mutated Ligand Binding Site gene DataBase





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Gene Summary

Ligand Binding Site Mutation Information

Protein Structure Related Information

Gene Expression and Gene-Gene Network

Phenotype Information

Pharmacological Information

Conservation Information for LBS

Gene summary for PCSK9
Gene summary
Basic gene Info.Gene symbolPCSK9
Gene nameproprotein convertase subtilisin/kexin type 9
CytomapUCSC genome browser: 1p32.3
Type of geneprotein-coding
Descriptionconvertase subtilisin/kexin type 9 preproproteinneural apoptosis regulated convertase 1subtilisin/kexin-like protease PC9
Modification date20141222
dbXrefs MIM : 607786
Ensembl : ENSG00000169174
HPRD : 07080
Vega : OTTHUMG00000008136
ProteinUniProt: Q8NBP7
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PCSK9
BioGPS: 255738
PathwayNCI Pathway Interaction Database: PCSK9
Pathway Commons: PCSK9
ContextiHOP: PCSK9
ligand binding site mutation search in PubMed: PCSK9
UCL Cancer Institute: PCSK9
Assigned class in mutLBSgeneDBA: This gene has a literature evidence and it belongs to targetable_mutLBSgenes.
References showing study about ligand binding site mutation for PCSK9.1. Kwon, H. J., Lagace, T. A., McNutt, M. C., Horton, J. D., & Deisenhofer, J. (2008). Molecular basis for LDL receptor recognition by PCSK9. Proceedings of the National Academy of Sciences, 105(6), 1820-1825. 18250299

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO:0001920negative regulation of receptor recycling17452316
GO:0002092positive regulation of receptor internalization17328821
GO:0007041lysosomal transport17452316
GO:0010469regulation of receptor activity17328821
GO:0010989negative regulation of low-density lipoprotein particle clearance17328821
GO:0016540protein autoprocessing14622975
GO:0032802low-density lipoprotein particle receptor catabolic process16912035

Ligand binding site mutations for PCSK9
Lollipop-style diagram of mutations at LBS in amino-acid sequence.
We represented ligand binding site mutations only. (You can see big image via clicking.)
: non-synonymous mutation on LBS, Circle size denotes number of samples.

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma.

Protein structure related information for PCSK9
Relative protein structure stability change (ΔΔE) using Mupro 1.1
Mupro score denotes assessment of the effect of mutations on thermodynamic stability.
  (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability)
: nsSNV at non-LBS: nsSNV at LBS

nsSNVs sorted by the relative stability change of protein structure by each mutation
Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene.
LBSAAchange of nsSNVRelative stability change
(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132)

Structure image for PCSK9 from PDB

Differential gene expression and gene-gene network for PCSK9
Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

Differential co-expressed gene network based on protein-protein interaction data (CePIN)
* Left PPI network was created from samples with mutations in the LBS of PCSK9 and the right PPI network was created from samples without mutations in the LBS of PCSK9. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


Phenotype information for PCSK9
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0020443Hypercholesterolemia49Biomarker, GeneticVariation
umls:C1956346Coronary Artery Disease13Biomarker, GeneticVariation
umls:C1863551Hypercholesterolemia, Autosomal Dominant, 32Biomarker, GeneticVariation

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

Pharmacological information for PCSK9

Gene-centered drug-gene interaction network
Drug information targeting mutLBSgene (Approved drugs only)
Drug statusDrugBank IDNameTypeDrug structure

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PCSK9 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
CACALCIUM(2+)2qtwBA328 A330
CACALCIUM(2+)2w2mAA328 A330
CACALCIUM(2+)2w2nAA328 A330
CACALCIUM(2+)2w2qAA328 A330
CACALCIUM(2+)3p5bAA328 A330
CACALCIUM(2+)3p5cAA328 A330

