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 GCK
Gene summary
Basic gene Info.Gene symbolGCK
Gene nameglucokinase (hexokinase 4)
SynonymsFGQTL3|GK|GLK|HHF3|HK4|HKIV|HXKP|LGLK|MODY2
CytomapUCSC genome browser: 7p15.3-p15.1
Type of geneprotein-coding
RefGenesNM_000162.3,
NM_033507.1,NM_033508.1,
DescriptionATP:D-hexose 6-phosphotransferaseHK IVglucokinasehexokinase D, pancreatic isozymehexokinase type IVhexokinase-4hexokinase-D
Modification date20141222
dbXrefs MIM : 138079
HGNC : HGNC
Ensembl : ENSG00000106633
HPRD : 00680
Vega : OTTHUMG00000022903
ProteinUniProt: P35557
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_GCK
BioGPS: 2645
PathwayNCI Pathway Interaction Database: GCK
KEGG: GCK
REACTOME: GCK
Pathway Commons: GCK
ContextiHOP: GCK
ligand binding site mutation search in PubMed: GCK
UCL Cancer Institute: GCK
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 GCK

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
Y215E216KSKCM2
Y215Y215FBRCA1
E256W257LLUSC1
R63R63HSKCM1
E221E221KSKCM1
H218D217NSKCM1
I159D160NSKCM1
T65T65ISKCM1
P66P66SSKCM1
D205D205NSKCM1
I159E157KSKCM1
G229G229DSKCM1
K12A10TSKCM1
T82F84LSTAD1
S336V338LUCEC1
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 GCK
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
I159D160N-1.8158925
I159E157K-1.3329433
H218D217N-1.1022584
Y215E216K-1.0871175
R63R63H-1.0815623
P66P66S-0.97816198
E221E221K-0.96841408
K12A10T-0.83154889
S336V338L-0.74761243
E256W257L-0.73226324
T65T65I-0.60187363
Y215Y215F-0.39522878
D205D205N-0.3839656
G229G229D-0.37144862
T82F84L-0.33049381
(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 GCK from PDB
PDB IDPDB titlePDB structure
1V4SCrystal structure of human glucokinase

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Differential gene expression and gene-gene network for GCK
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 GCK and the right PPI network was created from samples without mutations in the LBS of GCK. 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 GCK
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0011860Diabetes Mellitus, Type 2160Biomarker, GeneticVariation, Therapeutic
umls:C0342276Mason-Type Diabetes120Biomarker, GeneticVariation
umls:C0020456Hyperglycemia76Biomarker, GeneticVariation
umls:C0085207Diabetes, Gestational26Biomarker, GeneticVariation
umls:C0342277Diabetes Mellitus, Type Ii, Autosomal Dominant20Biomarker, GeneticVariation
umls:C2931834Congenital Hyperinsulinism15Biomarker, GeneticVariation
umls:C1833104Diabetes Mellitus, Permanent Neonatal9Biomarker, GeneticVariation
umls:C0011853Diabetes Mellitus, Experimental2Biomarker
umls:C0023893Liver Cirrhosis, Experimental1Biomarker

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs
44905E221KLikely pathogenicGermlineGeneReviews:NBK1447
MedGen:C1841962
OMIM:125851
Orphanet:ORPHA552

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Pharmacological information for GCK
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
ExperimentalDB02379Beta-D-GlucoseSmall molecule
ExperimentalDB073582-amino-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamideSmall molecule
ExperimentalDB073593-[(4-fluorophenyl)sulfanyl]-N-(4-methyl-1,3-thiazol-2-yl)-6-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carboxamideSmall molecule
ExperimentalDB081182-(methylamino)-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamideSmall molecule
ExperimentalDB082102-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDESmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of GCK go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
GLCALPHA-D-GLUCOSE3fr0AD205 E256
GLCALPHA-D-GLUCOSE3id8AD205 E256
GLCALPHA-D-GLUCOSE3imxAD205 E256
GLCALPHA-D-GLUCOSE4iseAD205 E256
GLCALPHA-D-GLUCOSE4isfAD205 E256
GLCALPHA-D-GLUCOSE4isgAD205 E256
GLCALPHA-D-GLUCOSE4mleAD205 E256
GLCALPHA-D-GLUCOSE4mlhAD205 E256
GLCALPHA-D-GLUCOSE4rchAD205 E256
GLCALPHA-D-GLUCOSE1v4sAD205 G229 E256
GLCALPHA-D-GLUCOSE3a0iXD205 G229 E256
GLCALPHA-D-GLUCOSE3f9mAD205 G229 E256
BGCBETA-D-GLUCOSE3fguAD205 G229 E256
GLCALPHA-D-GLUCOSE3goiAD205 G229 E256
GLCALPHA-D-GLUCOSE3h1vXD205 G229 E256
GLCALPHA-D-GLUCOSE3idhAD205 G229 E256
GLCALPHA-D-GLUCOSE3qicAD205 G229 E256
GLCALPHA-D-GLUCOSE3s41AD205 G229 E256
GLCALPHA-D-GLUCOSE3vevAD205 G229 E256
GLCALPHA-D-GLUCOSE3veyAD205 G229 E256
GLCALPHA-D-GLUCOSE3vf6AD205 G229 E256
GLCALPHA-D-GLUCOSE4dchAD205 G229 E256
GLCALPHA-D-GLUCOSE4dhyAD205 G229 E256
GLCALPHA-D-GLUCOSE4iwvAD205 G229 E256
GLCALPHA-D-GLUCOSE4ixcAD205 G229 E256
GLCALPHA-D-GLUCOSE4l3qAD205 G229 E256
GLCALPHA-D-GLUCOSE4no7AD205 G229 E256
ANPAMP-PNP3fguAD205 G229 S336
ANPAMP-PNP3id8AD205 G229 S336
1FW(2S)-3-CYCLOHEXYL-2-(6-FLUORO-4-OXOQUINAZOLIN-3(4H)- YL)-N-(1,3-THIAZOL-2-YL)PROPANAMIDE4iseAR63
3LZ1-{3-[(2-ETHYLPYRIDIN-3-YL)OXY]-5-(PYRIDIN-2- YLSULFANYL)PYRIDIN-2-YL}-3-METHYLUREA4rchAR63
LOI2-(METHYLAMINO)-N-(4-METHYL-1,3-THIAZOL-2-YL)-5-[(4-METHYL-4H-1,2,4-TRIAZOL-3-YL)SULFANYL]BENZAMIDE3goiAR63 H218
TK11-({5-[4-(METHYLSULFONYL)PHENOXY]-2-PYRIDIN-2-YL-1H-BENZIMIDAZOL-6-YL}METHYL)PYRROLIDINE-2,5-DIONE3h1vXR63 I159 Y215
S41N,N-DIMETHYL-5-({2-METHYL-6-[(5-METHYLPYRAZIN-2-YL)CARBAMOYL]-1-BENZOFURAN-4-YL}OXY)PYRIMIDINE-2-CARBOXAMIDE3s41AR63 I159 Y215 E221
S41N,N-DIMETHYL-5-({2-METHYL-6-[(5-METHYLPYRAZIN-2-YL)CARBAMOYL]-1-BENZOFURAN-4-YL}OXY)PYRIMIDINE-2-CARBOXAMIDE4dhyAR63 I159 Y215 E221
1FX(2S)-3-CYCLOHEXYL-2-(6-FLUORO-2,4-DIOXO-1,4- DIHYDROQUINAZOLIN-3(2H)-YL)-N-(1,3-THIAZOL-2-YL) PROPANAMIDE4isfAR63 P66
1FY(2S)-3-CYCLOHEXYL-2-[4-(METHYLSULFONYL)-2-OXOPIPERAZIN- 1-YL]-N-(1,3-THIAZOL-2-YL)PROPANAMIDE4isgAR63 P66
VO23-(BENZYLOXY)-5-METHYL-N-(4-METHYL-1,3-THIAZOL-2-YL) PYRIDIN-2-AMINE4mlhAR63 P66
0H4(2S)-3-CYCLOPENTYL-N-(5-METHYLPYRIDIN-2-YL)-2-[2-OXO-4-(TRIFLUOROMETHYL)PYRIDIN-1(2H)-YL]PROPANAMIDE3vevAR63 P66 I159 Y215
9266-{3-[(1-METHYL-1H-IMIDAZOL-2-YL) SULFANYL]PHENYL}PYRIDIN-2(1H)-ONE4l3qAR63 P66 I159 Y215 E221
B84(2R)-3-CYCLOPENTYL-N-(5-METHOXY[1,3]THIAZOLO[5,4-B]PYRIDIN-2-YL)-2-{4-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]PHENYL}PROPANAMIDE3imxAR63 P66 I159 Y215 H218
AJB2-AMINO-5-(4-METHYL-4H-[1,2,4]TRIAZOLE-3-YL-SULFANYL)-N-(4-METHYL-THIAZOLE-2-YL)BENZAMIDE3fr0AR63 P66 Y215
VO13-(BENZYLOXY)-N-(4-METHYL-1,3-THIAZOL-2-YL)PYRIDIN-2- AMINE4mleAR63 P66 Y215
AJI3-[(4-FLUOROPHENYL)THIO]-N-(4-METHYL-1,3-THIAZOL-2-YL)-6-[(4-METHYL-4H-1,2,4-TRIAZOL-3-YL)THIO]PYRIDINE-2-CARBOXAMIDE3a0iXR63 P66 Y215 E221
MRK2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE3id8AR63 P66 Y215 E221
0H66-({(2S)-3-CYCLOPENTYL-2-[4-(TRIFLUOROMETHYL)-1H-IMIDAZOL-1-YL]PROPANOYL}AMINO)PYRIDINE-3-CARBOXYLICACID3vf6AR63 T65 I159 Y215
2N8(2R)-2-[3-CHLORO-4-(METHYLSULFONYL)PHENYL]-3-[(1R)-3- OXOCYCLOPENTYL]-N-(PYRAZIN-2-YL)PROPANAMIDE4no7AR63 T65 I159 Y215 H218
4DC(2R)-3-CYCLOPENTYL-2-[4-(METHYLSULFONYL)PHENYL]-N-(1,3-THIAZOL-2-YL)PROPANAMIDE4dchAR63 T65 P66
1J9(2S)-2-{[1-(2-CHLOROPHENYL)-1H-PYRAZOLO[3,4- D]PYRIMIDIN-4-YL]OXY}-N-(5-CHLOROPYRIDIN-2-YL)-3-(2- HYDROXYETHOXY)PROPANAMIDE4iwvAR63 T65 P66 I159 Y215
1JD(2S)-2-{[1-(3-CHLOROPYRIDIN-2-YL)-1H-PYRAZOLO[3,4- D]PYRIMIDIN-4-YL]OXY}-N-(5-METHYLPYRIDIN-2-YL)-3- (PROPAN-2-YLOXY)PROPANAMIDE4ixcAR63 T65 P66 I159 Y215
MRK2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE3f9mAR63 T65 P66 Y215
MRK2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE1v4sAR63 T65 Y215
0H56-METHOXY-N-(1-METHYL-1H-PYRAZOL-3-YL)QUINAZOLIN-4-AMINE3veyAR63 T65 Y215
AGSADENOSINE 5'-[GAMMA-THIO]TRIPHOSPHATE3veyAT82 D205 G229 S336


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Conservation information for LBS of GCK
Multiple alignments for P35557 in multiple species
LBSAA sequence# speciesSpecies
A456LVSAVACKKAC3Homo sapiens, Mus musculus, Rattus norvegicus
C220YEDRQCEVGMI2Mus musculus, Rattus norvegicus
C220YEDHQCEVGMI1Homo sapiens
C230IVGTGCNACYM3Homo sapiens, Mus musculus, Rattus norvegicus
D205VAMVNDTVATM3Homo sapiens, Mus musculus, Rattus norvegicus
E221EDRQCEVGMIV2Mus musculus, Rattus norvegicus
E221EDHQCEVGMIV1Homo sapiens
E256MCVNTEWGAFG3Homo sapiens, Mus musculus, Rattus norvegicus
E290GQQLYEKIIGG2Mus musculus, Rattus norvegicus
E290GQQLYEKLIGG1Homo sapiens
E67VRSTPEGSEVG3Homo sapiens, Mus musculus, Rattus norvegicus
E70TPEGSEVGDFL3Homo sapiens, Mus musculus, Rattus norvegicus
E96VGEGEAGQWSV2Mus musculus, Rattus norvegicus
E96VGEGEEGQWSV1Homo sapiens
F152GFTFSFPVRHE3Homo sapiens, Mus musculus, Rattus norvegicus
G227VGMIVGTGCNA3Homo sapiens, Mus musculus, Rattus norvegicus
G229MIVGTGCNACY3Homo sapiens, Mus musculus, Rattus norvegicus
G295EKIIGGKYMGE2Mus musculus, Rattus norvegicus
G295EKLIGGKYMGE1Homo sapiens
G410TVGVDGSVYKL3Homo sapiens, Mus musculus, Rattus norvegicus
G68RSTPEGSEVGD3Homo sapiens, Mus musculus, Rattus norvegicus
G81SLDLGGTNFRV3Homo sapiens, Mus musculus, Rattus norvegicus
G97GEGEAGQWSVK2Mus musculus, Rattus norvegicus
G97GEGEEGQWSVK1Homo sapiens
H218CYYEDRQCEVG2Mus musculus, Rattus norvegicus
H218CYYEDHQCEVG1Homo sapiens
I159VRHEDIDKGIL2Homo sapiens, Mus musculus
I159VRHEDLDKGIL1Rattus norvegicus
I211TVATMISCYYE3Homo sapiens, Mus musculus, Rattus norvegicus
I225CEVGMIVGTGC3Homo sapiens, Mus musculus, Rattus norvegicus
K12RMEATKKEKVE2Mus musculus, Rattus norvegicus
K12RMEAAKKEKVE1Homo sapiens
K169LLNWTKGFKAS3Homo sapiens, Mus musculus, Rattus norvegicus
K296KIIGGKYMGEL2Mus musculus, Rattus norvegicus
K296KLIGGKYMGEL1Homo sapiens
K458SAVACKKACML3Homo sapiens, Mus musculus, Rattus norvegicus
K459AVACKKACMLG2Homo sapiens, Mus musculus
K459AVACKKACMLA1Rattus norvegicus
L415GSVYKLHPSFK3Homo sapiens, Mus musculus, Rattus norvegicus
L451GRGAALVSAVA3Homo sapiens, Mus musculus, Rattus norvegicus
M210DTVATMISCYY3Homo sapiens, Mus musculus, Rattus norvegicus
M235CNACYMEEMQN3Homo sapiens, Mus musculus, Rattus norvegicus
N204VVAMVNDTVAT3Homo sapiens, Mus musculus, Rattus norvegicus
N231VGTGCNACYME3Homo sapiens, Mus musculus, Rattus norvegicus
P153FTFSFPVRHED3Homo sapiens, Mus musculus, Rattus norvegicus
P66YVRSTPEGSEV3Homo sapiens, Mus musculus, Rattus norvegicus
Q287ANPGQQLYEKL1Homo sapiens
Q287VNPGQQLYEKI1Mus musculus
Q287ANPGQQLYEKI1Rattus norvegicus
Q98EGEAGQWSVKT2Mus musculus, Rattus norvegicus
Q98EGEEGQWSVKT1Homo sapiens
R333GAFETRFVSQV3Homo sapiens, Mus musculus, Rattus norvegicus
R63LPTYVRSTPEG3Homo sapiens, Mus musculus, Rattus norvegicus
S151LGFTFSFPVRH3Homo sapiens, Mus musculus, Rattus norvegicus
S336ETRFVSQVESD3Homo sapiens, Mus musculus, Rattus norvegicus
S411VGVDGSVYKLH3Homo sapiens, Mus musculus, Rattus norvegicus
S64PTYVRSTPEGS3Homo sapiens, Mus musculus, Rattus norvegicus
S69STPEGSEVGDF3Homo sapiens, Mus musculus, Rattus norvegicus
T168ILLNWTKGFKA3Homo sapiens, Mus musculus, Rattus norvegicus
T206AMVNDTVATMI3Homo sapiens, Mus musculus, Rattus norvegicus
T228GMIVGTGCNAC3Homo sapiens, Mus musculus, Rattus norvegicus
T332RGAFETRFVSQ3Homo sapiens, Mus musculus, Rattus norvegicus
T65TYVRSTPEGSE3Homo sapiens, Mus musculus, Rattus norvegicus
T82LDLGGTNFRVM3Homo sapiens, Mus musculus, Rattus norvegicus
V412GVDGSVYKLHP3Homo sapiens, Mus musculus, Rattus norvegicus
V452RGAALVSAVAC3Homo sapiens, Mus musculus, Rattus norvegicus
V455ALVSAVACKKA3Homo sapiens, Mus musculus, Rattus norvegicus
V62MLPTYVRSTPE3Homo sapiens, Mus musculus, Rattus norvegicus
W99GEAGQWSVKTK2Mus musculus, Rattus norvegicus
W99GEEGQWSVKTK1Homo sapiens
Y214TMISCYYEDRQ2Mus musculus, Rattus norvegicus
Y214TMISCYYEDHQ1Homo sapiens
Y215MISCYYEDRQC2Mus musculus, Rattus norvegicus
Y215MISCYYEDHQC1Homo sapiens
Y61KMLPTYVRSTP3Homo sapiens, Mus musculus, Rattus norvegicus


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