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 RHEB

Gene summary

Basic gene Info.	Gene symbol	RHEB
	Gene name	Ras homolog enriched in brain
	Synonyms	RHEB2
	Cytomap	UCSC genome browser: 7q36
	Type of gene	protein-coding
	RefGenes	NM_005614.3,
	Description	GTP-binding protein RhebRas homolog enriched in brain 2
	Modification date	20141207
dbXrefs	MIM : 601293
	HGNC : HGNC
	Ensembl : ENSG00000106615
	HPRD : 03188
	Vega : OTTHUMG00000157330
Protein	UniProt: Q15382 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_RHEB
	BioGPS: 6009
Pathway	NCI Pathway Interaction Database: RHEB
	KEGG: RHEB
	REACTOME: RHEB
	Pathway Commons: RHEB
Context	iHOP: RHEB
	ligand binding site mutation search in PubMed: RHEB
	UCL Cancer Institute: RHEB
Assigned class in mutLBSgeneDB	C: This gene just belongs to mutLBSgenes.

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

GO ID

GO Term

PubMed ID

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Ligand binding site mutations for RHEB

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
Y35	Y35N	KIRC	2
Y35	Y35N	UCEC	2
S21	S21L	BLCA	1
F31	G29S	BRCA	1
Y35	Y35H	KIRC	1
S21	T23M	LUAD	1
G63	G63W	LUSC	1
D60	L58R	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.

Clinical information for RHEB from My Cancer Genome.

Ras homolog enriched in brain (RHEB) is a gene that encodes a lipid-anchored, cell membrane protein. The proteinregulates cell growth and cell cycle progression. Missense, nonsense, and silent mutations are observed in cancers such as endometrial cancer, intestinal cancer, and stomach cancer.Modified: July 1, 2015

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Protein structure related information for RHEB

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
Y35	Y35N	-1.5526423
Y35	Y35H	-1.5058563
D60	L58R	-1.4502069
F31	G29S	-1.0186426
S21	T23M	-0.54311604
S21	S21L	-0.39226538
G63	G63W	-0.37466507

(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 RHEB from PDB

PDB ID	PDB title	PDB structure
1XTQ	Structure of small GTPase human Rheb in complex with GDP

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Differential gene expression and gene-gene network for RHEB

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

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0007131	Carcinoma, Non-Small-Cell Lung	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for RHEB

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
Experimental	DB04137	Guanosine-5'-Triphosphate	Small molecule
Experimental	DB04315	Guanosine-5'-Diphosphate	Small molecule

Gene-centered ligand-gene interaction network

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

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
MG		MAGNESIUM(2+)	1xtr	A	D60
GDP		GUANOSINE-5'-DIPHOSPHATE	1xtq	A	S21 F31
GDP		GUANOSINE-5'-DIPHOSPHATE	3sea	A	S21 F31
GDP		GUANOSINE-5'-DIPHOSPHATE	3t5g	A	S21 F31
GNP		PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER	3sea	B	S21 F31 G63
GNP		PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER	1xtr	A	S21 F31 Y35 G63
GTP		GTP	1xts	A	S21 F31 Y35 G63

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Conservation information for LBS of RHEB

