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 TLR4
Gene summary
Basic gene Info.Gene symbolTLR4
Gene nametoll-like receptor 4
SynonymsARMD10|CD284|TLR-4|TOLL
CytomapUCSC genome browser: 9q33.1
Type of geneprotein-coding
RefGenesNM_003266.3,
NM_138554.4,NM_138557.2,NM_138556.1,
DescriptionhTollhomolog of Drosophila toll
Modification date20141222
dbXrefs MIM : 603030
HGNC : HGNC
Ensembl : ENSG00000136869
HPRD : 04325
Vega : OTTHUMG00000021046
ProteinUniProt: O00206
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_TLR4
BioGPS: 7099
PathwayNCI Pathway Interaction Database: TLR4
KEGG: TLR4
REACTOME: TLR4
Pathway Commons: TLR4
ContextiHOP: TLR4
ligand binding site mutation search in PubMed: TLR4
UCL Cancer Institute: TLR4
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 TLR4.1. "Kiyokawa T, Akashi-Takamura S, Shibata T, Matsumoto F, Nishitani C, Kuroki Y, Seto Y, Miyake K. A single base mutation in the PRAT4A gene reveals differential interaction of PRAT4A with Toll-like receptors. Int Immunol. 2008 Nov;20(11):1407-15. doi: 10.1093/intimm/dxn098. Epub 2008 Sep 9." 18780723

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0007252I-kappaB phosphorylation19740627
GO:0031663lipopolysaccharide-mediated signaling pathway10880523
GO:0032496response to lipopolysaccharide12594207
GO:0032497detection of lipopolysaccharide19252480
GO:0032722positive regulation of chemokine production19740627
GO:0032755positive regulation of interleukin-6 production19740627
GO:0032757positive regulation of interleukin-8 production19740627
GO:0042346positive regulation of NF-kappaB import into nucleus19740627
GO:0042535positive regulation of tumor necrosis factor biosynthetic process17951129
GO:0045084positive regulation of interleukin-12 biosynthetic process15027902
GO:0045416positive regulation of interleukin-8 biosynthetic process17951129
GO:0051092positive regulation of NF-kappaB transcription factor activity12594207


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Ligand binding site mutations for TLR4
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
N526V524EBRCA1
K150K150NCOAD1
S552N554SCOAD1
E31V30MHNSC1
N575,T577L576IHNSC1
P53P53HHNSC1
S504S504CHNSC1
P13A14SLUAD1
S415S415ILUAD1
E31V33FLUAD1
P53F54CLUSC1
S415T413SLUSC1
Y38C40FOV1
E439E439KSKCM1
N526N526YSKCM1
V602E603KSKCM1
Q436M437ISKCM1
S504D502NSKCM1
F440F440LSTAD1
Q436Q436RSTAD1
F440F440VSTAD1
S504S504PSTAD1
E439E439ASTAD1
E439E439VSTAD1
D550L549IUCEC1
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 TLR4
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
P13A14S-1.2466319
E31V33F-1.2309192
P53P53H-1.2205236
E439E439A-1.14058
F440F440V-1.0675783
P53F54C-1.0569701
E439E439K-1.0248895
V602E603K-1.0079439
N526V524E-1.006044
S415T413S-0.97453449
Q436M437I-0.93791527
Y38C40F-0.92334959
T577L576I-0.90700499
N575L576I-0.90700499
S552N554S-0.88775389
F440F440L-0.85921703
S504S504P-0.80692506
E31V30M-0.78532804
Q436Q436R-0.77936716
D550L549I-0.76197932
S504S504C-0.75133254
E439E439V-0.69282848
S504D502N-0.55162051
N526N526Y-0.51719072
K150K150N-0.44157795
S415S415I-0.29747249
(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 TLR4 from PDB

