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PCSK9 (proprotein convertase subtilisin/kexin type 9)

Gene

255738

Proprotein convertase subtilisin/kexin type 9

PCSK9

FH3, FHCL3, HCHOLA3, LDLCQ1, NARC-1, NARC1, PC9

1p32.3

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]

Show/Hide all(44)

SNP ID	Visualize variation	Clinical significance	Consequence
rs509504	A>C,G,T	Likely-benign, benign, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, synonymous variant, coding sequence variant, missense variant
rs7552471	C>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign, benign	Non coding transcript variant, synonymous variant, missense variant, coding sequence variant
rs11583680	C>G,T	Pathogenic	Missense variant, genic upstream transcript variant, upstream transcript variant, coding sequence variant
rs11800243	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign, benign	Intron variant
rs28362201	G>C,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity, likely-benign	Genic upstream transcript variant, 5 prime UTR variant, upstream transcript variant
rs28362261	A>G	Benign, benign-likely-benign, likely-benign, uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, non coding transcript variant
rs28362286	C>A,T	Pathogenic, association, benign	Stop gained, coding sequence variant, synonymous variant, non coding transcript variant
rs28362287	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	3 prime UTR variant, non coding transcript variant
rs28385701	C>T	Benign, conflicting-interpretations-of-pathogenicity, likely-benign	Genic upstream transcript variant, coding sequence variant, synonymous variant, upstream transcript variant
rs28385710	C>T	Benign-likely-benign, conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant, non coding transcript variant
rs28942111	T>A	Pathogenic, likely-pathogenic	Coding sequence variant, intron variant, missense variant
rs28942112	T>C	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs35574083	GCTGCTGCT>-,GCT,GCTGCT,GCTGCTGCTGCT,GCTGCTGCTGCTGCT,GCTGCTGCTGCTGCTGCT,GCTGCTGCTGCTGCTGCTGCT,GCTGCTGCTGCTGCTGCTGCTGCT	Benign, benign-likely-benign, likely-benign, uncertain-significance, conflicting-interpretations-of-pathogenicity	Genic upstream transcript variant, coding sequence variant, inframe deletion, inframe insertion, upstream transcript variant
rs41297883	C>A,T	Benign, conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant, non coding transcript variant
rs67608943	C>G,T	Conflicting-interpretations-of-pathogenicity, association	Stop gained, synonymous variant, coding sequence variant, intron variant
rs137852912	G>A,C,T	Pathogenic-likely-pathogenic, pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs146471967	C>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant, non coding transcript variant
rs185392267	C>T	Pathogenic	Coding sequence variant, missense variant, intron variant
rs374603772	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant, non coding transcript variant
rs569379713	C>T	Pathogenic, uncertain-significance	Missense variant, intron variant, coding sequence variant
rs745633457	G>A,T	Pathogenic	Intron variant
rs753857795	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, missense variant
rs761767572	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs764603059	G>T	Pathogenic, uncertain-significance	Upstream transcript variant, missense variant, coding sequence variant, genic upstream transcript variant
rs768795323	G>A	Uncertain-significance, pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs772677312	C>G	Uncertain-significance, likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs778849441	C>A,G,T	Likely-pathogenic, pathogenic, uncertain-significance	Coding sequence variant, stop gained, missense variant, non coding transcript variant
rs793888521	G>A	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs794728683	G>A,T	Pathogenic, likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant, non coding transcript variant
rs886039839	C>A	Likely-pathogenic	Upstream transcript variant, missense variant, coding sequence variant, genic upstream transcript variant
rs886046435	G>A,C	Pathogenic, uncertain-significance	Non coding transcript variant, coding sequence variant, missense variant
rs986151799	G>A	Pathogenic	Synonymous variant, coding sequence variant, non coding transcript variant
rs1057519691	T>C,G	Likely-pathogenic, pathogenic	Missense variant, intron variant, coding sequence variant
rs1254346075	G>A,T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1272703401	G>A	Pathogenic	Intron variant, upstream transcript variant, genic upstream transcript variant
rs1278890129	G>A	Pathogenic, uncertain-significance	Upstream transcript variant, coding sequence variant, genic upstream transcript variant, missense variant
rs1372204035	C>G	Pathogenic	Coding sequence variant, missense variant, upstream transcript variant, genic upstream transcript variant
rs1553135400	G>A	Pathogenic	Upstream transcript variant, coding sequence variant, missense variant, genic upstream transcript variant
rs1553135406	C>-	Likely-pathogenic, pathogenic	Upstream transcript variant, frameshift variant, coding sequence variant, genic upstream transcript variant
rs1553135930	A>C	Pathogenic	Intron variant, coding sequence variant, missense variant
rs1553135971	A>G	Likely-pathogenic, uncertain-significance	Intron variant, coding sequence variant, missense variant
rs1553137543	A>T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1553137693	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1553137699	G>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant

