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 BRD2

Gene summary

Basic gene Info.	Gene symbol	BRD2
	Gene name	bromodomain containing 2
	Synonyms	D6S113E\|FSH\|FSRG1\|NAT\|RING3\|RNF3
	Cytomap	UCSC genome browser: 6p21.3
	Type of gene	protein-coding
	RefGenes	NM_001113182.2, NM_001199455.1,NM_001199456.1,NM_005104.3,NR_037625.1, NM_001291986.1,
	Description	O27.1.1bromodomain-containing 2bromodomain-containing protein 2female sterile homeotic-related gene 1really interesting new gene 3 protein
	Modification date	20141207
dbXrefs	MIM : 601540
	HGNC : HGNC
	Ensembl : ENSG00000204256
	HPRD : 03326
	Vega : OTTHUMG00000031241
Protein	UniProt: P25440 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_BRD2
	BioGPS: 6046
Pathway	NCI Pathway Interaction Database: BRD2
	KEGG: BRD2
	REACTOME: BRD2
	Pathway Commons: BRD2
Context	iHOP: BRD2
	ligand binding site mutation search in PubMed: BRD2
	UCL Cancer Institute: BRD2
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:0006357	regulation of transcription from RNA polymerase II promoter	18406326

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Ligand binding site mutations for BRD2

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
D160	D160Y	COAD	2
C425	N424K	BLCA	1
P430	P430S	COAD	1
W370	A369T	COAD	1
Q101,F99	R100L	LUAD	1
D160	D160N	OV	1
Y153	Y153H	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 BRD2

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
Y153	Y153H	-1.3527918
P430	P430S	-1.1187285
D160	D160N	-1.0996831
D160	D160Y	-0.70822268
F99	R100L	-0.33408597
Q101	R100L	-0.33408597
W370	A369T	-0.30401569
C425	N424K	-0.14861214

(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 BRD2 from PDB

PDB ID	PDB title	PDB structure
1X0J	Crystal structure analysis of the N-terminal bromodomain of human Brd2

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Differential gene expression and gene-gene network for BRD2

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 BRD2 and the right PPI network was created from samples without mutations in the LBS of BRD2. 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 BRD2

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 BRD2

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.