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Differential gene expression and gene-gene network for TLR4
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 TLR4 and the right PPI network was created from samples without mutations in the LBS of TLR4. 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 TLR4
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0004153Atherosclerosis50AlteredExpression, Biomarker, GeneticVariation
umls:C0243026Sepsis42Biomarker, GeneticVariation
umls:C0010346Crohn Disease39Biomarker, GeneticVariation
umls:C0520459Enterocolitis, Necrotizing16Biomarker, GeneticVariation
umls:C0021368Inflammation16AlteredExpression, Biomarker, GeneticVariation
umls:C1956346Coronary Artery Disease12AlteredExpression, Biomarker, GeneticVariation
umls:C0027627Neoplasm Metastasis10Biomarker, GeneticVariation
umls:C0025202Melanoma8AlteredExpression, Biomarker, GeneticVariation
umls:C0948089Acute Coronary Syndrome8Biomarker, GeneticVariation
umls:C0242383Macular Degeneration7Biomarker, GeneticVariation
umls:C0007097Carcinoma7AlteredExpression, Biomarker, GeneticVariation
umls:C1864267Endotoxin Hyporesponsiveness7Biomarker, GeneticVariation
umls:C0009404Colorectal Neoplasms5AlteredExpression, Biomarker, GeneticVariation
umls:C0340288Angina, Stable5Biomarker
umls:C0033578Prostatic Neoplasms4AlteredExpression, Biomarker, GeneticVariation
umls:C0015695Fatty Liver4Biomarker
umls:C0017661Glomerulonephritis, IGA4Biomarker
umls:C0011882Diabetic Neuropathies2Biomarker, GeneticVariation
umls:C0270611Brain Injuries2Biomarker
umls:C0024121Lung Neoplasms2AlteredExpression, Biomarker
umls:C0279628Adenocarcinoma Of Esophagus2Biomarker
umls:C0011616Dermatitis, Contact1Biomarker
umls:C1384666Hearing Loss1Biomarker
umls:C0273115Lung Injury1Biomarker
umls:C0027626Neoplasm Invasiveness1Biomarker
umls:C0919267Ovarian Neoplasms1Biomarker
umls:C0031117Peripheral Nervous System Diseases1Biomarker
umls:C0035228Respiratory Hypersensitivity1Biomarker

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

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Pharmacological information for TLR4
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
Approved|vet_approvedDB01183NaloxoneSmall molecule
ExperimentalDB027673-Hydroxy-Myristic AcidSmall molecule
InvestigationalDB04933EritoranSmall molecule
InvestigationalDB05475SCV-07Small molecule
ExperimentalDB08231MYRISTIC ACIDSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of TLR4 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
NAGALDEHYDO-N-ACETYL-D-GLUCOSAMINE3fxiBD550 N575 V602
NAGALDEHYDO-N-ACETYL-D-GLUCOSAMINE3fxiAD550 S552 N575 T577
FULBETA-L-FUCOSE2z62AE31 Y38 P53
FULBETA-L-FUCOSE2z62AK150
LP5(R)-((2R,3S,4R,5R,6R)-3-HYDROXY-2-(HYDROXYMETHYL)-5-((R)-3-HYDROXYTETRADECANAMIDO)-6-(PHOSPHONOOXY)TETRAHYDRO-2H-PYRAN-4-YL) 3-HYDROXYTETRADECANOATE4g8aAS415 Q436 E439 F440
LP5(R)-((2R,3S,4R,5R,6R)-3-HYDROXY-2-(HYDROXYMETHYL)-5-((R)-3-HYDROXYTETRADECANAMIDO)-6-(PHOSPHONOOXY)TETRAHYDRO-2H-PYRAN-4-YL) 3-HYDROXYTETRADECANOATE4g8aBS415 Q436 E439 F440
NAGALDEHYDO-N-ACETYL-D-GLUCOSAMINE3fxiAS504 N526 D550
NAGALDEHYDO-N-ACETYL-D-GLUCOSAMINE3fxiBS504 N526 D550


