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 BRD4
Gene summary
Basic gene Info.Gene symbolBRD4
Gene namebromodomain containing 4
SynonymsCAP|HUNK1|HUNKI|MCAP
CytomapUCSC genome browser: 19p13.1
Type of geneprotein-coding
RefGenesNM_014299.2,
NM_058243.2,
Descriptionbromodomain-containing 4bromodomain-containing protein 4chromosome-associated protein
Modification date20141222
dbXrefs MIM : 608749
HGNC : HGNC
Ensembl : ENSG00000141867
HPRD : 10574
Vega : OTTHUMG00000183252
ProteinUniProt: O60885
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_BRD4
BioGPS: 23476
PathwayNCI Pathway Interaction Database: BRD4
KEGG: BRD4
REACTOME: BRD4
Pathway Commons: BRD4
ContextiHOP: BRD4
ligand binding site mutation search in PubMed: BRD4
UCL Cancer Institute: BRD4
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:0006338chromatin remodeling23728299
GO:0032968positive regulation of transcription elongation from RNA polymerase II promoter19103749
GO:0043123positive regulation of I-kappaB kinase/NF-kappaB signaling19103749
GO:0045944positive regulation of transcription from RNA polymerase II promoter23086925
GO:0050727regulation of inflammatory response19103749
GO:1901407regulation of phosphorylation of RNA polymerase II C-terminal domain23086925


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Ligand binding site mutations for BRD4
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
V90,D88A89VCOAD1
M425F426LGBM1
I393I394MHNSC1
P375P375LSKCM1
P95P95TSKCM1
D96D96NUCEC1
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 BRD4
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
P375P375L0.038494297
I393I394M-1.7103471
P95P95T-1.4355776
D96D96N-1.1169378
M425F426L-0.58041424
D88A89V-0.50923202
V90A89V-0.50923202
(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 BRD4 from PDB

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Differential gene expression and gene-gene network for BRD4
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 BRD4 and the right PPI network was created from samples without mutations in the LBS of BRD4. 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 BRD4
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 BRD4
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

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of BRD4 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
25VN-[3-(2-METHYL-1-OXIDOQUINOLIN-4-YL)PHENYL]ACETAMIDE4meoAD88
2R4NU74418-(DIBENZO[B,D]THIOPHEN-4-YL)-2-(MORPHOLIN-4-YL)-4H- CHROMEN-4-ONE4o72AD88
WSHBENZYL [(4R)-1-METHYL-6-PHENYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]CARBAMATE2yemAP375
WSHBENZYL [(4R)-1-METHYL-6-PHENYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]CARBAMATE2yemBP375
4LD1-(3-CYCLOPROPYL-5-METHYL-1H-PYRAZOL-4-YL)-7-(3,5- DIMETHYL-1,2-OXAZOL-4-YL)-8-METHOXY-5H-PYRIDO[4,3- B]INDOLE4z93AP375
IIIPeptide ligand (ARG,THR,TYR,GLU,THR,PHE,LYS,SER,ILE,MET,LYS,LYS,SER)2lspBP375 I393
IIIPeptide ligand (SER,PRO,ALA,GLN,GLY,LYS,ARG,GLY,LYS,LYS,SER,ALA)2mjvBP375 I393 M425
IIIPeptide ligand (SER,GLY,ARG,GLY,LYS,GLY,GLY,LYS,GLY,LEU,GLY,TYR)3uvwAP95 D96
1QKDINACICLIB3-[({3-ETHYL-5-[(2S)-2-(2-HYDROXYETHYL)PIPERIDIN-1- YL]PYRAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)METHYL]-1- HYDROXYPYRIDINIUM4o70AV90


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Conservation information for LBS of BRD4
Multiple alignments for O60885 in multiple species
LBSAA sequence# speciesSpecies


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