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 BRD2 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
WSH		BENZYL [(4R)-1-METHYL-6-PHENYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]CARBAMATE	2ydw	C	D160
EAM		2-[(4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1-METHYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]-N-ETHYLACETAMIDE	2yek	A	F99
EAM		2-[(4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1-METHYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]-N-ETHYLACETAMIDE	2yek	B	F99
3PF		3-METHYL-3,4-DIHYDROQUINAZOLIN-2(1H)-ONE	4a9e	A	F99
3PF		3-METHYL-3,4-DIHYDROQUINAZOLIN-2(1H)-ONE	4a9e	B	F99
MB3		N-METHYLPYRROLIDIN-2-ONE	4a9f	A	F99
MB3		N-METHYLPYRROLIDIN-2-ONE	4a9f	B	F99
MB3		N-METHYLPYRROLIDIN-2-ONE	4a9f	C	F99
TVP		(2S)-1-ACETYL-2-METHYL-1,2,3,4-TETRAHYDROQUINOLINE	4a9h	A	F99
TVP		(2S)-1-ACETYL-2-METHYL-1,2,3,4-TETRAHYDROQUINOLINE	4a9h	B	F99
TVP		(2S)-1-ACETYL-2-METHYL-1,2,3,4-TETRAHYDROQUINOLINE	4a9h	C	F99
P9I		1-[1-(PYRIDIN-2-YL)INDOLIZIN-3-YL]ETHAN-1-ONE	4a9i	B	F99
P9M		N-CYCLOPENTYL-5-(3,5-DIMETHYLISOXAZOL-4-YL)-2-METHYLBENZENESULFONAMIDE	4a9m	A	F99
P9M		N-CYCLOPENTYL-5-(3,5-DIMETHYLISOXAZOL-4-YL)-2-METHYLBENZENESULFONAMIDE	4a9m	B	F99
P9M		N-CYCLOPENTYL-5-(3,5-DIMETHYLISOXAZOL-4-YL)-2-METHYLBENZENESULFONAMIDE	4a9m	C	F99
A9N		N-CYCLOPROP-2-EN-1-YL-5-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)-2-METHYL-BENZENESULFONAMIDE	4a9n	A	F99
A9N		N-CYCLOPROP-2-EN-1-YL-5-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)-2-METHYL-BENZENESULFONAMIDE	4a9n	B	F99
A9O		5 ETHYL-3-METHYL-4-PHENYL-1,2-OXAZOLE	4a9o	A	F99
A9O		5 ETHYL-3-METHYL-4-PHENYL-1,2-OXAZOLE	4a9o	B	F99
A9O		5 ETHYL-3-METHYL-4-PHENYL-1,2-OXAZOLE	4a9o	C	F99
S5B		4-[(2-TERT-BUTYLPHENYL)AMINO]-7-(3,5- DIMETHYL -1,2-OXAZOL-4-YL)QUINOLINE-3-CARBOXYLIC ACID	4akn	A	F99
S5B		4-[(2-TERT-BUTYLPHENYL)AMINO]-7-(3,5- DIMETHYL -1,2-OXAZOL-4-YL)QUINOLINE-3-CARBOXYLIC ACID	4akn	B	F99
A9P		3,5-DIMETHYL-4-PHENYL-1,2-OXAZOLE	4alh	A	F99
A9P		3,5-DIMETHYL-4-PHENYL-1,2-OXAZOLE	4alh	B	F99
A9P		3,5-DIMETHYL-4-PHENYL-1,2-OXAZOLE	4alh	C	F99
73B		4-[(2S,4R)-1-ACETYL-4-[(4-CHLOROPHENYL)AMINO] -2-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL] BENZOIC ACID	4uyf	A	F99
73B		4-[(2S,4R)-1-ACETYL-4-[(4-CHLOROPHENYL)AMINO] -2-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL] BENZOIC ACID	4uyf	B	F99
73B		4-[(2S,4R)-1-ACETYL-4-[(4-CHLOROPHENYL)AMINO] -2-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL] BENZOIC ACID	4uyf	C	F99
9S3		1-[(2S,4R)-2-METHYL-4-(PHENYLAMINO)-6-[4- (PIPERIDIN-1-YLMETHYL)PHENYL]-3,4- DIHYDROQUINOLIN-1(2H)-YL]ETHANONE	4uyh	A	F99
9S3		1-[(2S,4R)-2-METHYL-4-(PHENYLAMINO)-6-[4- (PIPERIDIN-1-YLMETHYL)PHENYL]-3,4- DIHYDROQUINOLIN-1(2H)-YL]ETHANONE	4uyh	B	F99
III		Peptide ligand (LYS,GLY,LEU,GLY,LYS,GLY,GLY,ALA)	2dvq	A	F99 D160
P9I		1-[1-(PYRIDIN-2-YL)INDOLIZIN-3-YL]ETHAN-1-ONE	4a9i	C	F99 Q101
III		Peptide ligand (SER,GLY,ARG,GLY,LYS,GLY,GLY,LYS,GLY,LEU,GLY,LYS,GLY,GLY,ALA)	2dvq	B	F99 Y153 D160
III		Peptide ligand (SER,GLY,ARG,GLY,LYS,GLY,GLY,LYS,GLY,LEU,GLY,LYS,GLY,GLY,ALA)	2e3k	C	P430
III		Peptide ligand (ARG,GLY,LYS,GLY,GLY,LYS,GLY,LEU,GLY,LYS,GLY,GLY,ALA)	2e3k	D	P430
JQ1		(6S)-6-(2-TERT-BUTOXY-2-OXOETHYL)-4-(4-CHLOROPHENYL)-2,3,9-TRIMETHYL-6,7-DIHYDROTHIENO[3,2-F][1,2,4]TRIAZOLO[4,3-A][1,4]DIAZEPIN-10-IUM	3oni	A	W370
1K0		2-[4-(2-HYDROXYETHOXY)-3,5-DIMETHYLPHENYL]-5,7- DIMETHOXYQUINAZOLIN-4(3H)-ONE	4mr5	A	W370
73B		4-[(2S,4R)-1-ACETYL-4-[(4-CHLOROPHENYL)AMINO] -2-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL] BENZOIC ACID	4uyg	F	W370
31O		METHYL (2R)-2-[(4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1- METHYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4- YL]PROPANOATE	4qev	A	W370
31P		METHYL (2R)-2-[(4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1- METHYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4- YL]BUTANOATE	4qew	A	W370
73B		4-[(2S,4R)-1-ACETYL-4-[(4-CHLOROPHENYL)AMINO] -2-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL] BENZOIC ACID	4uyg	A	W370 C425
73B		4-[(2S,4R)-1-ACETYL-4-[(4-CHLOROPHENYL)AMINO] -2-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL] BENZOIC ACID	4uyg	B	W370 C425
73B		4-[(2S,4R)-1-ACETYL-4-[(4-CHLOROPHENYL)AMINO] -2-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL] BENZOIC ACID	4uyg	C	W370 C425
73B		4-[(2S,4R)-1-ACETYL-4-[(4-CHLOROPHENYL)AMINO] -2-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL] BENZOIC ACID	4uyg	D	W370 C425
73B		4-[(2S,4R)-1-ACETYL-4-[(4-CHLOROPHENYL)AMINO] -2-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL] BENZOIC ACID	4uyg	E	W370 C425
2LO		2-[2-(3-CHLORO-4-METHOXYPHENYL)ETHYL]-5-(3,5-DIMETHYL- 1,2-OXAZOL-4-YL)-1-[(2S)-2-(MORPHOLIN-4-YL)PROPYL]-1H- BENZIMIDAZOLE	5bt5	A	W370 C425
1K0		2-[4-(2-HYDROXYETHOXY)-3,5-DIMETHYLPHENYL]-5,7- DIMETHOXYQUINAZOLIN-4(3H)-ONE	4mr6	A	W370 P430
III		Peptide ligand (SER,GLY,ARG,GLY,LYS,GLY,GLY,LYS,GLY,LEU,GLY,LYS,GLY,GLY,ALA)	2dvq	A	Y153

