor binding (GO:0070326)
Expression (TPM)
PCSK9 — as a Regulated Gene

TFs regulating PCSK9 0 TFs

Transcription factors with Perturb-seq knockdown data for PCSK9. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = PCSK9 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to PCSK9

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of PCSK9, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr1:54,764,040–54,765,112 274.9 kb Distal (>10kb) Multiome 791
chr1:54,775,004–54,775,454 264.3 kb Distal (>10kb) Multiome 135
chr1:54,781,116–54,781,700 258.2 kb Distal (>10kb) Multiome 190
chr1:54,800,637–54,801,431 238.3 kb Distal (>10kb) Multiome 286
chr1:54,886,423–54,888,260 152.3 kb Distal (>10kb) Multiome 867
chr1:54,950,380–54,951,143 88.8 kb Distal (>10kb) Multiome 459
chr1:54,980,478–54,981,190 58.8 kb Distal (>10kb) Multiome 185
chr1:54,996,310–54,996,725 42.9 kb Distal (>10kb) Multiome 355
chr1:55,021,822–55,022,741 17.3 kb Distal (>10kb) Multiome 538
chr1:55,037,050–55,037,356 2.2 kb Proximal (<10kb) 7
chr1:55,039,084–55,041,196 93 bp At TSS Multiome 743
chr1:55,197,062–55,197,632 157.7 kb Distal (>10kb) Multiome 178
chr1:55,213,795–55,216,078 175.8 kb Distal (>10kb) Multiome 933
chr1:55,232,539–55,233,863 193.7 kb Distal (>10kb) Multiome 196
chr1:55,313,810–55,314,345 274.6 kb Distal (>10kb) Multiome 208
chr1:55,337,950–55,338,809 298.9 kb Distal (>10kb) Multiome 141

Genome Browser

Genomic view of the PCSK9 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr1:54,754,040 – 55,348,809
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq