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 TTK
Gene summary
Basic gene Info.Gene symbolTTK
Gene nameTTK protein kinase
SynonymsCT96|ESK|MPH1|MPS1|MPS1L1|PYT
CytomapUCSC genome browser: 6q14.1
Type of geneprotein-coding
RefGenesNM_001166691.1,
NM_003318.4,
Descriptioncancer/testis antigen 96dual specificity protein kinase TTKmonopolar spindle 1 kinasemonopolar spindle 1-like 1phosphotyrosine picked threonine kinasephosphotyrosine picked threonine-protein kinase
Modification date20141222
dbXrefs MIM : 604092
HGNC : HGNC
Ensembl : ENSG00000112742
HPRD : 04973
Vega : OTTHUMG00000015088
ProteinUniProt: P33981
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_TTK
BioGPS: 7272
PathwayNCI Pathway Interaction Database: TTK
KEGG: TTK
REACTOME: TTK
Pathway Commons: TTK
ContextiHOP: TTK
ligand binding site mutation search in PubMed: TTK
UCL Cancer Institute: TTK
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 TTK
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
M600M600ICOAD2
L654L654VBLCA1
D664G666EBRCA1
I586R587QCOAD1
E571E571KCOAD1
L575,E571A573VCOAD1
D664G666RGBM1
G534G534EGBM1
P673T675KKIRC1
C604C604FLUAD1
L575L575WLUAD1
L575L575FLUAD1
Y568D566GLUSC1
M602,M600V601IUCEC1
Q541,V539F540LUCEC1
E571E571KUCEC1
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 TTK
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
G534G534E0.67471639
I586R587Q-1.5168686
L654L654V-1.356538
P673T675K-1.3051448
C604C604F-1.1809374
Y568D566G-0.98581645
E571E571K-0.89950978
L575L575F-0.84477559
M600M600I-0.82235035
L575L575W-0.78164485
L575A573V-0.76456557
E571A573V-0.76456557
M600V601I-0.76127658
M602V601I-0.76127658
D664G666R-0.7130311
D664G666E-0.65406249
V539F540L-0.051810988
Q541F540L-0.051810988
(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 TTK from PDB
PDB IDPDB titlePDB structure
3CEKCrystal structure of human dual specificity protein kinase (TTK)

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Differential gene expression and gene-gene network for TTK
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 TTK and the right PPI network was created from samples without mutations in the LBS of TTK. 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 TTK
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0017661Glomerulonephritis, IGA1Biomarker
umls:C0032460Polycystic Ovary Syndrome1Biomarker

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

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Pharmacological information for TTK
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
ExperimentalDB017822,6-Dihydroanthra/1,9-Cd/Pyrazol-6-OneSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of TTK go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
PWUISOPROPYL 6-((4-(1,2-DIMETHYL-1H-IMIDAZOL-5- YL)PHENYL)AMINO)-2-(1-METHYL-1H-PYRAZOL-4-YL)- 1H-PYRROLO[3,2-C]PYRIDINE-1-CARBOXYLATE5ap2AE571 I586 M602 C604 L654 P673
2QKN-[(1R)-1-(2-CHLOROPHENYL)PROPYL]-3-{4-[(1- METHYLPIPERIDIN-4-YL)OXY]PHENYL}-1H-INDAZOLE-5- CARBOXAMIDE4o6lBG534 V539 I586 M602 C604 L654 D664
ATPATP3hmnAG534 V539 M602 L654
SVEN-(2,6-DIETHYLPHENYL)-1-METHYL-8-({4-[(1-METHYLPIPERIDIN-4-YL)CARBAMOYL]-2-(TRIFLUOROMETHOXY)PHENYL}AMINO)-4,5-DIHYDRO-1H-PYRAZOLH]QUINAZOLINE-3-CARBOXAMIDE2x9eAG534 V539 Q541 I586 C604 L654 D664
1PH2-PHENYL-N-[3-(3-SULFAMOYLPHENYL)-2H-INDAZOL-5- YL]ACETAMIDE4jt3AG534 V539 Q541 M602 C604 L654
ZO6THIENO[3,2-C][2,6]NAPHTHYRIDINE4bi1AI586 C604 L654
Z0BTHIENO[2,3-C][2,6]NAPHTHYRIDINE4bhzAI586 L654
Z0W5H-PYRIMIDO[5,4-B]INDOLE4bi0AI586 L654
5372,6-DIHYDROANTHRA/1,9-CD/PYRAZOL-6-ONE2zmdAI586 M602 C604 L654
ZO8THIENO[2,3-C][2,7]NAPHTHYRIDINE4bi2AI586 M602 L654
4T9N-(3,4-DIMETHOXYPHENYL)-2-(1H-PYRAZOL-4-YL)- 1H-PYRROLO[3,2-C]PYRIDIN-6-AMINEETHYL METHYL (4R)-4-(2,3-DICHLOROPHENYL)-2,6- DIMETHYL-1,4-DIHYDROPYRIDINE-3,5- DICARBOXYLATE4c4eAI586 M602 L654
7ROTERT-BUTYL 6-((2-CHLORO-4-(DIMETHYLCARBAMOYL) PHENYL)AMINO)-2-(1-METHYL-1H-PYRAZOL-4-YL)- 1H-PYRROLO[3,2-C]PYRIDINE-1-CARBOXYLATE4c4gAL575 I586 M602 C604 L654
3D73-AMINO-5-(1-METHYL-1H-PYRAZOL-4-YL)PYRIDIN- 2(1H)-ONE4cv8AM602 C604 L654
WBIN-(6-OXO-1,6-DIHYDRO-3,4'-BIPYRIDIN-5-YL)-4- (PIPERIDIN-1-YL)BENZAMIDE4cvaAM602 C604 L654
CX47-CHLORO-N-(CYCLOPROPYLMETHYL)QUINAZOLIN-4-AMINE3hmpAQ541 I586 M602 C604 L654
7CEN-(2-METHOXYPHENYL)-2-(1,3-OXAZOL-5-YL)-1H- PYRROLO[3,2-C]PYRIDIN-6-AMINE4c4fAQ541 I586 M602 C604 L654
92M9-CYCLOPENTYL-2-{[4-(4-HYDROXYPIPERIDIN-1-YL)-2-METHOXYPHENYL]AMINO}-5-METHYL-5,7,8,9-TETRAHYDRO-6H-PYRIMIDO[4,5-B][1,4]DIAZEPIN-6-ONE3h9fAQ541 I586 M602 C604 L654 D664
S221-(4-(4-(2-(ISOPROPYLSULFONYL)PHENYLAMINO)-1H-PYRROLO[2,3-B]PYRIDIN-6-YLAMINO)-3-METHOXYPHENYL)PIPERIDIN-4-OL3gfwAQ541 M602 C604 L654
STUSTAUROSPORINE3hmoAV539 C604 L654
DYKN-{2-METHOXY-4-[(1-METHYLPIPERIDIN-4-YL)OXY] PHENYL}-4-(1H-PYRROLO[2,3-C]PYRIDIN-3-YL) PYRIMIDIN-2-AMINE4d2sAV539 C604 L654
AU59-CYCLOPENTYL-2-[[2-METHOXY-4-[(1- METHYLPIPERIDIN-4-YL)OXY]-PHENYL]AMINO]-7-METHYL-7,9- DIHYDRO-8H-PURIN-8-ONE5ap0AV539 I586 M602 C604 L654
7ROTERT-BUTYL 6-((2-CHLORO-4-(DIMETHYLCARBAMOYL) PHENYL)AMINO)-2-(1-METHYL-1H-PYRAZOL-4-YL)- 1H-PYRROLO[3,2-C]PYRIDINE-1-CARBOXYLATE5ap5AV539 I586 M602 C604 L654
