mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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Bioinformatics and Systems Medicine Laboratory Bioinformatics and Systems Medicine Laboratory

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 CYP2C8
Gene summary
Basic gene Info.Gene symbolCYP2C8
Gene namecytochrome P450, family 2, subfamily C, polypeptide 8
SynonymsCPC8|CYPIIC8|MP-12/MP-20
CytomapUCSC genome browser: 10q23.33
Type of geneprotein-coding
RefGenesNM_000770.3,
NM_001198853.1,NM_001198854.1,NM_001198855.1,NM_030878.1,
DescriptionP450 form 1cytochrome P450 2C8cytochrome P450 IIC2cytochrome P450 MP-12cytochrome P450 MP-20cytochrome P450 form 1cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 8flavoprotein-linked monooxygenasemicrosomal monooxygenases-
Modification date20141211
dbXrefs MIM : 601129
HGNC : HGNC
Ensembl : ENSG00000138115
HPRD : 03083
Vega : OTTHUMG00000018804
ProteinUniProt: P10632
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_CYP2C8
BioGPS: 1558
PathwayNCI Pathway Interaction Database: CYP2C8
KEGG: CYP2C8
REACTOME: CYP2C8
Pathway Commons: CYP2C8
ContextiHOP: CYP2C8
ligand binding site mutation search in PubMed: CYP2C8
UCL Cancer Institute: CYP2C8
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
GO:0006082organic acid metabolic process19651758
GO:0017144drug metabolic process19651758
GO:0042738exogenous drug catabolic process18619574
GO:0055114oxidation-reduction process19651758
GO:0070989oxidative demethylation18619574


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Ligand binding site mutations for CYP2C8

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
R433R433QCOAD2
L294D293NSKCM2
N217N218TCOAD1
R200K199ECOAD1
L131R132QGBM1
S114S115RGBM1
I476K474QHNSC1
A441A441VKIRC1
S429,R433G431RSKCM1
W120W120LSKCM1
V366V366MTHCA1
L361S359NUCEC1
R200R200IUCEC1
W120K118NUCEC1
I106R105IUCEC1
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 CYP2C8
Protein structure of wild type (WT) and mutant type (MT) of CYP2C8
Wild type CYP2C8
Mutant type CYP2C8

Free energy of binding of drugs to wild type and mutant tpye of CYP2C8
Gene symbolDrug nameFree energy of binding (kcal/mol) of wild typeFree energy of binding (kcal/mol) of mutant type
CYP2C8Gemfibrozil-7.5-7.5
CYP2C8Isoniazid-6.2-6.1
CYP2C8trimethoprim-6.6-6.8

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
L131R132Q-1.3456718
L294D293N-1.3114879
L361S359N-1.1741115
W120K118N-0.99578089
R200R200I-0.95379427
V366V366M-0.91650757
R433G431R-0.90540233
S429G431R-0.90540233
I106R105I-0.77591765
R200K199E-0.75316219
W120W120L-0.7385728
R433R433Q-0.5323139
S114S115R-0.35363227
N217N218T-0.27232615
I476K474Q-0.16625146
A441A441V-0.02172011
(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 CYP2C8 from PDB
PDB IDPDB titlePDB structure
1PQ2Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8

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Differential gene expression and gene-gene network for CYP2C8
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 CYP2C8 and the right PPI network was created from samples without mutations in the LBS of CYP2C8. 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 CYP2C8
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0022658Kidney Diseases1Biomarker
umls:C0027765Nervous System Diseases1Biomarker
umls:C1961102Precursor Cell Lymphoblastic Leukemia-Lymphoma1Biomarker
umls:C0035410Rhabdomyolysis1Biomarker

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

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Pharmacological information for CYP2C8
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
ApprovedDB00951IsoniazidSmall molecule
ExperimentalDB03796Palmitic AcidSmall molecule
ExperimentalDB08607(5R)-5-(4-{[(2R)-6-HYDROXY-2,5,7,8-TETRAMETHYL-3,4-DIHYDRO-2H-CHROMEN-2-YL]METHOXY}BENZYL)-1,3-THIAZOLIDINE-2,4-DIONESmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of CYP2C8 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
TDZTROGLITAZONE2vn0AI106 I476
MTKMONTELUKAST2nniAI106 S114 R200 N217 V366
REARETINOIC ACID2nnhAN217 I476
REARETINOIC ACID2nnhBN217 I476
REARETINOIC ACID2nnhAV366
REARETINOIC ACID2nnhBV366
225FELODIPINE2nnjAV366 I476
HEMHEME B1pq2AW120 L131 L294 L361 V366 S429 R433 A441
HEMHEME B2nniAW120 L131 L294 L361 V366 S429 R433 A441
HEMHEME B2vn0AW120 L131 L361 V366 S429 R433 A441
HEMHEME B1pq2BW120 L294 L361 V366 S429 R433 A441
HEMHEME B2nnhBW120 L294 L361 V366 S429 R433 A441
HEMHEME B2nnhAW120 L361 V366 S429 R433 A441
HEMHEME B2nnjAW120 L361 V366 S429 R433 A441


