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 RPS6KA3

Gene summary

Basic gene Info.	Gene symbol	RPS6KA3
	Gene name	ribosomal protein S6 kinase, 90kDa, polypeptide 3
	Synonyms	CLS\|HU-3\|ISPK-1\|MAPKAPK1B\|MRX19\|RSK\|RSK2\|S6K-alpha3\|p90-RSK2\|pp90RSK2
	Cytomap	UCSC genome browser: Xp22.2-p22.1
	Type of gene	protein-coding
	RefGenes	NM_004586.2,
	Description	MAP kinase-activated protein kinase 1bMAPK-activated protein kinase 1bMAPKAP kinase 1bMAPKAPK-1bRSK-2S6K-alpha-3insulin-stimulated protein kinase 1p90-RSK 3ribosomal S6 kinase 2ribosomal protein S6 kinase alpha-3
	Modification date	20141219
dbXrefs	MIM : 300075
	HGNC : HGNC
	Ensembl : ENSG00000177189
	HPRD : 02092
	Vega : OTTHUMG00000021231
Protein	UniProt: P51812 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_RPS6KA3
	BioGPS: 6197
Pathway	NCI Pathway Interaction Database: RPS6KA3
	KEGG: RPS6KA3
	REACTOME: RPS6KA3
	Pathway Commons: RPS6KA3
Context	iHOP: RPS6KA3
	ligand binding site mutation search in PubMed: RPS6KA3
	UCL Cancer Institute: RPS6KA3
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:0043154	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	18402937

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Ligand binding site mutations for RPS6KA3

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
R151	R151S	LUAD	1
L74	K72Q	UCEC	1
L467	R469C	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 RPS6KA3

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
L467	R469C	-1.3878874
R151	R151S	-1.0651927
L74	K72Q	-0.52291594

(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 RPS6KA3 from PDB

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Differential gene expression and gene-gene network for RPS6KA3

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 RPS6KA3 and the right PPI network was created from samples without mutations in the LBS of RPS6KA3. 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 RPS6KA3

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0265252	Coffin-Lowry Syndrome	40	AlteredExpression, Biomarker, GeneticVariation
umls:C0027627	Neoplasm Metastasis	4	Biomarker
umls:C2239176	Carcinoma, Hepatocellular	1	Biomarker
umls:C0005941	Bone Diseases, Developmental	1	Biomarker
umls:C0027626	Neoplasm Invasiveness	1	Biomarker
umls:C0033922	Psychomotor Disorders	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for RPS6KA3

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\|vet_approved	DB00945	Acetylsalicylic acid	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of RPS6KA3 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
0JH		TERT-BUTYL (2S)-3-[4-AMINO-7-(3-HYDROXYPROPYL)-5-(4-METHYLPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-6-YL]-2-CYANOPROPANOATE	4d9u	A	L467
584		(7R)-2-[(3,5-DIFLUORO-4-HYDROXYPHENYL)AMINO]-5,7- DIMETHYL-8-(3-METHYLBUTYL)-7,8-DIHYDROPTERIDIN-6(5H)- ONE	5d9k	A	L74
584		(7R)-2-[(3,5-DIFLUORO-4-HYDROXYPHENYL)AMINO]-5,7- DIMETHYL-8-(3-METHYLBUTYL)-7,8-DIHYDROPTERIDIN-6(5H)- ONE	5d9k	B	L74
583		4,4'-(1H-PYRAZOLE-3,4-DIYL)DIPHENOL	5d9l	A	L74
2NR		7-(2-FLUORO-6-METHOXYPHENYL)-N-(3,4,5- TRIMETHOXYPHENYL)-1,3-BENZOXAZOL-2-AMINE	4nw5	A	L74 R151
2NS		7-(1H-BENZIMIDAZOL-7-YL)-N-(3,4,5-TRIMETHOXYPHENYL)-1, 3-BENZOXAZOL-2-AMINE	4nw6	A	L74 R151

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Conservation information for LBS of RPS6KA3

Multiple alignments for P51812 in multiple species

LBS

AA sequence

# species

Species