Show/Hide all(129)

miRTarBase ID	miRNA	Experiments	Reference
MIRT018980	hsa-miR-335-5p	Microarray	18185580
MIRT023073	hsa-miR-124-3p	Microarray	18668037
MIRT024487	hsa-miR-215-5p	Microarray	19074876
MIRT026924	hsa-miR-192-5p	Microarray	19074876
MIRT459645	hsa-miR-6864-5p	PAR-CLIP	23592263
MIRT459645	hsa-miR-6864-5p	PAR-CLIP	26701625
MIRT459645	hsa-miR-6864-5p	PAR-CLIP	27292025
MIRT459646	hsa-miR-6515-5p	PAR-CLIP	23592263
MIRT459646	hsa-miR-6515-5p	PAR-CLIP	26701625
MIRT459646	hsa-miR-6515-5p	PAR-CLIP	27292025
MIRT459647	hsa-miR-4656	PAR-CLIP	23592263
MIRT459647	hsa-miR-4656	PAR-CLIP	26701625
MIRT459647	hsa-miR-4656	PAR-CLIP	27292025
MIRT459648	hsa-miR-6797-5p	PAR-CLIP	23592263
MIRT459648	hsa-miR-6797-5p	PAR-CLIP	26701625
MIRT459648	hsa-miR-6797-5p	PAR-CLIP	27292025
MIRT459649	hsa-miR-1249-5p	PAR-CLIP	23592263
MIRT459649	hsa-miR-1249-5p	PAR-CLIP	26701625
MIRT459649	hsa-miR-1249-5p	PAR-CLIP	27292025
MIRT459650	hsa-miR-6875-5p	PAR-CLIP	23592263
MIRT459650	hsa-miR-6875-5p	PAR-CLIP	26701625
MIRT459650	hsa-miR-6875-5p	PAR-CLIP	27292025
MIRT459651	hsa-miR-4721	PAR-CLIP	23592263
MIRT459651	hsa-miR-4721	PAR-CLIP	26701625
MIRT459651	hsa-miR-4721	PAR-CLIP	27292025
MIRT459652	hsa-miR-6761-5p	PAR-CLIP	23592263
MIRT459652	hsa-miR-6761-5p	PAR-CLIP	26701625
MIRT459652	hsa-miR-6761-5p	PAR-CLIP	27292025
MIRT459653	hsa-miR-3126-5p	PAR-CLIP	23592263
MIRT459653	hsa-miR-3126-5p	PAR-CLIP	26701625
MIRT459653	hsa-miR-3126-5p	PAR-CLIP	27292025
MIRT459654	hsa-miR-4802-5p	PAR-CLIP	23592263
MIRT459654	hsa-miR-4802-5p	PAR-CLIP	26701625
MIRT459654	hsa-miR-4802-5p	PAR-CLIP	27292025
MIRT459655	hsa-miR-4446-3p	PAR-CLIP	23592263
MIRT459655	hsa-miR-4446-3p	PAR-CLIP	26701625
MIRT459655	hsa-miR-4446-3p	PAR-CLIP	27292025
MIRT459656	hsa-miR-6873-5p	PAR-CLIP	23592263
MIRT459656	hsa-miR-6873-5p	PAR-CLIP	26701625
MIRT459656	hsa-miR-6873-5p	PAR-CLIP	27292025
MIRT459657	hsa-miR-7845-5p	PAR-CLIP	23592263
MIRT459657	hsa-miR-7845-5p	PAR-CLIP	26701625
MIRT459657	hsa-miR-7845-5p	PAR-CLIP	27292025
MIRT459658	hsa-miR-6856-5p	PAR-CLIP	23592263
MIRT459658	hsa-miR-6856-5p	PAR-CLIP	26701625
MIRT459658	hsa-miR-6856-5p	PAR-CLIP	27292025
MIRT459659	hsa-miR-6758-5p	PAR-CLIP	23592263
MIRT459659	hsa-miR-6758-5p	PAR-CLIP	26701625
MIRT459659	hsa-miR-6758-5p	PAR-CLIP	27292025
MIRT459660	hsa-miR-6882-5p	PAR-CLIP	23592263
MIRT459660	hsa-miR-6882-5p	PAR-CLIP	26701625
MIRT459660	hsa-miR-6882-5p	PAR-CLIP	27292025
MIRT499825	hsa-miR-1303	PAR-CLIP	24398324
MIRT499825	hsa-miR-1303	PAR-CLIP	23446348
MIRT499825	hsa-miR-1303	PAR-CLIP	21572407
MIRT499825	hsa-miR-1303	PAR-CLIP	20371350
MIRT499826	hsa-miR-744-3p	PAR-CLIP	24398324
MIRT499826	hsa-miR-744-3p	PAR-CLIP	23446348
MIRT499826	hsa-miR-744-3p	PAR-CLIP	21572407
MIRT499826	hsa-miR-744-3p	PAR-CLIP	20371350
MIRT499827	hsa-miR-6501-5p	PAR-CLIP	24398324
MIRT499827	hsa-miR-6501-5p	PAR-CLIP	23446348
MIRT499827	hsa-miR-6501-5p	PAR-CLIP	21572407
