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 PTPN22

Gene summary

Basic gene Info.	Gene symbol	PTPN22
	Gene name	protein tyrosine phosphatase, non-receptor type 22 (lymphoid)
	Synonyms	LYP\|LYP1\|LYP2\|PEP\|PTPN8
	Cytomap	UCSC genome browser: 1p13.2
	Type of gene	protein-coding
	RefGenes	NM_001193431.1, NM_012411.4,NM_015967.5,
	Description	PEST-domain phosphatasehematopoietic cell protein-tyrosine phosphatase 70Z-PEPlymphoid phosphataselymphoid-specific protein tyrosine phosphataseprotein tyrosine phosphatase, non-receptor type 8tyrosine-protein phosphatase non-receptor type 22
	Modification date	20141222
dbXrefs	MIM : 600716
	HGNC : HGNC
	Ensembl : ENSG00000134242
	HPRD : 06100
	Vega : OTTHUMG00000011936
Protein	UniProt: Q9Y2R2 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PTPN22
	BioGPS: 26191
Pathway	NCI Pathway Interaction Database: PTPN22
	KEGG: PTPN22
	REACTOME: PTPN22
	Pathway Commons: PTPN22
Context	iHOP: PTPN22
	ligand binding site mutation search in PubMed: PTPN22
	UCL Cancer Institute: PTPN22
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
GO:0006470	protein dephosphorylation	10068674
GO:0032817	regulation of natural killer cell proliferation	20522204
GO:0035335	peptidyl-tyrosine dephosphorylation	10068674
GO:0050860	negative regulation of T cell receptor signaling pathway	18056643

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Ligand binding site mutations for PTPN22

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
Q278	Y279C	COAD	1
G230	G230S	HNSC	1
K191,H189	Y190C	HNSC	1
K53	K53N	UCEC	1
K191	K191N	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 PTPN22

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
G230	G230S	-1.4708377
H189	Y190C	-1.2235822
K191	Y190C	-1.2235822
K191	K191N	-1.1144342
K53	K53N	-0.9004656
Q278	Y279C	-0.48724603

(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 PTPN22 from PDB

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Differential gene expression and gene-gene network for PTPN22

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 PTPN22 and the right PPI network was created from samples without mutations in the LBS of PTPN22. 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 PTPN22

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0004364	Autoimmune Diseases	149	Biomarker, GeneticVariation
umls:C0003873	Arthritis, Rheumatoid	137	Biomarker, GeneticVariation
umls:C0011854	Diabetes Mellitus, Type 1	119	Biomarker, GeneticVariation
umls:C0024141	Lupus Erythematosus, Systemic	45	Biomarker, GeneticVariation
umls:C0018213	Graves Disease	21	Biomarker, GeneticVariation
umls:C0021390	Inflammatory Bowel Diseases	10	Biomarker, GeneticVariation
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 PTPN22

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

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PTPN22 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
III		Peptide ligand (TYR,GLY,GLU,GLU,TYR,ASP,ASP,LEU,TYR)	3olr	A	G230
III		Peptide ligand (TYR,GLY,GLU,GLU,TYR,ASP,ASP,LEU)	3olr	B	G230
III		Peptide ligand (TYR,GLY,GLU,GLU,TYR,ASP,ASP,LEU,TYR)	3olr	C	G230
III		Peptide ligand (ASP,GLY,GLU,GLU,TYR,ASP,ASP,PRO,PHE)	3omh	A	G230
III		Peptide ligand (ASP,GLY,GLU,GLU,TYR,ASP,ASP,PRO,PHE)	3omh	C	G230
III		Peptide ligand (ASP,GLY,GLU,GLU,TYR,ASP,ASP,PRO)	3omh	D	G230
PO4		PHOSPHATE ION	3h2x	A	H189 K191
PO4		PHOSPHATE ION	3h2x	A	K53
N75		3-[(3-CHLOROPHENYL)ETHYNYL]-2-{4-[2-(CYCLOPROPYLAMINO)- 2-OXOETHOXY]PHENYL}-6-HYDROXY-1-BENZOFURAN-5- CARBOXYLIC ACID	4j51	A	Q278
N75		3-[(3-CHLOROPHENYL)ETHYNYL]-2-{4-[2-(CYCLOPROPYLAMINO)- 2-OXOETHOXY]PHENYL}-6-HYDROXY-1-BENZOFURAN-5- CARBOXYLIC ACID	4j51	B	Q278

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Conservation information for LBS of PTPN22

Multiple alignments for Q9Y2R2 in multiple species

LBS

AA sequence

# species

Species