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Conservation information for LBS of CYP2C8
Multiple alignments for P10632 in multiple species
LBSAA sequence# speciesSpecies
A297NNLFAAGTETT2Mus musculus, Mus musculus
A297ADLFVAGTETT1Homo sapiens
A297MDLIGAGTETM1Rattus norvegicus
A297NDLFGAGTETT1Mus musculus
A436GKRICAGEGLA2Homo sapiens, Mus musculus
A436GKRVCAGEGLA2Mus musculus, Mus musculus
A436GKRACVGEGLA1Rattus norvegicus
A441AGEGLARMELF4Homo sapiens, Mus musculus, Mus musculus, Mus musculus
A441VGEGLARMQLF1Rattus norvegicus
C435AGKRVCAGEGL2Mus musculus, Mus musculus
C435AGKRICAGEGL1Homo sapiens
C435AGKRACVGEGL1Rattus norvegicus
C435TGKRICAGEGL1Mus musculus
E300FAAGTETTSTT2Mus musculus, Mus musculus
E300FVAGTETTSTT1Homo sapiens
E300IGAGTETMSTT1Rattus norvegicus
E300FGAGTETTSTT1Mus musculus
F201TLMKRFNENFR1Homo sapiens
F201TFMEKVNENLK1Rattus norvegicus
F201ILMDKINENVK1Mus musculus
F201MLMKKLNENVK1Mus musculus
F201MLMEKLNENVK1Mus musculus
F205KLNENVKILSS2Mus musculus, Mus musculus
F205RFNENFRILNS1Homo sapiens
F205KVNENLKIMSS1Rattus norvegicus
F205KINENVKILSS1Mus musculus
F428DYFMPFSAGKR1Homo sapiens
F428DYFLPFSAGKR1Rattus norvegicus
F428DYFMPFSTGKR1Mus musculus
F428DYFMTFSAGKR1Mus musculus
F428DHFMPFSAGKR1Mus musculus
G298NLFAAGTETTS2Mus musculus, Mus musculus
G298DLFVAGTETTS1Homo sapiens
G298DLIGAGTETMS1Rattus norvegicus
G298DLFGAGTETTS1Mus musculus
G365DLVPTGVPHAV1Homo sapiens
G365NFVPTNLPHAV1Rattus norvegicus
G365DLLPTSLPHAV1Mus musculus
G365NLVPNNLPHAV1Mus musculus
G365NLVPNNIPRAV1Mus musculus
G437KRICAGEGLAR2Homo sapiens, Mus musculus
G437KRVCAGEGLAR2Mus musculus, Mus musculus
G437KRACVGEGLAR1Rattus norvegicus
G98EFSGRGNSPIS1Homo sapiens
G98KFSGRGSYPMN1Rattus norvegicus
G98EFAGRGSFPMA1Mus musculus
G98EFSGRENIPMS1Mus musculus
G98EFSDRGSIPMV1Mus musculus
H368PTGVPHAVTTD1Homo sapiens
H368PTNLPHAVTCD1Rattus norvegicus
H368PTSLPHAVTCD1Mus musculus
H368PNNLPHAVTCD1Mus musculus
H368PNNIPRAVTCD1Mus musculus
I102RGNSPISQRIT1Homo sapiens
I102RGSYPMNENVT1Rattus norvegicus
I102RGSFPMAEKII1Mus musculus
I102RENIPMSEKIN1Mus musculus
I102RGSIPMVEKIN1Mus musculus
I106PISQRITKGLG1Homo sapiens
I106PMNENVTKGFG1Rattus norvegicus
I106PMAEKIIKGFG1Mus musculus
I106PMSEKINNGLG1Mus musculus
I106PMVEKINNGLG1Mus musculus
I112TKGLGIISSNG1Homo sapiens
I112TKGFGIVFSNG1Rattus norvegicus
I112IKGFGVVFSNG1Mus musculus
I112NNGLGITFSNG1Mus musculus
I112NNGLGIVFSNG1Mus musculus
I113KGLGIISSNGK1Homo sapiens
I113KGFGIVFSNGN1Rattus norvegicus
I113KGFGVVFSNGN1Mus musculus
I113NGLGITFSNGN1Mus musculus
I113NGLGIVFSNGN1Mus musculus