MIRT499827	hsa-miR-6501-5p	PAR-CLIP	20371350
MIRT499828	hsa-miR-4423-5p	PAR-CLIP	24398324
MIRT499828	hsa-miR-4423-5p	PAR-CLIP	23446348
MIRT499828	hsa-miR-4423-5p	PAR-CLIP	21572407
MIRT499828	hsa-miR-4423-5p	PAR-CLIP	20371350
MIRT499829	hsa-miR-193a-5p	PAR-CLIP	24398324
MIRT499829	hsa-miR-193a-5p	PAR-CLIP	23446348
MIRT499829	hsa-miR-193a-5p	PAR-CLIP	21572407
MIRT499830	hsa-miR-367-5p	PAR-CLIP	24398324
MIRT499830	hsa-miR-367-5p	PAR-CLIP	23446348
MIRT499830	hsa-miR-367-5p	PAR-CLIP	21572407
MIRT499830	hsa-miR-367-5p	PAR-CLIP	20371350
MIRT499831	hsa-miR-6764-5p	PAR-CLIP	24398324
MIRT499831	hsa-miR-6764-5p	PAR-CLIP	23446348
MIRT499831	hsa-miR-6764-5p	PAR-CLIP	21572407
MIRT499831	hsa-miR-6764-5p	PAR-CLIP	20371350
MIRT499832	hsa-miR-1304-3p	PAR-CLIP	24398324
MIRT499832	hsa-miR-1304-3p	PAR-CLIP	23446348
MIRT499832	hsa-miR-1304-3p	PAR-CLIP	21572407
MIRT499832	hsa-miR-1304-3p	PAR-CLIP	20371350
MIRT499833	hsa-miR-1915-3p	PAR-CLIP	24398324
MIRT499833	hsa-miR-1915-3p	PAR-CLIP	23446348
MIRT499833	hsa-miR-1915-3p	PAR-CLIP	21572407
MIRT499833	hsa-miR-1915-3p	PAR-CLIP	20371350
MIRT499834	hsa-miR-1208	PAR-CLIP	24398324
MIRT499834	hsa-miR-1208	PAR-CLIP	23446348
MIRT499834	hsa-miR-1208	PAR-CLIP	21572407
MIRT499834	hsa-miR-1208	PAR-CLIP	20371350
MIRT499835	hsa-miR-3976	PAR-CLIP	24398324
MIRT499835	hsa-miR-3976	PAR-CLIP	23446348
MIRT499835	hsa-miR-3976	PAR-CLIP	21572407
MIRT499835	hsa-miR-3976	PAR-CLIP	20371350
MIRT499836	hsa-miR-6760-3p	PAR-CLIP	24398324
MIRT499836	hsa-miR-6760-3p	PAR-CLIP	23446348
MIRT499836	hsa-miR-6760-3p	PAR-CLIP	21572407
MIRT499836	hsa-miR-6760-3p	PAR-CLIP	20371350
MIRT499837	hsa-miR-1182	PAR-CLIP	24398324
MIRT499837	hsa-miR-1182	PAR-CLIP	23446348
MIRT499837	hsa-miR-1182	PAR-CLIP	21572407
MIRT499838	hsa-miR-483-5p	PAR-CLIP	24398324
MIRT499838	hsa-miR-483-5p	PAR-CLIP	23446348
MIRT499838	hsa-miR-483-5p	PAR-CLIP	21572407
MIRT499838	hsa-miR-483-5p	PAR-CLIP	20371350
MIRT569908	hsa-miR-7107-5p	PAR-CLIP	20371350
MIRT569909	hsa-miR-6763-5p	PAR-CLIP	20371350
MIRT569910	hsa-miR-3150a-3p	PAR-CLIP	20371350
MIRT569911	hsa-miR-6825-5p	PAR-CLIP	20371350
MIRT569912	hsa-miR-939-5p	PAR-CLIP	20371350
MIRT569913	hsa-miR-1343-5p	PAR-CLIP	20371350
MIRT569914	hsa-miR-3175	PAR-CLIP	20371350
MIRT569915	hsa-miR-7106-5p	PAR-CLIP	20371350
MIRT569916	hsa-miR-650	PAR-CLIP	20371350
MIRT569917	hsa-miR-3612	PAR-CLIP	20371350
MIRT569918	hsa-miR-765	PAR-CLIP	20371350
MIRT569919	hsa-miR-4700-5p	PAR-CLIP	20371350
MIRT569920	hsa-miR-8089	PAR-CLIP	20371350
MIRT569921	hsa-miR-4667-5p	PAR-CLIP	20371350
MIRT569922	hsa-miR-6852-5p	PAR-CLIP	20371350
MIRT569923	hsa-miR-759	PAR-CLIP	20371350
MIRT569924	hsa-miR-500b-3p	PAR-CLIP	20371350
MIRT569925	hsa-miR-3174	PAR-CLIP	20371350
MIRT569926	hsa-miR-4695-5p	PAR-CLIP	20371350
MIRT569927	hsa-miR-5586-3p	PAR-CLIP	20371350
MIRT569928	hsa-miR-7851-3p	PAR-CLIP	20371350
MIRT569929	hsa-miR-1912	PAR-CLIP	20371350
MIRT569930	hsa-miR-1295b-5p	PAR-CLIP	20371350

