mutLBSgeneDB

mutLBSgeneDB
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 CDK8
Gene summary
Basic gene Info.Gene symbolCDK8
Gene namecyclin-dependent kinase 8
SynonymsK35
CytomapUCSC genome browser: 13q12
Type of geneprotein-coding
RefGenesNM_001260.1,
DescriptionCDK8 protein kinasecell division protein kinase 8mediator complex subunit CDK8mediator of RNA polymerase II transcription subunit CDK8protein kinase K35
Modification date20141207
dbXrefs MIM : 603184
HGNC : HGNC
Ensembl : ENSG00000132964
HPRD : 04422
Vega : OTTHUMG00000016617
ProteinUniProt: P49336
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_CDK8
BioGPS: 1024
PathwayNCI Pathway Interaction Database: CDK8
KEGG: CDK8
REACTOME: CDK8
Pathway Commons: CDK8
ContextiHOP: CDK8
ligand binding site mutation search in PubMed: CDK8
UCL Cancer Institute: CDK8
Assigned class in mutLBSgeneDBB: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID


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Ligand binding site mutations for CDK8
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
L142L142MBLCA1
Y32G30CBLCA1
S62A63TBLCA1
H149R150TBLCA1
E66E66QHNSC1
R65R65KHNSC1
S62S60PKIRC1
A172A172TLUAD1
D103D103NLUSC1
A155A155VLUSC1
L142H143YUCEC1
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.


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Protein structure related information for CDK8
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
Y32G30C0.12288439
L142L142M-1.3943511
A172A172T-1.1769443
H149R150T-0.78269261
A155A155V-0.60217376
E66E66Q-0.53160202
L142H143Y-0.47740735
S62A63T-0.38397395
S62S60P-0.25992384
D103D103N-0.21483268
R65R65K-0.18695682
(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 CDK8 from PDB

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Differential gene expression and gene-gene network for CDK8
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 CDK8 and the right PPI network was created from samples without mutations in the LBS of CDK8. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


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Phenotype information for CDK8
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type

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

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Pharmacological information for CDK8
Gene expression profile of anticancer drug treated cell-lines (CCLE)
Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient.

Gene-centered drug-gene interaction network
Drug information targeting mutLBSgene (Approved drugs only)
Drug statusDrugBank IDNameTypeDrug structure
Experimental|investigationalDB03496FlavopiridolSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of CDK8 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
0SWN-(2-PHENYLETHYL)QUINAZOLIN-4-AMINE4f7sAD103 A155
BAX4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE3rgfAE66 L142 H149 A172
0ST1-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]-3- [2-(MORPHOLIN-4-YL)ETHYL]UREA4f70AS62 R65 E66 H149 A172
4TV8-{3-CHLORO-5-[4-(1-METHYL-1H-PYRAZOL-4-YL) PHENYL]PYRIDIN-4-YL}-2,8-DIAZASPIRO[4.5]DECAN-1-ONE5bnjAY32 A172
C1ICORTISTATIN A4crlAY32 D103 A155
0SQ1-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]UREA4f6sAY32 S62 E66 H149 A172
0SSN-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]-4- [2-({[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5- YL]CARBAMOYL}AMINO)ETHYL]PIPERAZINE-1-CARBOXAMIDE4f6wAY32 S62 E66 H149 A172
0SOTERT-BUTYL [3-({[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H- PYRAZOL-5-YL]CARBAMOYL}AMINO)PROPYL]CARBAMATE4f7lAY32 S62 E66 H149 A172
0SR1-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]-3- [3-(MORPHOLIN-4-YL)PROPYL]UREA4f6uAY32 S62 R65 E66 H149 A172
0SU1-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]-3- (2-HYDROXYETHYL)UREA4f7jAY32 S62 R65 E66 H149 A172
0SV1-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]-3- (5-HYDROXYPENTYL)UREA4f7nAY32 S62 R65 E66 H149 A172