2QKN-[(1R)-1-(2-CHLOROPHENYL)PROPYL]-3-{4-[(1- METHYLPIPERIDIN-4-YL)OXY]PHENYL}-1H-INDAZOLE-5- CARBOXAMIDE4o6lAV539 I586 M602 C604 L654 D664 P673
1PF4-(CYCLOHEXYLMETHOXY)-3-{4-[(1-METHYLPIPERIDIN-4-YL) OXY]PHENYL}-2H-INDAZOLE4js8AV539 I586 M602 C604 L654 P673
PWUISOPROPYL 6-((4-(1,2-DIMETHYL-1H-IMIDAZOL-5-YL)PHENYL) AMINO)-2-(1-METHYL-1H-PYRAZOL-4-YL)-1H-PYRROLO[3,2- C]PYRIDINE-1-CARBOXYLATE5ap6AV539 I586 M602 L654 P673
O224-[(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL) AMINO]BENZAMIDE3vquAV539 M602 C604 L654 P673
O434-{6-(CYCLOHEXYLAMINO)-8-[(TETRAHYDRO-2H-PYRAN-4- YLMETHYL)AMINO]IMIDAZO[1,2-B]PYRIDAZIN-3-YL}-N- CYCLOPROPYLBENZAMIDE3wzjAV539 Q541 E571 L575 M600 M602 C604 L654 D664 P673
1O55-[5-ETHOXY-6-(1-METHYL-1H-PYRAZOL-4-YL)-1H-INDAZOL-3- YL]-2-METHYLBENZENESULFONAMIDE3w1fAV539 Q541 E571 L575 M602 C604 L654
O23N-CYCLOPROPYL-4-{8-[(THIOPHEN-2-YLMETHYL) AMINO]IMIDAZO[1,2-A]PYRAZIN-3-YL}BENZAMIDE3wzkAV539 Q541 E571 M602 C604 L654 D664
X21TERT-BUTYL 6-{[2-CHLORO-4-(1-METHYL-1H- IMIDAZOL-5-YL)PHENYL]AMINO}-2-(1-METHYL-1H-PYRAZOL- 4-YL)-1H-PYRROLO[3,2-C]PYRIDINE-1- CARBOXYLATE4c4jAV539 Q541 E571 M602 C604 L654 P673
X20TERT-BUTYL 6-{[2-CHLORO-4-(DIMETHYLCARBAMOYL) PHENYL]AMINO}-2-(1,3-OXAZOL-5-YL)-1H- PYRROLO[3,2-C]PYRIDINE-1-CARBOXYLATE4c4iAV539 Q541 I586 M602 C604 L654
O386-{[3-(CYANOMETHOXY)-4-(1-METHYL-1H-PYRAZOL-4-YL) PHENYL]AMINO}-2-(CYCLOHEXYLAMINO)PYRIDINE-3- CARBONITRILE3wyxAV539 Q541 I586 M602 C604 L654
AU59-CYCLOPENTYL-2-[[2-METHOXY-4-[(1- METHYLPIPERIDIN-4-YL)OXY]-PHENYL]AMINO]-7-METHYL-7,9- DIHYDRO-8H-PURIN-8-ONE5ap3AV539 Q541 I586 M602 C604 L654
O386-{[3-(CYANOMETHOXY)-4-(1-METHYL-1H-PYRAZOL- 4-YL)PHENYL]AMINO}-2-(CYCLOHEXYLAMINO) PYRIDINE-3-CARBONITRILE5ap1AV539 Q541 I586 M602 C604 L654 P673
O386-{[3-(CYANOMETHOXY)-4-(1-METHYL-1H-PYRAZOL- 4-YL)PHENYL]AMINO}-2-(CYCLOHEXYLAMINO) PYRIDINE-3-CARBONITRILE5ap4AV539 Q541 I586 M602 C604 L654 P673
SVEN-(2,6-DIETHYLPHENYL)-1-METHYL-8-({4-[(1-METHYLPIPERIDIN-4-YL)CARBAMOYL]-2-(TRIFLUOROMETHOXY)PHENYL}AMINO)-4,5-DIHYDRO-1H-PYRAZOLH]QUINAZOLINE-3-CARBOXAMIDE5ap7AV539 Q541 I586 M602 L654 D664
7ROTERT-BUTYL 6-((2-CHLORO-4-(DIMETHYLCARBAMOYL) PHENYL)AMINO)-2-(1-METHYL-1H-PYRAZOL-4-YL)- 1H-PYRROLO[3,2-C]PYRIDINE-1-CARBOXYLATE4c4hAV539 Q541 M602 C604 L654
O17(2E)-3-[4-({4-AMINO-5-CYANO-6-[(3S,5S,7S)- TRICYCLO[3.3.1.1~3,7~]DEC-1-YLAMINO]PYRIDIN-2- YL}AMINO)-2-(CYANOMETHOXY)PHENYL]-N-(2-METHOXYETHYL) PROP-2-ENAMIDE3wyyAV539 Q541 M602 C604 L654 P673
1KAPOLYETHYLENE GLYCOL FRAGMENT(2-HYDROXYETHOXY)ACETALDEHYDE5ap5AY568 E571


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Conservation information for LBS of TTK
Multiple alignments for P33981 in multiple species
LBSAA sequence# speciesSpecies


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