I178APCNVICSIIF3Mus musculus, Mus musculus, Mus musculus
I178APCNVICSVVF1Homo sapiens
I178APCNVICSITF1Rattus norvegicus
I213LSSPWLQVCNN2Mus musculus, Mus musculus
I213LNSPWIQVCNN1Homo sapiens
I213MSSPWMQVCNS1Rattus norvegicus
I213LSSPWLQVCNS1Mus musculus
I476AVTKGIVSLPP1Homo sapiens
I476PVLNGFASLPP1Rattus norvegicus
I476PVMNGFASLPP1Mus musculus
I476PFVNGLITLPP1Mus musculus
I476PFVNGLIALPP1Mus musculus
L131FTLMTLRNLGM2Mus musculus, Mus musculus
L131FSLTTLRNFGM1Homo sapiens
L131FTIMNFRNLGI1Rattus norvegicus
L131FTLTTLRNLGM1Mus musculus
L208ENVKILSSPWL3Mus musculus, Mus musculus, Mus musculus
L208ENFRILNSPWI1Homo sapiens
L208ENLKIMSSPWM1Rattus norvegicus
L294CTINNLFAAGT2Mus musculus, Mus musculus
L294GTVADLFVAGT1Homo sapiens
L294CSIMDLIGAGT1Rattus norvegicus
L294STINDLFGAGT1Mus musculus
L361QRYSDLVPTGV1Homo sapiens
L361QRFINFVPTNL1Rattus norvegicus
L361QRFIDLLPTSL1Mus musculus
L361QRFINLVPNNL1Mus musculus
L361QRFINLVPNNI1Mus musculus
L440CAGEGLARMEL4Homo sapiens, Mus musculus, Mus musculus, Mus musculus
L440CVGEGLARMQL1Rattus norvegicus
N204KRFNENFRILN1Homo sapiens
N204EKVNENLKIMS1Rattus norvegicus
N204DKINENVKILS1Mus musculus
N204KKLNENVKILS1Mus musculus
N204EKLNENVKILS1Mus musculus
N209NVKILSSPWLQ3Mus musculus, Mus musculus, Mus musculus
N209NFRILNSPWIQ1Homo sapiens
N209NLKIMSSPWMQ1Rattus norvegicus
N217WLQVCNNFPLL2Mus musculus, Mus musculus
N217WIQVCNNFPLL1Homo sapiens
N217WMQVCNSFPSL1Rattus norvegicus
N217WLQVCNSFPSL1Mus musculus
N236NKVLKNVALTR1Homo sapiens
N236HKIAKNINYMK1Rattus norvegicus
N236HKIVKNFNYLK1Mus musculus
N236HKVLKNFKYIR1Mus musculus
N236HKVLKNVKYIR1Mus musculus
N99FSGRGNSPISQ1Homo sapiens
N99FSGRGSYPMNE1Rattus norvegicus
N99FAGRGSFPMAE1Mus musculus
N99FSGRENIPMSE1Mus musculus
N99FSDRGSIPMVE1Mus musculus
P367VPTGVPHAVTT1Homo sapiens
P367VPTNLPHAVTC1Rattus norvegicus
P367LPTSLPHAVTC1Mus musculus
P367VPNNLPHAVTC1Mus musculus
P367VPNNIPRAVTC1Mus musculus
P427SDYFMPFSAGK1Homo sapiens
P427SDYFLPFSAGK1Rattus norvegicus
P427SDYFMPFSTGK1Mus musculus
P427SDYFMTFSAGK1Mus musculus
P427SDHFMPFSAGK1Mus musculus
Q356MIHEVQRFINL2Mus musculus, Mus musculus
Q356VVHEIQRYSDL1Homo sapiens
Q356MIHEVQRFINF1Rattus norvegicus
Q356MIHEVQRFIDL1Mus musculus
R124RWKEIRRFSLT1Homo sapiens
R124RWKEMRRFTIM1Rattus norvegicus
R124RWKEMRRFTLM1Mus musculus
R124SWKETRRFTLM1Mus musculus
R124RWKEIRRFTLT1Mus musculus
R200LTLMKRFNENF1Homo sapiens
R200LTFMEKVNENL1Rattus norvegicus
R200LILMDKINENV1Mus musculus
R200LMLMKKLNENV1Mus musculus
R200LMLMEKLNENV1Mus musculus
R241NVALTRSYIRE1Homo sapiens
R241NINYMKSYLLK1Rattus norvegicus