Transcription factors

Show/Hide all(3)

Transcription factor	Regulation	Reference
HNF4A	Activation	21123766
SREBF1	Activation	17921436
SREBF2	Activation	17448444;17921436;21123766;22288532

Show/Hide all(65)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001822	Process	Kidney development	ISS	12552133
GO:0001889	Process	Liver development	ISS	12552133
GO:0001920	Process	Negative regulation of receptor recycling	IDA	17452316, 22848640
GO:0002092	Process	Positive regulation of receptor internalization	IDA	17328821
GO:0003723	Function	RNA binding	HDA	22658674
GO:0004252	Function	Serine-type endopeptidase activity	IBA	21873635
GO:0004252	Function	Serine-type endopeptidase activity	IDA	12552133
GO:0005515	Function	Protein binding	IPI	17461796, 18799458, 22081141, 22493497, 22580899, 22848640, 25613181
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	12552133, 16912035, 17080197
GO:0005737	Component	Cytoplasm	IDA	22580899
GO:0005764	Component	Lysosome	IDA	17461796, 18039658
GO:0005765	Component	Lysosomal membrane	TAS
GO:0005769	Component	Early endosome	IDA	17461796
GO:0005770	Component	Late endosome	IDA	17461796, 18039658
GO:0005783	Component	Endoplasmic reticulum	IDA	17461796
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005791	Component	Rough endoplasmic reticulum	IEA
GO:0005794	Component	Golgi apparatus	IDA	17461796
GO:0005886	Component	Plasma membrane	IDA	18799458
GO:0006641	Process	Triglyceride metabolic process	IEA
GO:0006644	Process	Phospholipid metabolic process	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0007041	Process	Lysosomal transport	IDA	17452316
GO:0008203	Process	Cholesterol metabolic process	IEA
GO:0009267	Process	Cellular response to starvation	ISS	16407292
GO:0009986	Component	Cell surface	IDA	17461796
GO:0010469	Process	Regulation of signaling receptor activity	IDA	17328821
GO:0010989	Process	Negative regulation of low-density lipoprotein particle clearance	IDA	17328821, 22848640
GO:0016540	Process	Protein autoprocessing	IDA	14622975
GO:0019871	Function	Sodium channel inhibitor activity	IDA	22493497
GO:0022008	Process	Neurogenesis	ISS	12552133
GO:0030134	Component	COPII-coated ER to Golgi transport vesicle	IEA
GO:0030169	Function	Low-density lipoprotein particle binding	ISS
GO:0030182	Process	Neuron differentiation	ISS	12552133
GO:0030547	Function	Receptor inhibitor activity	IDA	22848640
GO:0031232	Component	Extrinsic component of external side of plasma membrane	IC	17328821
GO:0032802	Process	Low-density lipoprotein particle receptor catabolic process	IDA	16912035, 18197702
GO:0032802	Process	Low-density lipoprotein particle receptor catabolic process	TAS
GO:0032805	Process	Positive regulation of low-density lipoprotein particle receptor catabolic process	IDA	22848640
GO:0032869	Process	Cellular response to insulin stimulus	ISS	12552133
GO:0034185	Function	Apolipoprotein binding	ISS
GO:0034189	Function	Very-low-density lipoprotein particle binding	ISS
GO:0034190	Function	Apolipoprotein receptor binding	IDA	18039658
GO:0034383	Process	Low-density lipoprotein particle clearance	TAS
GO:0036020	Component	Endolysosome membrane	TAS
GO:0042157	Process	Lipoprotein metabolic process	IEA
GO:0042632	Process	Cholesterol homeostasis	IMP	17170371
GO:0043523	Process	Regulation of neuron apoptotic process	ISS
GO:0043525	Process	Positive regulation of neuron apoptotic process	IMP	17051583
GO:0043621	Function	Protein self-association	IDA	18197702
GO:0043687	Process	Post-translational protein modification	TAS
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	18039658
GO:0050750	Function	Low-density lipoprotein particle receptor binding	IDA	17080197
GO:0050750	Function	Low-density lipoprotein particle receptor binding	IPI	17452316, 22848640
GO:0070326	Function	Very-low-density lipoprotein particle receptor binding	IDA	18039658
GO:1905596	Process	Negative regulation of low-density lipoprotein particle receptor binding	IDA	22848640
GO:1905598	Process	Negative regulation of low-density lipoprotein receptor activity	IDA	22848640
GO:1905601	Process	Negative regulation of receptor-mediated endocytosis involved in cholesterol transport	IDA	22848640
GO:1990666	Component	PCSK9-LDLR complex	IDA	22848640
GO:1990667	Component	PCSK9-AnxA2 complex	IDA	22848640
GO:2000272	Process	Negative regulation of signaling receptor activity	IEA
GO:2000650	Process	Negative regulation of sodium ion transmembrane transporter activity	IDA	22493497

MIM	HGNC	e!Ensembl
607786	20001	ENSG00000169174

Protein

UniProt ID

Q8NBP7

Protein name

Proprotein convertase subtilisin/kexin type 9 (EC 3.4.21.-) (Neural apoptosis-regulated convertase 1) (NARC-1) (Proprotein convertase 9) (PC9) (Subtilisin/kexin-like protease PC9)

Protein 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-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). Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.

PDB

2P4E , 2PMW , 2QTW , 2W2M , 2W2N , 2W2O , 2W2P , 2W2Q , 2XTJ , 3BPS , 3GCW , 3GCX , 3H42 , 3M0C , 3P5B , 3P5C , 3SQO , 4K8R , 4NE9 , 4NMX , 4OV6 , 5OCA , 5VL7 , 5VLA , 5VLH , 5VLK , 5VLL , 5VLP , 6E4Y , 6E4Z , 6F5G , 6MV5 , 6OLZ , 6OM0 , 6OM7 , 6U26 , 6U2F , 6U2N , 6U2P , 6U36 , 6U38 , 6U3I , 6U3X

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF05922	Inhibitor_I9	77 → 152	Peptidase inhibitor I9	Domain
PF00082	Peptidase_S8	177 → 436	Subtilase family	Domain
PF18459	PCSK9_C1	449 → 531	Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain	Domain
PF18464	PCSK9_C2	535 → 600	Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain	Domain
PF18463	PCSK9_C3	602 → 682	Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain	Domain

Sequence

MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGT
TATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLP
GFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLV
EVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAG
VAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAA
CQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVD
LFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA
KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPD
EELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAP
PAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASC
CHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRD
VSTTGSTSEGAVTAVAICCRSRHLAQASQELQ

Sequence length

692

Interactions

View interactions

	KEGG		Reactome
	Cholesterol metabolism		Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) VLDLR internalisation and degradation Post-translational protein phosphorylation LDL clearance

Associated diseases

Show/Hide Causal Diseases (10)