Multiple alignments for Q15382 in multiple species

LBS	AA sequence	# species	Species
A150	FLESSAKENQT	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
A150	FIECSAELDYN	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
A150	FVEITARESNR	1	Caenorhabditis elegans
A150	WTEASARHNEN	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
C181	GKSS-CSVM	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
C181	NNNK-CSIM	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
C181	GKP--CSIS	1	Caenorhabditis elegans
C181	GDGKGCVIA	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D122	VGNKKDL----	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
D122	VGTKADLGRST	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D122	VGNKTDL----	1	Caenorhabditis elegans
D122	VGNKSDL----	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D33	EGQFVDSYDPT	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
D33	ESRFVESYYPT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D33	QNIFPERYEST	1	Caenorhabditis elegans
D33	ENHFVESYYPT	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D36	FVDSYDPTIEN	3	Homo sapiens, Mus musculus, Rattus norvegicus
D36	FVESYYPTIEN	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D36	FPERYESTIED	1	Caenorhabditis elegans
D36	FVDSYDPTIKN	1	Bos taurus
D60	HLQLVDTAGQD	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
D60	TLEILDTAGQD	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D60	HLRVTDTAGQQ	1	Caenorhabditis elegans
D60	ATEIIDTAGQD	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F31	FVEGQFVDSYD	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
F31	FVESRFVESYY	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
F31	FTQNIFPERYE	1	Caenorhabditis elegans
F31	YVENHFVESYY	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G18	GYRSVGKSSLT	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
G18	GARNVGKTTLT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G18	GYPHVGKSALV	1	Caenorhabditis elegans
G18	GSRSVGKSSLT	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G63	LVDTAGQDEYS	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
G63	ILDTAGQDEVS	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G63	VTDTAGQQEYT	1	Caenorhabditis elegans
G63	IIDTAGQDEYS	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K120	MLVGNKKDL--	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
K120	ILVGTKADLGR	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K120	VIVGNKTDL--	1	Caenorhabditis elegans
K120	VVVGNKSDL--	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K151	LESSAKENQTA	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
K151	IECSAELDYNV	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K151	VEITARESNRV	1	Caenorhabditis elegans
K151	TEASARHNENV	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K19	YRSVGKSSLTI	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
K19	ARNVGKTTLTV	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K19	YPHVGKSALVL	1	Caenorhabditis elegans
K19	SRSVGKSSLTV	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L123	GNKKDL-----	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
L123	GTKADLGRSTK	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L123	GNKTDL-----	1	Caenorhabditis elegans
L123	GNKSDL-----	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
N119	IMLVGNKKDL-	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
N119	VILVGTKADLG	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N119	IVIVGNKTDL-	1	Caenorhabditis elegans
N119	IVVVGNKSDL-	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
P37	VDSYDPTIENT	3	Homo sapiens, Mus musculus, Rattus norvegicus
P37	VESYYPTIENE	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
P37	PERYESTIEDQ	1	Caenorhabditis elegans
P37	VESYYPTIENT	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
P37	VDSYDPTIKNT	1	Bos taurus
R15	AILGYRSVGKS	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
R15	ALIGARNVGKT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
R15	AVMGYPHVGKS	1	Caenorhabditis elegans
R15	AVLGSRSVGKS	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S149	AFLESSAKENQ	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
S149	AFIECSAELDY	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S149	KFVEITARESN	1	Caenorhabditis elegans
S149	AWTEASARHNE	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S16	ILGYRSVGKSS	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
S16	LIGARNVGKTT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S16	VMGYPHVGKSA	1	Caenorhabditis elegans
S16	VLGSRSVGKSS	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S180	SQGKSS-CSVM	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
S180	AENNNK-CSIM	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S180	DDGKP--CSIS	1	Caenorhabditis elegans
S180	PPGDGKGCVIA	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S20	RSVGKSSLTIQ	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
S20	RNVGKTTLTVR	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S20	PHVGKSALVLR	1	Caenorhabditis elegans
S20	RSVGKSSLTVQ	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S21	SVGKSSLTIQF	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
S21	NVGKTTLTVRF	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S21	HVGKSALVLRF	1	Caenorhabditis elegans
S21	SVGKSSLTVQY	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S34	GQFVDSYDPTI	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
S34	SRFVESYYPTI	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S34	NIFPERYESTI	1	Caenorhabditis elegans
S34	NHFVESYYPTI	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
T38	DSYDPTIENTF	3	Homo sapiens, Mus musculus, Rattus norvegicus
T38	ESYYPTIENEF	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
T38	ERYESTIEDQH	1	Caenorhabditis elegans
T38	ESYYPTIENTF	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
T38	DSYDPTIKNTF	1	Bos taurus
V17	LGYRSVGKSSL	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
V17	IGARNVGKTTL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V17	MGYPHVGKSAL	1	Caenorhabditis elegans
V17	LGSRSVGKSSL	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V32	VEGQFVDSYDP	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
V32	VESRFVESYYP	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V32	TQNIFPERYES	1	Caenorhabditis elegans
V32	VENHFVESYYP	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y35	QFVDSYDPTIE	3	Homo sapiens, Mus musculus, Rattus norvegicus
Y35	RFVESYYPTIE	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Y35	IFPERYESTIE	1	Caenorhabditis elegans
Y35	HFVESYYPTIE	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y35	QFVDSYDPTIK	1	Bos taurus