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Conservation information for LBS of BRD2

Multiple alignments for P25440 in multiple species

LBS	AA sequence	# species	Species
C152	TMFTNCYIYNK	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
C425	LMFSNCYKYNP	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
D112	KLGLPDYHKII	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
D160	YNKPTDDIVLM	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
D161	NKPTDDIVLMA	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
D385	ALGLHDYHDII	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
D432	KYNPPDHDVVA	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
D434	NPPDHDVVAMA	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
F372	AYAWPFYKPVD	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
F99	QFAWPFRQPVD	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
H384	SALGLHDYHDI	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
H433	YNPPDHDVVAM	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
I116	PDYHKIIKQPM	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
I117	DYHKIIKQPMD	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
I154	FTNCYIYNKPT	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
I162	KPTDDIVLMAQ	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
K107	PVDAVKLGLPD	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
K115	LPDYHKIIKQP	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
K118	YHKIIKQPMDM	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
K157	CYIYNKPTDDI	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
K374	AWPFYKPVDAS	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
L108	VDAVKLGLPDY	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
L110	AVKLGLPDYHK	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
L381	VDASALGLHDY	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
L383	ASALGLHDYHD	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
M165	DDIVLMAQTLE	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
M438	HDVVAMARKLQ	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
N151	NTMFTNCYIYN	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
N156	NCYIYNKPTDD	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
N429	NCYKYNPPDHD	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
P158	YIYNKPTDDIV	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
P371	AAYAWPFYKPV	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
P430	CYKYNPPDHDV	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
P98	HQFAWPFRQPV	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
Q101	AWPFRQPVDAV	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
Q119	HKIIKQPMDMG	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
Q167	IVLMAQTLEKI	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
T159	IYNKPTDDIVL	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
V103	PFRQPVDAVKL	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
V376	PFYKPVDASAL	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
V435	PPDHDVVAMAR	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
W370	HAAYAWPFYKP	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
W97	KHQFAWPFRQP	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
Y113	LGLPDYHKIIK	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
Y153	MFTNCYIYNKP	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
Y155	TNCYIYNKPTD	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
Y386	LGLHDYHDIIK	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris
Y428	SNCYKYNPPDH	6	Homo sapiens, Rattus norvegicus, Rattus norvegicus, Mus musculus, Bos taurus, Canis lupus familiaris