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 TBX5

Gene summary

Basic gene Info.	Gene symbol	TBX5
	Gene name	T-box 5
	Synonyms	HOS
	Cytomap	UCSC genome browser: 12q24.1
	Type of gene	protein-coding
	RefGenes	NM_000192.3, NM_080717.2,NM_181486.2,NM_080718.1,
	Description	T-box protein 5T-box transcription factor TBX5
	Modification date	20141219
dbXrefs	MIM : 601620
	HGNC : HGNC
	Ensembl : ENSG00000089225
	HPRD : 03372
	Vega : OTTHUMG00000166191
Protein	UniProt: Q99593 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_TBX5
	BioGPS: 6910
Pathway	NCI Pathway Interaction Database: TBX5
	KEGG: TBX5
	REACTOME: TBX5
	Pathway Commons: TBX5
Context	iHOP: TBX5
	ligand binding site mutation search in PubMed: TBX5
	UCL Cancer Institute: TBX5
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:0007267	cell-cell signaling	11161571
GO:0007507	heart development	15138308
GO:0008285	negative regulation of cell proliferation	11161571
GO:0030262	apoptotic nuclear changes	12237100
GO:0030336	negative regulation of cell migration	15138308
GO:0045893	positive regulation of transcription, DNA-templated	11431700
GO:0051891	positive regulation of cardioblast differentiation	11431700
GO:0060039	pericardium development	15138308
GO:0060044	negative regulation of cardiac muscle cell proliferation	11161571

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Ligand binding site mutations for TBX5

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
S175	L173P	COAD	1
F236	R237L	LUAD	1
P231	P231H	LUAD	1
S175	L173Q	OV	1
H59	L58F	SKCM	1
N162	H164Y	SKCM	1
S175	S175F	SKCM	1
R82	R82Q	STAD	1
R82	M83L	STAD	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 TBX5

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
S175	L173Q	-1.482894
H59	L58F	-1.4195499
S175	L173P	-1.3188417
P231	P231H	-1.1336769
R82	R82Q	-0.86335786
N162	H164Y	-0.59675123
S175	S175F	-0.44453319
R82	M83L	-0.43396865
F236	R237L	-0.11846298

(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 TBX5 from PDB

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Differential gene expression and gene-gene network for TBX5

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 TBX5 and the right PPI network was created from samples without mutations in the LBS of TBX5. 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 TBX5

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0265264	Holt-Oram syndrome	39	Biomarker, GeneticVariation
umls:C0018798	Heart Defects, Congenital	9	Biomarker, GeneticVariation

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for TBX5

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 TBX5 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
MG		MAGNESIUM(2+)	2x6v	A	H59
MG		MAGNESIUM(2+)	2x6u	A	N162
NUC		Nucleic Acids	2x6v	A	N162 S175 P231
NUC		Nucleic Acids	4s0h	A	N162 S175 P231
NUC		Nucleic Acids	4s0h	E	N162 S175 P231
MG		MAGNESIUM(2+)	2x6u	A	R82
NUC		Nucleic Acids	2x6v	A	R82 F236
NUC		Nucleic Acids	4s0h	A	R82 F236
NUC		Nucleic Acids	4s0h	E	R82 F236

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Conservation information for LBS of TBX5

Multiple alignments for Q99593 in multiple species

LBS	AA sequence	# species	Species
E60	KVFLHERELWL	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
F232	IENNPFAKGFR	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
F236	PFAKGFRGSDD	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
G125	KWSVTGKAEPA	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
G235	NPFAKGFRGSD	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
H112	VPADDHRYKFA	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
H59	IKVFLHERELW	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
I227	ITQLKIENNPF	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
I75	VGTEMIITKAG	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
K126	WSVTGKAEPAM	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
K159	SFQKLKLTNNH	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
K226	KITQLKIENNP	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
K234	NNPFAKGFRGS	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
K78	EMIITKAGRRM	3	Homo sapiens, Gallus gallus, Mus musculus
K78	EMIITKAGRQM	1	Rattus norvegicus
K88	MFPSYKVKVTG	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
M176	IILNSMHKYQP	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
N162	KLKLTNNHLDP	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
N230	LKIENNPFAKG	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
P231	KIENNPFAKGF	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
R81	ITKAGRRMFPS	3	Homo sapiens, Gallus gallus, Mus musculus
R81	ITKAGRQMFPS	1	Rattus norvegicus
R82	TKAGRRMFPSY	3	Homo sapiens, Gallus gallus, Mus musculus
R82	TKAGRQMFPSY	1	Rattus norvegicus
S175	HIILNSMHKYQ	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
S86	RRMFPSYKVKV	3	Homo sapiens, Gallus gallus, Mus musculus
S86	RQMFPSYKVKV	1	Rattus norvegicus
T215	AFIAVTSYQNH	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
T223	QNHKITQLKIE	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus
Y217	IAVTSYQNHKI	4	Homo sapiens, Gallus gallus, Rattus norvegicus, Mus musculus