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 ADAMTS5

Gene summary

Basic gene Info.	Gene symbol	ADAMTS5
	Gene name	ADAM metallopeptidase with thrombospondin type 1 motif, 5
	Synonyms	ADAM-TS 11\|ADAM-TS 5\|ADAM-TS5\|ADAMTS-11\|ADAMTS-5\|ADAMTS11\|ADMP-2
	Cytomap	UCSC genome browser: 21q21.3
	Type of gene	protein-coding
	RefGenes	NM_007038.3,
	Description	A disintegrin and metalloproteinase with thrombospondin motifs 5a disintegrin and metalloproteinase with thrombospondin motifs 11a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 5 (aggrecanase-2)aggrecanase-2
	Modification date	20141222
dbXrefs	MIM : 605007
	HGNC : HGNC
	Ensembl : ENSG00000154736
	HPRD : 05420
	Vega : OTTHUMG00000078686
Protein	UniProt: Q9UNA0 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_ADAMTS5
	BioGPS: 11096
Pathway	NCI Pathway Interaction Database: ADAMTS5
	KEGG: ADAMTS5
	REACTOME: ADAMTS5
	Pathway Commons: ADAMTS5
Context	iHOP: ADAMTS5
	ligand binding site mutation search in PubMed: ADAMTS5
	UCL Cancer Institute: ADAMTS5
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

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Ligand binding site mutations for ADAMTS5

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
I446	D447V	BRCA	1
P476	R477Q	BRCA	1
L438	R437H	COAD	1
H403	A404V	COAD	1
P476	R477L	HNSC	1
D360	A362V	KIRC	1
P476	P476L	LUAD	1
D474	D474Y	LUAD	1
S445	S445C	LUAD	1
H420	H420N	LUAD	1
H403	A404E	LUAD	1
E398	E398D	SKCM	1
E411	E411K	STAD	1
D369	D369E	STAD	1
H373	H373Q	STAD	1
H373	G372E	UCEC	1
E411	E411K	UCEC	1
P476	R477Q	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 ADAMTS5

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
P476	R477Q	-1.4347621
L438	R437H	-1.4002307
E398	E398D	-1.0269045
D369	D369E	-1.010977
H373	H373Q	-0.84100945
P476	P476L	-0.83609627
P476	R477L	-0.82282381
H420	H420N	-0.82208638
D474	D474Y	-0.79274965
H373	G372E	-0.63957818
E411	E411K	-0.62235266
I446	D447V	-0.39483361
S445	S445C	-0.34112439
H403	A404E	-0.3271719
D360	A362V	-0.31997488
H403	A404V	-0.30250315

(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 ADAMTS5 from PDB

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Differential gene expression and gene-gene network for ADAMTS5

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 ADAMTS5 and the right PPI network was created from samples without mutations in the LBS of ADAMTS5. 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 ADAMTS5