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Conservation information for LBS of CDK8
Multiple alignments for P49336 in multiple species
LBSAA sequence# speciesSpecies
A100LLFDYAEHDLW2Homo sapiens, Mus musculus
A100LLLDYAEHDLW1Caenorhabditis elegans
A100LLIDYAEHDLW1Drosophila melanogaster
A100LLFDFAEHDLW1Xenopus tropicalis
A155RDLKPANILVM4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
A155RDLKPANILLM1Caenorhabditis elegans
A172GRVKIADMGFA4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
A172GRVKIADLGFS1Caenorhabditis elegans
A50DDKDYALKQIE2Homo sapiens, Mus musculus
A50PNKEYALKMIE1Caenorhabditis elegans
A50DGKEYALKQID1Drosophila melanogaster
A50DDRDYALKQIE1Xenopus tropicalis
D103DYAEHDLWHII3Homo sapiens, Drosophila melanogaster, Mus musculus
D103DYAEHDLWHVI1Caenorhabditis elegans
D103DFAEHDLWHII1Xenopus tropicalis
D173RVKIADMGFAR4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
D173RVKIADLGFSR1Caenorhabditis elegans
D98VWLLFDYAEHD2Homo sapiens, Mus musculus
D98VWLLLDYAEHD1Caenorhabditis elegans
D98VFLLIDYAEHD1Drosophila melanogaster
D98VWLLFDFAEHD1Xenopus tropicalis
E101LFDYAEHDLWH2Homo sapiens, Mus musculus
E101LLDYAEHDLWH1Caenorhabditis elegans
E101LIDYAEHDLWH1Drosophila melanogaster
E101LFDFAEHDLWH1Xenopus tropicalis
E66MSACREIALLR4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
E66MSACREIALFR1Caenorhabditis elegans
F97KVWLLFDYAEH2Homo sapiens, Mus musculus
F97KVWLLLDYAEH1Caenorhabditis elegans
F97KVFLLIDYAEH1Drosophila melanogaster
F97KVWLLFDFAEH1Xenopus tropicalis
H106EHDLWHIIKFH4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
H106EHDLWHVIKHH1Caenorhabditis elegans
H149ANWVLHRDLKP3Homo sapiens, Xenopus tropicalis, Mus musculus
H149SNWVLHRDLKP2Caenorhabditis elegans, Drosophila melanogaster
I171RGRVKIADMGF4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
I171RGRVKIADLGF1Caenorhabditis elegans
I79KHPNVISLQKV2Homo sapiens, Xenopus tropicalis
I79RHPNLICLQRV1Caenorhabditis elegans
I79KHQNVITLIRV1Drosophila melanogaster
I79KHPNVISLLKV1Mus musculus
K52KDYALKQIEGT2Homo sapiens, Mus musculus
K52KEYALKMIEGQ1Caenorhabditis elegans
K52KEYALKQIDGT1Drosophila melanogaster
K52RDYALKQIEGT1Xenopus tropicalis
L142DGIHYLHANWV3Homo sapiens, Xenopus tropicalis, Mus musculus
L142SGMHYLHSNWV1Caenorhabditis elegans
L142DGIHYLHSNWV1Drosophila melanogaster
L158KPANILVMGEG3Homo sapiens, Xenopus tropicalis, Mus musculus
L158KPANILLMGDG1Caenorhabditis elegans
L158KPANILVMGDG1Drosophila melanogaster
L70REIALLRELKH4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
L70REIALFRELRH1Caenorhabditis elegans
L73ALLRELKHPNV3Homo sapiens, Xenopus tropicalis, Mus musculus
L73ALFRELRHPNL1Caenorhabditis elegans
L73ALLRELKHQNV1Drosophila melanogaster
M174VKIADMGFARL4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
M174VKIADLGFSRI1Caenorhabditis elegans
R356IPYPKREFLTE3Homo sapiens, Xenopus tropicalis, Mus musculus
R356IPYAKKEQQMT1Caenorhabditis elegans
R356IPYPKREFLTD1Drosophila melanogaster
R65SMSACREIALL4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
R65SMSACREIALF1Caenorhabditis elegans
S62TGISMSACREI3Homo sapiens, Xenopus tropicalis, Mus musculus
S62QGFSMSACREI1Caenorhabditis elegans
S62TGLSMSACREI1Drosophila melanogaster
V147LHANWVLHRDL3Homo sapiens, Xenopus tropicalis, Mus musculus
V147LHSNWVLHRDL2Caenorhabditis elegans, Drosophila melanogaster
V27EGCK-VGRGTY4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
V27ENSKEIGRGTY1Caenorhabditis elegans
V35GTYGHVYKA--4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
V35GTYGLVYKAVP1Caenorhabditis elegans
V78LKHPNVISLQK2Homo sapiens, Xenopus tropicalis
V78LRHPNLICLQR1Caenorhabditis elegans
V78LKHQNVITLIR1Drosophila melanogaster
V78LKHPNVISLLK1Mus musculus
W105AEHDLWHIIKF4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
W105AEHDLWHVIKH1Caenorhabditis elegans
Y32VGRGTYGHVYK4Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Mus musculus
Y32IGRGTYGLVYK1Caenorhabditis elegans
Y99WLLFDYAEHDL2Homo sapiens, Mus musculus
Y99WLLLDYAEHDL1Caenorhabditis elegans
Y99FLLIDYAEHDL1Drosophila melanogaster
Y99WLLFDFAEHDL1Xenopus tropicalis


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