Causal
Disease name	Disease term	dbSNP ID	References
Hyperlipoproteinemia	Hyperlipoproteinemia Type IIa	rs118204056, rs-1, rs118204057, rs118204058, rs118204059, rs1563572716, rs118204060, rs118204067, rs118204062, rs118204074, rs118204063, rs118204064, rs1563569634, rs118204065, rs118204066, rs1563575252, rs118204068, rs118204069, rs118204070, rs766134215, rs118204071, rs118204072, rs118204073, rs118204075, rs118204076, rs118204077, rs118204078, rs118204079, rs118204080, rs118204081, rs118204082, rs121917821, rs121918393, rs397514253, rs397514254, rs121918394, rs2122132718, rs121918396, rs121918397, rs387906567, rs587777637, rs587777638, rs587777639, rs587777640, rs587777641, rs587777642, rs587777643, rs886037774, rs201079485, rs1554517725, rs371282890, rs35414700
Hyperlipidemia	Hyperlipidemia	rs118204057, rs118204060, rs118204062, rs1563569634, rs118204069, rs118204070, rs118204071, rs3737787, rs2073658, rs1566946168, rs1064797075
Hypercholesterolemia	Hypercholesterolemia, Hypercholesterolemia, Familial, Familial hypercholesterolemia - homozygous, HYPERCHOLESTEROLEMIA, AUTOSOMAL DOMINANT, 3, NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia	rs28942111, rs28942112, rs137852912, rs-1, rs121908025, rs28942082, rs28942083, rs121908028, rs121908030, rs28942079, rs28942084, rs121908032, rs387906302, rs387906303, rs121908033, rs121908034, rs387906304, rs387906305, rs121908036, rs387906306, rs121908037, rs200238879, rs121908040, rs267607213, rs121908041, rs121908042, rs145787161, rs121908043, rs121908044, rs121908324, rs1557703339, rs121908325, rs1553170279, rs755104973, rs1461905374, rs781585299, rs751141, rs121918386, rs587776886, rs193922566, rs137943601, rs193922567, rs193922569, rs193922571, rs144467873, rs137853966, rs137853965, rs377271627, rs144172724, rs139043155, rs368657165, rs146200173, rs368562025, rs139624145, rs370777955, rs373646964, rs137929307, rs374045590, rs139617694, rs730880131, rs730880130, rs730882080, rs200727689, rs557344672, rs730882085, rs730882086, rs730882090, rs544453230, rs730882098, rs570942190, rs193922568, rs730882102, rs730882109, rs201102492, rs730882110, rs793888522, rs793888517, rs146651743, rs794728683, rs794728585, rs376459828, rs768563000, rs794728584, rs375009082, rs869025453, rs869025454, rs758194385, rs769446356, rs869320649, rs869320652, rs875989888, rs551747280, rs544203837, rs875989889, rs875989890, rs875989891, rs875989893, rs875989894, rs771019366, rs563390335, rs875989895, rs875989896, rs875989897, rs875989898, rs769383881, rs875989900, rs537484504, rs875989901, rs199774121, rs875989902, rs875989903, rs121908027, rs875989905, rs875989906, rs577934998, rs121908029, rs875989907, rs875989908, rs875989909, rs11547917, rs875989911, rs875989910, rs875989912, rs761954844, rs875989914, rs767767730, rs875989915, rs875989916, rs875989917, rs765696008, rs552422789, rs28942078, rs875989919, rs875989920, rs875989921, rs875989922, rs875989925, rs875989926, rs875989927, rs875989928, rs875989929, rs875989930, rs875989932, rs370245937, rs875989934, rs875989935, rs875989936, rs875989937, rs775092314, rs875989938, rs875989941, rs875989943, rs750518671, rs28942085, rs876657697, rs756039188, rs878854026, rs878854028, rs878854027, rs879254363, rs879254368, rs879254374, rs879254382, rs879254383, rs879254384, rs201016593, rs879254386, rs879254385, rs879254387, rs879254388, rs879254390, rs879254393, rs879254394, rs879254395, rs879254396, rs879254397, rs879254398, rs879254399, rs879254400, rs2228671, rs879254401, rs776421777, rs879254402, rs879254403, rs879254404, rs879254405, rs879254406, rs879254407, rs879254408, rs879254409, rs879254410, rs879254411, rs879254412, rs879254413, rs879254414, rs879254415, rs754676104, rs387906301, rs879254417, rs879254418, rs879254419, rs879254423, rs879254422, rs879254424, rs879254425, rs879254426, rs879254428, rs879254430, rs879254432, rs879254433, rs879254434, rs1555802710, rs879254435, rs879254436, rs879254437, rs879254438, rs879254439, rs758927662, rs879254440, rs879254442, rs879254443, rs879254445, rs879254447, rs879254446, rs879254448, rs879254452, rs199570811, rs879254453, rs879254455, rs777640882, rs749038326, rs372828849, rs745776977, rs879254456, rs879254457, rs139400379, rs372845091, rs879254458, rs879254459, rs879254460, rs879254461, rs764797225, rs879254464, rs879254463, rs879254465, rs112029328, rs879254466, rs879254467, rs879254470, rs879254471, rs879254472, rs879254475, rs879254476, rs879254477, rs879254478, rs879254479, rs879254480, rs879254481, rs774723292, rs879254482, rs879254485, rs879254483, rs879254484, rs879254487, rs879254488, rs879254489, rs879254490, rs879254491, rs879254492, rs879254493, rs879254494, rs879254496, rs879254497, rs879254499, rs875989899, rs879254500, rs879254501, rs879254502, rs879254503, rs879254505, rs879254504, rs879254506, rs879254