Conservation information for LBS of PCSK9
Multiple alignments for Q8NBP7 in multiple species
LBSAA sequence# speciesSpecies
A239VSGRDAGVAKG5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
A239IGSKHFGVAKN1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
A239IAGKTFGVSKN1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
A328CLYSPASAPEV5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
A328CLSSPAGAEKS1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
A328CGTSPARVSNA1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
A330YSPASAPEVIT5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
A330SSPAGAEKSIT1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
A330TSPARVSNAMT1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
C358TNFGRCVDLFA5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
C358SNWGTCVDVFA1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
C358SNIGSCVDIFA1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
C375GASSDCSTCFV3Homo sapiens, Macaca mulatta, Pan troglodytes
C375GASSDCSTCFM1Mus musculus
C375GASSDCSTCYM1Rattus norvegicus
C375STYIGSRNATL1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
C375SDWIGSNRASM1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
C378SDCSTCFVSQS2Homo sapiens, Pan troglodytes
C378SDCSTCFVSRS1Macaca mulatta
C378SDCSTCFMSQS1Mus musculus
C378SDCSTCYMSQS1Rattus norvegicus
C378IGSRNATLSLS1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
C378IGSNRASMILS1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D238VVSGRDAGVAK5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
D238IIGSKHFGVAK1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D238TIAGKTFGVSK1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D360FGRCVDLFAPG5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
D360WGTCVDVFAPG1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D360IGSCVDIFAPG1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D374IGASSDCSTCF4Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus
D374IGASSDCSTCY1Rattus norvegicus
D374MSTYIGSRNAT1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D374LSDWIGSNRAS1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F379DCSTCFVSQSG2Homo sapiens, Pan troglodytes
F379DCSTCFVSRSG1Macaca mulatta
F379DCSTCFMSQSG1Mus musculus
F379DCSTCYMSQSG1Rattus norvegicus
F379GSRNATLSLSG1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
F379GSNRASMILSG1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
H557CHQQGHVLTGC3Homo sapiens, Macaca mulatta, Pan troglodytes
H557CHQKDHVLTGC2Mus musculus, Rattus norvegicus
H557-----------2Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843)
H602HASCCHAPGLE3Homo sapiens, Macaca mulatta, Rattus norvegicus
H602-----------2Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843)
H602HASCCRAPGLE1Pan troglodytes
H602YASCCHAPGLE1Mus musculus
I369PGEDIIGASSD3Homo sapiens, Macaca mulatta, Pan troglodytes
I369PGKDIIGASSD2Mus musculus, Rattus norvegicus
I369PGINIMSTYIG1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
I369PGSLILSDWIG1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
I416LRQRLIHFSAK3Homo sapiens, Macaca mulatta, Pan troglodytes
I416LRQRLIHFSTK1Mus musculus
I416LRQRLILFSTK1Rattus norvegicus
I416LKEKVLKFSTQ1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
I416LKKYMLKFALK1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K125PGFLVKMSGDL3Homo sapiens, Macaca mulatta, Pan troglodytes
K125PGFLVKMSSDL2Mus musculus, Rattus norvegicus
K125RGYTGYFTDEI1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K125LGYAGRFSPWL1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L108ARRGYLTKILH3Homo sapiens, Macaca mulatta, Pan troglodytes
L108ARRGYVIKVLH2Mus musculus, Rattus norvegicus
L108STSVGKLTEND1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L108EKRSLDFKDVS1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L440VLTPNLVAALP3Homo sapiens, Macaca mulatta, Pan troglodytes
L440VLTPNLVATLP1Mus musculus
L440VLTPNRVATLP1Rattus norvegicus
L440--TPNKLI---1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L440--TPNVLA---1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
M126GFLVKMSGDLL3Homo sapiens, Macaca mulatta, Pan troglodytes
M126GFLVKMSSDLL2Mus musculus, Rattus norvegicus
M126GYTGYFTDEII1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
M126GYAGRFSPWLV1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
P155-AQSIPWNLER5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
P155LQEEAPWGLHR1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
P155-QTFAPWGLAR1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
P331SPASAPEVITV5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
P331SPAGAEKSITV1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
P331SPARVSNAMTV1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Q413LAELRQRLIHF4Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus
Q413LAELRQRLILF1Rattus norvegicus
Q413PQELKEKVLKF1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Q413PVELKKYMLKF1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
R194IQSDHREIEGR3Homo sapiens, Macaca mulatta, Pan troglodytes
R194IQGAHREIEGR1Mus musculus
R194IQSGHREIEGR1Rattus norvegicus
R194IDTEHEDFEGR1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
R194INIEHQDFQGR1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
R412TLAELRQRLIH4Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus
R412TLAELRQRLIL1Rattus norvegicus
R412SPQELKEKVLK1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
R412HPVELKKYMLK1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S153---AQSIPWNL5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
S153SSLQEEAPWGL1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S153E--QTFAPWGL1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S372DIIGASSDCST5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
S372NIMSTYIGSRN1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S372LILSDWIGSNR1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
T335APEVITVGATN5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
T335AEKSITVGAST1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
T335VSNAMTVGAST1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
T377SSDCSTCFVSQ2Homo sapiens, Pan troglodytes
T377SSDCSTCFVSR1Macaca mulatta
T377SSDCSTCFMSQ1Mus musculus
T377SSDCSTCYMSQ1Rattus norvegicus
T377YIGSRNATLSL1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
T377WIGSNRASMIL1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V333ASAPEVITVGA5Homo sapiens, Macaca mulatta, Pan troglodytes, Mus musculus, Rattus norvegicus
V333AGAEKSITVGA1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V333ARVSNAMTVGA1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V380CSTCFVSQSGT2Homo sapiens, Pan troglodytes
V380CSTCFVSRSGT1Macaca mulatta
V380CSTCFMSQSGT1Mus musculus
V380CSTCYMSQSGT1Rattus norvegicus
V380SRNATLSLSGT1Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V380SNRASMILSGT1Schizosaccharomyces pombe (strain 972 / ATCC 24843)

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