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 ADAMTS5

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	DB03880	Batimastat	Small molecule
Experimental	DB06837	(2R)-N~4~-hydroxy-2-(3-hydroxybenzyl)-N~1~-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide	Small molecule
Experimental	DB06945	N-hydroxy-4-({4-[4-(trifluoromethyl)phenoxy]phenyl}sulfonyl)tetrahydro-2H-pyran-4-carboxamide	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of ADAMTS5 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
CA		CALCIUM(2+)	2rjq	A	D360 D474
CA		CALCIUM(2+)	3b8z	A	D360 D474
CA		CALCIUM(2+)	3b8z	B	D360 D474
CA		CALCIUM(2+)	3hy7	A	D360 D474
CA		CALCIUM(2+)	3hy7	B	D360 D474
CA		CALCIUM(2+)	3hy9	A	D360 D474
CA		CALCIUM(2+)	3hy9	B	D360 D474
CA		CALCIUM(2+)	3hyg	A	D360 D474
CA		CALCIUM(2+)	3hyg	B	D360 D474
CA		CALCIUM(2+)	3ljt	A	D360 D474
CA		CALCIUM(2+)	2rjq	A	D369 E398
CA		CALCIUM(2+)	3b8z	A	D369 E398
CA		CALCIUM(2+)	3b8z	B	D369 E398
CA		CALCIUM(2+)	3hy7	A	D369 E398
CA		CALCIUM(2+)	3hy7	B	D369 E398
CA		CALCIUM(2+)	3hy9	A	D369 E398
CA		CALCIUM(2+)	3hy9	B	D369 E398
CA		CALCIUM(2+)	3hyg	A	D369 E398
CA		CALCIUM(2+)	3hyg	B	D369 E398
CA		CALCIUM(2+)	3ljt	A	D369 E398
CA		CALCIUM(2+)	3b8z	A	D474
CA		CALCIUM(2+)	3b8z	B	D474
CA		CALCIUM(2+)	3hy7	A	D474
CA		CALCIUM(2+)	3hy7	B	D474
CA		CALCIUM(2+)	3hy9	A	D474
CA		CALCIUM(2+)	3hy9	B	D474
CA		CALCIUM(2+)	3hyg	A	D474
CA		CALCIUM(2+)	3hyg	B	D474
CA		CALCIUM(2+)	3ljt	A	D474 P476
BAT		BATIMASTAT	2rjq	A	E411 H420
097		MARIMASTAT	3hy7	A	E411 H420
097		MARIMASTAT	3hy7	B	E411 H420
098		(3R)-N~2~-(CYCLOPROPYLMETHYL)-N~1~-HYDROXY-3-(3-HYDROXYBENZYL)-N~4~-[(1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL]-L-ASPARTAMIDE	3hy9	B	E411 H420 L438
099		(2R)-N~4~-HYDROXY-2-(3-HYDROXYBENZYL)-N~1~-[(1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL]BUTANEDIAMIDE	3hyg	A	E411 H420 L438
099		(2R)-N~4~-HYDROXY-2-(3-HYDROXYBENZYL)-N~1~-[(1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL]BUTANEDIAMIDE	3hyg	B	E411 H420 L438
098		(3R)-N~2~-(CYCLOPROPYLMETHYL)-N~1~-HYDROXY-3-(3-HYDROXYBENZYL)-N~4~-[(1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL]-L-ASPARTAMIDE	3hy9	A	H373 E411 H420 L438
294		N-HYDROXY-4-({4-[4-(TRIFLUOROMETHYL)PHENOXY]PHENYL}SULFONYL)TETRAHYDRO-2H-PYRAN-4-CARBOXAMIDE	3b8z	A	H373 H403 E411 H420 L438 S445 I446
294		N-HYDROXY-4-({4-[4-(TRIFLUOROMETHYL)PHENOXY]PHENYL}SULFONYL)TETRAHYDRO-2H-PYRAN-4-CARBOXAMIDE	3b8z	B	H403 E411 H420 L438 I446
LA3		(R)-2-(4-(BENZO[D][1,3]DIOXOL-5-YL)BENZYL)-N4-HYDROXY-N1-((1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL)SUCCINAMIDE	3ljt	A	H403 E411 H420 L438 I446
ZN		ZINC(2+)	2rjq	A	H420
ZN		ZINC(2+)	3b8z	A	H420
ZN		ZINC(2+)	3b8z	B	H420
ZN		ZINC(2+)	3hy7	A	H420
ZN		ZINC(2+)	3hy7	B	H420
ZN		ZINC(2+)	3hy9	A	H420
ZN		ZINC(2+)	3hy9	B	H420
ZN		ZINC(2+)	3hyg	A	H420
ZN		ZINC(2+)	3hyg	B	H420
ZN		ZINC(2+)	3ljt	A	H420

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Conservation information for LBS of ADAMTS5

Multiple alignments for Q9UNA0 in multiple species

LBS

AA sequence

# species

Species