507, rs879254509, rs879254510, rs879254512, rs879254514, rs879254515, rs879254516, rs755799528, rs879254517, rs879254518, rs748944640, rs879254519, rs879254520, rs879254521, rs879254522, rs879254523, rs879254524, rs879254525, rs879254526, rs879254528, rs879254530, rs879254531, rs879254532, rs879254533, rs879254534, rs879254535, rs879254536, rs766094434, rs879254537, rs879254538, rs763998635, rs879254540, rs879254542, rs879254543, rs879254545, rs879254546, rs879254547, rs879254548, rs752596535, rs879254549, rs879254550, rs879254551, rs879254552, rs879254554, rs879254555, rs879254557, rs879254556, rs879254558, rs879254560, rs879254559, rs769318035, rs879254561, rs879254562, rs879254563, rs879254565, rs879254564, rs879254566, rs879254567, rs879254568, rs879254569, rs879254570, rs879254572, rs879254571, rs879254573, rs879254574, rs879254575, rs879254577, rs879254579, rs879254580, rs879254581, rs879254582, rs879254584, rs748672083, rs879254588, rs879254591, rs879254592, rs879254593, rs879254594, rs879254595, rs879254596, rs879254597, rs879254598, rs879254599, rs879254600, rs771917370, rs879254602, rs879254605, rs879254606, rs764042910, rs879254607, rs879254608, rs879254610, rs879254609, rs879254611, rs879254612, rs879254613, rs879254614, rs879254615, rs879254616, rs879254358, rs1555803428, rs879254619, rs373822756, rs879254620, rs879254622, rs756613387, rs879254623, rs879254624, rs1555803424, rs879254627, rs879254625, rs879254626, rs879254628, rs879254629, rs879254630, rs1555803414, rs879254631, rs1555803423, rs1555803426, rs879254632, rs879254633, rs879254635, rs879254634, rs879254636, rs879254638, rs1555803427, rs879254639, rs879254640, rs879254641, rs879254642, rs746091400, rs879254644, rs121908035, rs879254645, rs879254646, rs879254647, rs879254651, rs879254652, rs1555803643, rs1555803644, rs879254653, rs879254655, rs879254656, rs879254658, rs879254659, rs879254660, rs879254662, rs879254663, rs879254664, rs879254666, rs759109699, rs879254667, rs879254668, rs879254669, rs879254670, rs879254671, rs879254672, rs879254673, rs879254674, rs879254675, rs879254677, rs879254678, rs879254681, rs879254682, rs879254683, rs773328511, rs879254684, rs879254685, rs879254686, rs879254688, rs879254689, rs879254691, rs879254692, rs730882089, rs879254693, rs140241383, rs375495026, rs879254697, rs879254696, rs879254699, rs879254700, rs879254701, rs879254702, rs879254703, rs879254704, rs879254705, rs879254706, rs879254708, rs879254710, rs879254712, rs767618089, rs879254713, rs879254714, rs879254716, rs879254717, rs757252110, rs879254718, rs879254719, rs879254720, rs879254721, rs879254723, rs879254725, rs879254727, rs879254728, rs13306512, rs879254729, rs879254734, rs112366278, rs879254735, rs879254736, rs746834464, rs879254737, rs879254738, rs879254739, rs879254740, rs879254743, rs879254744, rs879254745, rs879254746, rs879254747, rs879254748, rs879254749, rs767024374, rs879254751, rs879254752, rs879254753, rs879254754, rs879254755, rs879254757, rs755757866, rs879254758, rs777524402, rs730882096, rs879254760, rs879254761, rs879254762, rs879254763, rs879254764, rs748300548, rs879254765, rs879254767, rs879254768, rs879254769, rs13306515, rs879254770, rs879254771, rs879254773, rs879254774, rs755449669, rs879254775, rs879254777, rs879254778, rs879254781, rs879254780, rs879254782, rs879254783, rs879254784, rs879254786, rs879254788, rs879254789, rs746982741, rs879254791, rs768430352, rs113669610, rs879254792, rs879254794, rs879254796, rs879254797, rs879254799, rs1555804777, rs879254800, rs773064328, rs879254801, rs879254802, rs1555804793, rs879254804, rs879254805, rs879254807, rs879254806, rs879254811, rs879254812, rs879254814, rs879254813, rs879254815, rs879254816, rs879254817, rs879254820, rs879254819, rs879254821, rs879254823, rs879254824, rs879254826, rs879254827, rs879254828, rs879254829, rs879254830, rs879254832, rs879254833, rs879254835, rs879254837, rs879254838, rs879254839, rs879254840, rs879254841, rs879254842, rs879254844, rs879254846, rs773658037, rs869320651, rs774439908, rs879254848, rs879254849, rs879254850, rs879254851, rs879254854, rs879254855, rs879254856, rs745343524, rs879254857, rs879254858, rs779732323, rs879254859, rs879254862, rs879254863, rs879254864, rs879254865, rs879254866, rs879254867, rs879254868, rs879254869, rs879254872, rs879254873, rs879254874, rs775924858, rs879254875, rs531005522, rs879254879, rs879254880, rs879254881, rs879254882, rs879254883, rs879254884, rs879254885, rs879254886, rs879254887, rs879254888, rs879254892, rs879254893, rs201967266, rs879254896, rs879254898, rs879254899, rs879254901, rs879254902, rs879254904, rs879254907, rs879254906, rs879254913, rs879254915, rs879254916, rs879254918, rs879254919, rs751603969, rs879254921, rs879254922, rs879254923, rs755667663, rs879254924, rs730882103, rs879254927, rs879254929