R241NFNYLKSYLLE1Mus musculus
R241NFKYIRSYLLE1Mus musculus
R241NVKYIRSYLLE1Mus musculus
R433FSAGKRVCAGE2Mus musculus, Mus musculus
R433FSAGKRICAGE1Homo sapiens
R433FSAGKRACVGE1Rattus norvegicus
R433FSTGKRICAGE1Mus musculus
R97EEFSGRGNSPI1Homo sapiens
R97EKFSGRGSYPM1Rattus norvegicus
R97EEFAGRGSFPM1Mus musculus
R97EEFSGRENIPM1Mus musculus
R97EEFSDRGSIPM1Mus musculus
S100SGRGNSPISQR1Homo sapiens
S100SGRGSYPMNEN1Rattus norvegicus
S100AGRGSFPMAEK1Mus musculus
S100SGRENIPMSEK1Mus musculus
S100SDRGSIPMVEK1Mus musculus
S103GNSPISQRITK1Homo sapiens
S103GSYPMNENVTK1Rattus norvegicus
S103GSFPMAEKIIK1Mus musculus
S103ENIPMSEKINN1Mus musculus
S103GSIPMVEKINN1Mus musculus
S114GLGIISSNGKR1Homo sapiens
S114GFGIVFSNGNR1Rattus norvegicus
S114GFGVVFSNGNR1Mus musculus
S114GLGITFSNGNS1Mus musculus
S114GLGIVFSNGNR1Mus musculus
S429YFMPFSAGKRI1Homo sapiens
S429YFLPFSAGKRA1Rattus norvegicus
S429YFMPFSTGKRI1Mus musculus
S429YFMTFSAGKRV1Mus musculus
S429HFMPFSAGKRV1Mus musculus
T107ISQRITKGLGI1Homo sapiens
T107MNENVTKGFGI1Rattus norvegicus
T107MAEKIIKGFGV1Mus musculus
T107MSEKINNGLGI1Mus musculus
T107MVEKINNGLGI1Mus musculus
T240KNVALTRSYIR1Homo sapiens
T240KNINYMKSYLL1Rattus norvegicus
T240KNFNYLKSYLL1Mus musculus
T240KNFKYIRSYLL1Mus musculus
T240KNVKYIRSYLL1Mus musculus
T301AAGTETTSTTL2Mus musculus, Mus musculus
T301VAGTETTSTTL1Homo sapiens
T301GAGTETMSTTL1Rattus norvegicus
T301GAGTETTSTTL1Mus musculus
T302AGTETTSTTLR4Homo sapiens, Mus musculus, Mus musculus, Mus musculus
T302AGTETMSTTLR1Rattus norvegicus
T305ETTSTTLRYAL3Mus musculus, Mus musculus, Mus musculus
T305ETTSTTLRYGL1Homo sapiens
T305ETMSTTLRYAL1Rattus norvegicus
V237KVLKNVALTRS1Homo sapiens
V237KIAKNINYMKS1Rattus norvegicus
V237KIVKNFNYLKS1Mus musculus
V237KVLKNFKYIRS1Mus musculus
V237KVLKNVKYIRS1Mus musculus
V296INNLFAAGTET2Mus musculus, Mus musculus
V296VADLFVAGTET1Homo sapiens
V296IMDLIGAGTET1Rattus norvegicus
V296INDLFGAGTET1Mus musculus
V362RYSDLVPTGVP1Homo sapiens
V362RFINFVPTNLP1Rattus norvegicus
V362RFIDLLPTSLP1Mus musculus
V362RFINLVPNNLP1Mus musculus
V362RFINLVPNNIP1Mus musculus
V366LVPTGVPHAVT1Homo sapiens
V366FVPTNLPHAVT1Rattus norvegicus
V366LLPTSLPHAVT1Mus musculus
V366LVPNNLPHAVT1Mus musculus
V366LVPNNIPRAVT1Mus musculus
V477VTKGIVSLPPS1Homo sapiens
V477VLNGFASLPPT1Rattus norvegicus
V477VMNGFASLPPP1Mus musculus
V477FVNGLITLPPH1Mus musculus
V477FVNGLIALPPH1Mus musculus
W120SNGNRWKEMRR2Rattus norvegicus, Mus musculus
W120SNGKRWKEIRR1Homo sapiens
W120SNGNSWKETRR1Mus musculus
W120SNGNRWKEIRR1Mus musculus


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