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Conservation information for LBS of TLR4
Multiple alignments for O00206 in multiple species
LBSAA sequence# speciesSpecies
D550SLQVLDYSLNH1Homo sapiens
D550SLSTLDCSFNR1Mus musculus
D550SLRTLDCSFNR1Rattus norvegicus
D550SLRILDCSFNR1Bos taurus
E178NLTNLEHLDLS1Homo sapiens
E178NLTNLVHVDLS1Mus musculus
E178NLTNLEHVDLS1Rattus norvegicus
E178NLPNLEHLDLS1Bos taurus
E31WEPCVEVVPNI1Homo sapiens
E31LNPCIEVVPNI1Mus musculus
E31LNPCIEVLPNI1Rattus norvegicus
E31WDPCVQVVPNI1Bos taurus
E439LKQMSEFSVFL1Homo sapiens
E439LKRVTEFSAFL1Mus musculus
E439LKKVTEFSVFL1Rattus norvegicus
E439LKQINAFSAFL1Bos taurus
F440KQMSEFSVFLS1Homo sapiens
F440KRVTEFSAFLS1Mus musculus
F440KKVTEFSVFLS1Rattus norvegicus
F440KQINAFSAFLS1Bos taurus
F573PSSLAFLNLTQ1Homo sapiens
F573PKSLAFFNLTN1Mus musculus
F573PKSLAVFNLTN1Rattus norvegicus
F573PRSLTWLNLTQ1Bos taurus
H148NFPIGHLKTLK1Homo sapiens
H148SFPIGQLITLK1Mus musculus
H148GFHIGQLISLK1Rattus norvegicus
H148DFPIGHLKNLK1Bos taurus
H179LTNLEHLDLSS1Homo sapiens
H179LTNLVHVDLSY1Mus musculus
H179LTNLEHVDLSY1Rattus norvegicus
H179LPNLEHLDLSN1Bos taurus
K150PIGHLKTLKEL1Homo sapiens
K150PIGQLITLKKL1Mus musculus
K150HIGQLISLKKL1Rattus norvegicus
K150PIGHLKNLKEL1Bos taurus
N205QMPLLNLSLDL2Homo sapiens, Bos taurus
N205ENPQVNLSLDM1Mus musculus
N205ENPQVNLSLDL1Rattus norvegicus
N526RLQLLNMSHNN2Mus musculus, Rattus norvegicus
N526SLQVLNMSHNN1Homo sapiens
N526SLQVLNMSHNK1Bos taurus
N575SLAFLNLTQND1Homo sapiens
N575SLAFFNLTNNS1Mus musculus
N575SLAVFNLTNNS1Rattus norvegicus
N575SLTWLNLTQNA1Bos taurus
P13AGTLIPAMAFL1Homo sapiens
P13ARTLIMAL-FF1Mus musculus
P13AGTLIMAL-FL1Rattus norvegicus
P13AAALIPATAIL1Bos taurus
P53IPDNLPFSTKN1Homo sapiens
P53VPDDIPSSTKN1Mus musculus
P53IPHDIPYSTKN1Rattus norvegicus
P53IPDNIPISTKM1Bos taurus
Q436HSNLKQMSEFS1Homo sapiens
Q436HSTLKRVTEFS1Mus musculus
Q436HSTLKKVTEFS1Rattus norvegicus
Q436HSTLKQINAFS1Bos taurus
Q505FLDLSKCQLEQ2Mus musculus, Rattus norvegicus
Q505FLDLSQCQLEQ1Homo sapiens
Q505VLDLSKCQLEQ1Bos taurus
S207PLLNLSLDLSL2Homo sapiens, Bos taurus
S207PQVNLSLDMSL1Mus musculus
S207PQVNLSLDLSL1Rattus norvegicus
S415GVITMSSNFLG1Homo sapiens
S415GAIIMSANFMG1Mus musculus
S415GVILMSANFMG1Rattus norvegicus
S415DVITLGSNFMG1Bos taurus
S504TFLDLSKCQLE2Mus musculus, Rattus norvegicus
S504TFLDLSQCQLE1Homo sapiens
S504TVLDLSKCQLE1Bos taurus
S552QVLDYSLNHIM1Homo sapiens
S552STLDCSFNRIE1Mus musculus
S552RTLDCSFNRIE1Rattus norvegicus
S552RILDCSFNRIM1Bos taurus
T577AFLNLTQNDFA1Homo sapiens
T577AFFNLTNNSVA1Mus musculus
T577AVFNLTNNSVA1Rattus norvegicus
T577TWLNLTQNAFA1Bos taurus
V602QRQLLVEVERM1Homo sapiens
V602QKQFLVNVEQM1Mus musculus
V602QKMFLVNVEQM1Rattus norvegicus
V602QRQLLVGAEQM1Bos taurus
Y38VPNITYQCMEL1Homo sapiens
Y38VPNITYQCMDQ1Mus musculus
Y38LPNITYQCMDQ1Rattus norvegicus
Y38VPNISYQCMEL1Bos taurus


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