, rs879254930, rs879254931, rs879254932, rs879254933, rs879254935, rs879254939, rs879254941, rs755389753, rs879254945, rs879254947, rs879254948, rs879254949, rs879254950, rs879254951, rs746939188, rs879254952, rs879254955, rs879254956, rs879254957, rs879254958, rs879254959, rs769370816, rs879254962, rs879254963, rs879254964, rs879254965, rs759876319, rs879254966, rs28942081, rs879254967, rs879254970, rs879254969, rs879254971, rs28941776, rs879254973, rs879254972, rs879254975, rs879254976, rs879254977, rs879254978, rs879254979, rs879254980, rs879254981, rs879254982, rs879254985, rs879254984, rs879254986, rs879254988, rs879254989, rs746959386, rs879254990, rs879254991, rs879254994, rs879254996, rs879254998, rs879254999, rs879255000, rs138947766, rs879255001, rs879255003, rs879255004, rs879255005, rs879255006, rs879255007, rs879255009, rs879255008, rs879255011, rs879255012, rs879255013, rs879255014, rs879255015, rs879255016, rs875989931, rs879255019, rs879255020, rs879255021, rs879255022, rs879255026, rs753707206, rs879255027, rs879255028, rs879255029, rs879255031, rs879255032, rs879255033, rs879255034, rs879255035, rs879255038, rs879255037, rs879255039, rs879255041, rs879255044, rs879255046, rs879255049, rs879255050, rs879255051, rs879255052, rs747134711, rs879255053, rs879255054, rs879255055, rs875989933, rs879255057, rs879255058, rs879255059, rs879255060, rs879255061, rs879255063, rs879255065, rs879255066, rs879255069, rs879255068, rs879255070, rs754536745, rs879255073, rs879255076, rs879255077, rs879255078, rs879255079, rs879255082, rs1555807275, rs879255088, rs879255089, rs879255090, rs879255092, rs773693079, rs879255093, rs879255096, rs879255097, rs879255098, rs1555807306, rs879255101, rs879255102, rs879255104, rs752935814, rs879255106, rs150021927, rs879255107, rs879255109, rs879255108, rs879255110, rs879255112, rs770744861, rs745753810, rs879255113, rs879255114, rs879255115, rs879255116, rs879255117, rs760436036, rs879255118, rs201637900, rs121908031, rs879255120, rs879255121, rs2569548, rs879255122, rs879255123, rs879255124, rs879255126, rs879255125, rs879255127, rs751228587, rs879255128, rs879255130, rs369943481, rs879255131, rs879255132, rs879255133, rs879255134, rs112954220, rs776217028, rs879255135, rs879255136, rs879255138, rs879255139, rs879255140, rs879255141, rs879255142, rs879255144, rs879255145, rs879255146, rs879255147, rs879255153, rs879255155, rs879255156, rs879255157, rs879255158, rs879255159, rs879255160, rs879255161, rs879255163, rs879255164, rs370018159, rs879255166, rs879255167, rs879255168, rs879255169, rs879255172, rs879255174, rs763625913, rs879255175, rs879255176, rs879255177, rs879255178, rs879255181, rs879255185, rs879255186, rs879255188, rs879255187, rs767790696, rs879255193, rs879255194, rs879255196, rs879255197, rs879255198, rs879255200, rs879255202, rs879255204, rs773618064, rs879255207, rs879255209, rs879255210, rs879255212, rs879255213, rs879255215, rs879255217, rs747344293, rs879255218, rs879255219, rs879255222, rs377437226, rs879255224, rs879255227, rs879255229, rs1555803632, rs886039829, rs886039830, rs886039831, rs1057515537, rs774615547, rs1057516129, rs1057516132, rs1057516133, rs1057516135, rs777326720, rs751122998, rs1057516130, rs774069731, rs879254847, rs1057516134, rs867272973, rs1057516127, rs763147599, rs1057519647, rs1057519648, rs1057519649, rs1057519650, rs751317621, rs774016801, rs1057519652, rs1057519653, rs1057519654, rs1555803257, rs1057519655, rs879254601, rs1057519657, rs1057519662, rs879254618, rs1057519659, rs1057519660, rs1057519661, rs1057519663, rs1057519664, rs1057519665, rs1057519666, rs373869746, rs879254803, rs1057519668, rs1057519669, rs1057519670, rs1057519671, rs1057519672, rs1057519673, rs1057519674, rs879254993, rs1057519676, rs1057519679, rs1057519682, rs1057519683, rs1057519685, rs1057519687, rs1057519690, rs1060499931, rs1060499919, rs1064792905, rs1060499921, rs1060499922, rs1555805127, rs1060499923, rs1060499924, rs1060499926, rs1060499927, rs1555808044, rs1555808111, rs1060499930, rs770696696, rs1060500988, rs1060500987, rs879254637, rs1064794259, rs1555800611, rs1131692189, rs1555802312, rs1131692191, rs1131692192, rs1555803259, rs1131692193, rs1131692194, rs121908039, rs1131692195, rs1131692197, rs1131692198, rs148698650, rs1131692201, rs1131692202, rs879254715, rs370471092, rs1131692203, rs1131692204, rs1131692205, rs1131692206, rs1131692207, rs1131692208, rs1131692209, rs1131692210, rs1131692211, rs1131692214, rs1131692215, rs1131692217, rs1555806546, rs1131692219, rs879255095, rs1131692220, rs1131692221, rs200793488, rs1131692223, rs1131692224, rs1131692225, rs1131692226, rs1135402767, rs1555805507, rs1553137543, rs1382988295, rs1555802270, rs934496989, rs1555806455, rs1555807335, rs1555803481, rs1555804717, rs1372204035, rs1553135930, rs1057519691, rs1254346075, rs1553137693, rs1553137699, rs886046435, rs1553382295, rs1553382319, rs1553382325, rs1442815965, rs747606537, rs5742904, rs1553385404, rs1553385715, rs1555800620, rs1555800631, rs1555800632, rs1555800648, rs1555800724, rs1555802242, rs1555802245, rs1555802258, rs1555802287, rs200660051, rs1398808477, rs1555802822, rs752191968, rs1555803191, rs1555803213, rs879254529, rs754933794, rs1555803327, rs1555803337, rs1555803354, rs1013147010, rs1555803383, rs1555803391, rs753319170, rs1555803409, rs1555803432, rs1555803449, rs1555803641, rs1555803701, rs1555803837, rs1555803841, rs1555803879, rs1555803891, rs1555804443, rs1555804700, rs730882099, rs1225797407, rs879254871, rs1555805337, rs1555805348, rs1555805360, rs1555805380, rs1555805490, rs1555805530, rs1555805531, rs1555805985, rs1555806110, rs1555806448, rs1555806467, rs1555806582, rs778408161, rs1555807261, rs1555807390, rs1555807388, rs1555807421, rs1555807465, rs1555807475, rs1555808008, rs1555808107, rs1555808114, rs1555808118, rs1555808120, rs1555808139, rs875989942, rs1555809471, rs1555809490, rs1555809520, rs1555800701, rs762417023, rs1555802259, rs1555802291, rs1555803186, rs1555803254, rs1555803280, rs879254541, rs1555803455, rs1555803439, rs1555803471, rs1555803912, rs1555804467, rs1555804545, rs1555805947, rs879254992, rs1555807356, rs1555808143, rs1555805930, rs1201229554, rs1555806529, rs779921498, rs1555807206, rs753151497, rs1208216597, rs1555803908, rs1323416354, rs1555805409, rs1555805413, rs774467219, rs1555806088, rs1568600415, rs777903106, rs1568606711, rs1568610747, rs1568600459, rs1568592055, rs1568582652, rs1568591929, rs1568594903, rs1568600328, rs1600743301, rs750383461, rs1600683731, rs1600704961, rs1600715039, rs1600720921, rs1555804729, rs1600727337, rs1600727715, rs1600732894, rs1600726930, rs1600742966, rs1600762098, rs1600765031, rs1600715089, rs879255149, rs1600715567, rs1600732566, rs1257344396, rs1572802096, rs763778803, rs2044384127, rs2077272442, rs2077276411, rs2077276612, rs2077282480, rs2077297994, rs879254707, rs2077361078, rs2077408020, rs2077409930, rs2077412367, rs2077417709, rs2077419273, rs2077459772, rs2077475503, rs2077534881, rs762148512, rs140807148, rs2077460968, rs2077315885, rs2077271255	12730697, 23433573, 27998977, 26374825, 22683120, 24115837, 26036859, 24859021, 25962062, 21146822, 20006333, 17316651, 25014035, 28777095, 27206942, 18631360, 16183066, 23680767, 19081568, 27896130, 16909389, 24607922, 23375686, 18799458, 17765244, 18266662, 27280970, 24808179
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	28714975, 21378990, 29212778, 27135400, 30104761
Coronary heart disease	Coronary heart disease	rs-1	21347282
Myocardial infarction	Myocardial Infarction	rs12316150, rs41303970, rs909253, rs7291467, rs2234693
Hypertension	Hypertensive disease	rs13306026
Supravalvar aortic stenosis	Supravalvular aortic stenosis	rs-1, rs137854452, rs137854453, rs2132322943, rs1563826213, rs137854454, rs137854455, rs1554686162, rs397516433, rs727503783, rs727503782, rs727503022, rs727503023, rs727503024, rs727503026, rs727503027, rs727503028, rs727503029, rs727503031, rs727503033, rs727503034, rs727503035, rs727504419, rs727504433, rs727504434, rs727504581, rs730880355, rs863223518, rs863223520, rs200862792, rs878854452, rs886039351, rs1554669800, rs1554672602, rs1554672587, rs1554666513, rs1554669297, rs1554676454, rs1400530335, rs1563836689, rs1563793627, rs1583959262, rs1584494326, rs1583818183, rs1787875866, rs1791626037, rs1794096639, rs1794104889, rs199621188, rs1795205877, rs1797063858, rs782528759, rs1797218441, rs782674700
Nephroblastoma	Nephroblastoma	rs1553551874, rs1555913934, rs769116796	22544364
Hypobetalipoproteinemia	NON RARE IN EUROPE: Familial hypobetalipoproteinemia	rs281865425, rs397514255, rs121918383, rs121918384, rs121918385, rs-1, rs121918386, rs387906569, rs397514256, rs121918387, rs121918389, rs121918390, rs587776852, rs1572800245, rs606231236, rs797045253, rs143301836, rs1057518647, rs1553382678, rs756209187, rs759934326, rs1553383898, rs1553384177, rs1553384441, rs1553385404

Show/Hide Unknown Diseases (12)

Unknown
Disease name	Disease term	dbSNP ID	References
Arteriosclerosis	Premature arteriosclerosis
Cardiovascular diseases	Cardiovascular Diseases		30595370
Cerebral artery atherosclerosis	Cerebral artery atherosclerosis
Coronary aneurysm	Coronary Aneurysm
Coronary arteriosclerosis	Coronary Arteriosclerosis		27135400, 21378990
Fatty liver	Fatty Liver, Steatohepatitis
Homozygous hypercholesterolemia	Homozygous familial hypercholesterolemia
Hypocholesterolemia	Hypocholesterolemia
Peripheral arterial stenosis	Peripheral arterial stenosis
Renal artery stenosis	Renal Artery Stenosis
Renal steatosis	Renal steatosis
Xanthoma tendinosum	Xanthoma tendinosum

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