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 ITGA4

Gene summary

Basic gene Info.	Gene symbol	ITGA4
	Gene name	integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
	Synonyms	CD49D\|IA4
	Cytomap	UCSC genome browser: 2q31.3
	Type of gene	protein-coding
	RefGenes	NM_000885.4,
	Description	269C wild typeCD49 antigen-like family member DVLA-4 subunit alphaantigen CD49D, alpha-4 subunit of VLA-4 receptorintegrin alpha 4integrin alpha-4integrin alpha-4 subunitintegrin alpha-IVvery late activation protein 4 receptor, alpha 4 subunit
	Modification date	20141207
dbXrefs	MIM : 192975
	HGNC : HGNC
	HPRD : 01894
Protein	UniProt: P13612 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_ITGA4
	BioGPS: 3676
Pathway	NCI Pathway Interaction Database: ITGA4
	KEGG: ITGA4
	REACTOME: ITGA4
	Pathway Commons: ITGA4
Context	iHOP: ITGA4
	ligand binding site mutation search in PubMed: ITGA4
	UCL Cancer Institute: ITGA4
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:0007159	leukocyte cell-cell adhesion	1715889
GO:0090074	negative regulation of protein homodimerization activity	12869515

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Ligand binding site mutations for ITGA4

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
D439	D439N	BLCA	1
D314	A312S	COAD	1
N404	I402S	COAD	1
D318,N316	A317S	LUAD	1
N404	N404S	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 ITGA4

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
N404	I402S	-1.6628071
N316	A317S	-1.1782468
D318	A317S	-1.1782468
D439	D439N	-0.54539028
D314	A312S	-0.54503161
N404	N404S	-0.29730439

(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 ITGA4 from PDB

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Differential gene expression and gene-gene network for ITGA4

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 ITGA4 and the right PPI network was created from samples without mutations in the LBS of ITGA4. 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 ITGA4

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0023434	Leukemia, Lymphocytic, Chronic, B-Cell	14	AlteredExpression, Biomarker, GeneticVariation
umls:C0004352	Autistic Disorder	4	Biomarker, GeneticVariation
umls:C0017639	Gliosis	1	Biomarker
umls:C0017661	Glomerulonephritis, IGA	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for ITGA4

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
Approved\|investigational	DB00108	Natalizumab	Biotech
Investigational	DB04997	ATL1102	Small molecule
Investigational	DB05092	CDP323	Small molecule
Investigational	DB05122	R1295	Small molecule
Investigational	DB05468	R411	Small molecule
Investigational	DB05802	MLN-02	Small molecule
Approved	DB06822	Tinzaparin	Small molecule
Approved	DB09033	Vedolizumab	Biotech