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 BRD4

Gene summary

Basic gene Info.	Gene symbol	BRD4
	Gene name	bromodomain containing 4
	Synonyms	CAP\|HUNK1\|HUNKI\|MCAP
	Cytomap	UCSC genome browser: 19p13.1
	Type of gene	protein-coding
	RefGenes	NM_014299.2, NM_058243.2,
	Description	bromodomain-containing 4bromodomain-containing protein 4chromosome-associated protein
	Modification date	20141222
dbXrefs	MIM : 608749
	HGNC : HGNC
	Ensembl : ENSG00000141867
	HPRD : 10574
	Vega : OTTHUMG00000183252
Protein	UniProt: O60885 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_BRD4
	BioGPS: 23476
Pathway	NCI Pathway Interaction Database: BRD4
	KEGG: BRD4
	REACTOME: BRD4
	Pathway Commons: BRD4
Context	iHOP: BRD4
	ligand binding site mutation search in PubMed: BRD4
	UCL Cancer Institute: BRD4
Assigned class in mutLBSgeneDB	B: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez

GO ID	GO Term	PubMed ID
GO:0006338	chromatin remodeling	23728299
GO:0032968	positive regulation of transcription elongation from RNA polymerase II promoter	19103749
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling	19103749
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	23086925
GO:0050727	regulation of inflammatory response	19103749
GO:1901407	regulation of phosphorylation of RNA polymerase II C-terminal domain	23086925

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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

LBS	AAchange of nsSNV	Cancer type	# samples
V90,D88	A89V	COAD	1
M425	F426L	GBM	1
I393	I394M	HNSC	1
P375	P375L	SKCM	1
P95	P95T	SKCM	1
D96	D96N	UCEC	1

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.

LBS	AAchange of nsSNV	Relative stability change
P375	P375L	0.038494297
I393	I394M	-1.7103471
P95	P95T	-1.4355776
D96	D96N	-1.1169378
M425	F426L	-0.58041424
D88	A89V	-0.50923202
V90	A89V	-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 ID

Disease name

# PubMed

Association type

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype 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 status

DrugBank ID

Name

Type

Drug structure

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of BRD4 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
25V		N-[3-(2-METHYL-1-OXIDOQUINOLIN-4-YL)PHENYL]ACETAMIDE	4meo	A	D88
2R4	NU7441	8-(DIBENZO[B,D]THIOPHEN-4-YL)-2-(MORPHOLIN-4-YL)-4H- CHROMEN-4-ONE	4o72	A	D88
WSH		BENZYL [(4R)-1-METHYL-6-PHENYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]CARBAMATE	2yem	A	P375
WSH		BENZYL [(4R)-1-METHYL-6-PHENYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]CARBAMATE	2yem	B	P375
4LD		1-(3-CYCLOPROPYL-5-METHYL-1H-PYRAZOL-4-YL)-7-(3,5- DIMETHYL-1,2-OXAZOL-4-YL)-8-METHOXY-5H-PYRIDO[4,3- B]INDOLE	4z93	A	P375
III		Peptide ligand (ARG,THR,TYR,GLU,THR,PHE,LYS,SER,ILE,MET,LYS,LYS,SER)	2lsp	B	P375 I393
III		Peptide ligand (SER,PRO,ALA,GLN,GLY,LYS,ARG,GLY,LYS,LYS,SER,ALA)	2mjv	B	P375 I393 M425
III		Peptide ligand (SER,GLY,ARG,GLY,LYS,GLY,GLY,LYS,GLY,LEU,GLY,TYR)	3uvw	A	P95 D96
1QK	DINACICLIB	3-[({3-ETHYL-5-[(2S)-2-(2-HYDROXYETHYL)PIPERIDIN-1- YL]PYRAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)METHYL]-1- HYDROXYPYRIDINIUM	4o70	A	V90

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Conservation information for LBS of BRD4

Multiple alignments for O60885 in multiple species

LBS

AA sequence

# species

Species