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 FKBP5

Gene summary

Basic gene Info.	Gene symbol	FKBP5
	Gene name	FK506 binding protein 5
	Synonyms	AIG6\|FKBP51\|FKBP54\|P54\|PPIase\|Ptg-10
	Cytomap	UCSC genome browser: 6p21.31
	Type of gene	protein-coding
	RefGenes	NM_001145775.2, NM_001145776.1,NM_001145777.1,NM_004117.3,
	Description	51 kDa FK506-binding protein51 kDa FKBP54 kDa progesterone receptor-associated immunophilinFF1 antigenFKBP-51HSP90-binding immunophilinPPIase FKBP5T-cell FK506-binding proteinandrogen-regulated protein 6peptidyl-prolyl cis-trans isomerase FKBP5p
	Modification date	20141222
dbXrefs	MIM : 602623
	HGNC : HGNC
	Ensembl : ENSG00000096060
	HPRD : 04019
	Vega : OTTHUMG00000014576
Protein	UniProt: Q13451 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_FKBP5
	BioGPS: 2289
Pathway	NCI Pathway Interaction Database: FKBP5
	KEGG: FKBP5
	REACTOME: FKBP5
	Pathway Commons: FKBP5
Context	iHOP: FKBP5
	ligand binding site mutation search in PubMed: FKBP5
	UCL Cancer Institute: FKBP5
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:0000413	protein peptidyl-prolyl isomerization	11350175
GO:0061077	chaperone-mediated protein folding	11350175

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Ligand binding site mutations for FKBP5

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
I87	I87M	BLCA	1
S118	A116T	COAD	1
I122	I122M	COAD	1
T96	K98R	LUAD	1
A95	A95V	PRAD	1
G59	G59R	SKCM	1
T46	P47T	UCEC	1
Y57	H56N	UCEC	1
I122	S124L	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 FKBP5

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
S118	A116T	0.54379977
A95	A95V	0.53459133
I122	I122M	-1.3356534
Y57	H56N	-1.2197358
T46	P47T	-1.0624046
I87	I87M	-0.93488647
T96	K98R	-0.73500559
I122	S124L	-0.4118781
G59	G59R	-0.32964539

(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 FKBP5 from PDB

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Differential gene expression and gene-gene network for FKBP5

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 FKBP5 and the right PPI network was created from samples without mutations in the LBS of FKBP5. 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 FKBP5

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C1269683	Depressive Disorder, Major	13	Biomarker, GeneticVariation
umls:C0003873	Arthritis, Rheumatoid	2	Biomarker
umls:C0014175	Endometriosis	1	Biomarker
umls:C0021290	Infant, Newborn, Diseases	1	Biomarker
umls:C0525041	Neurobehavioral Manifestations	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for FKBP5

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 FKBP5 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
DMS		DIMETHYL SULFOXIDE	3o5q	A	I87
DMS		DIMETHYL SULFOXIDE	3o5q	A	T46 A95 T96
5B8		(1R)-3-(3,4-DIMETHOXYPHENYL)-1-{3-[2-(MORPHOLIN-4-YL) ETHOXY]PHENYL}PROPYL (2S)-1-[(2S,3R)-2-CYCLOHEXYL-3- HYDROXYBUTANOYL]PIPERIDINE-2-CARBOXYLATE	5dit	A	Y57 G59 I87 I122
37L		(3-{(1R)-3-(3,4-DIMETHOXYPHENYL)-1-[({(2S)-1-[(2S)-2- (3,4,5-TRIMETHOXYPHENYL)PENT-4-ENOYL]PIPERIDIN-2- YL}CARBONYL)OXY]PROPYL}PHENOXY)ACETIC ACID	4tw6	A	Y57 G59 I87 S118
37K		(1R)-3-(3,4-DIMETHOXYPHENYL)-1-{3-[2-(MORPHOLIN-4-YL) ETHOXY]PHENYL}PROPYL (2S)-1-[(2S)-2-[(1S)-CYCLOHEX-2- EN-1-YL]-2-(3,4,5-TRIMETHOXYPHENYL)ACETYL]PIPERIDINE- 2-CARBOXYLATE	4tw7	A	Y57 G59 I87 S118
1KZ		2-(3,4-DIMETHOXYPHENOXY)ETHYL (2S)-1-[(2-OXO-2,3- DIHYDRO-1,3-BENZOTHIAZOL-6-YL)SULFONYL]PIPERIDINE-2- CARBOXYLATE	4jfm	A	Y57 I87
FK5		TACROLIMUS (ANHYDROUS)	3o5r	A	Y57 I87 I122
RAP		RAPAMYCIN IMMUNOSUPPRESSANT DRUG	4drh	A	Y57 I87 I122
RAP		RAPAMYCIN IMMUNOSUPPRESSANT DRUG	4drh	D	Y57 I87 I122
RAP		RAPAMYCIN IMMUNOSUPPRESSANT DRUG	4dri	A	Y57 I87 I122
I63		{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-(3,3-DIMETHYL-2-OXOPENTANOYL)PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC ACID	4drk	A	Y57 I87 I122
I63		{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-(3,3-DIMETHYL-2-OXOPENTANOYL)PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC ACID	4drk	B	Y57 I87 I122
0MC		{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1S,2R)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC ACID	4drm	A	Y57 I87 I122
0MD		{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1R,2S)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC ACID	4dro	A	Y57 I87 I122
0MD		{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1R,2S)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC ACID	4drp	A	Y57 I87 I122
1KY		6-({(1S,5R)-3-[2-(3,4-DIMETHOXYPHENOXY)ETHYL]-2-OXO-3, 9-DIAZABICYCLO[3.3.1]NON-9-YL}SULFONYL)-1,3- BENZOTHIAZOL-2(3H)-ONE	4jfl	A	Y57 I87 I122
1KT		1-[(9S,13R,13AR)-1,3-DIMETHOXY-8-OXO-5,8,9,10,11,12,13, 13A-OCTAHYDRO-6H-9,13-EPIMINOAZOCINO[2,1- A]ISOQUINOLIN-14-YL]-2-(3,4,5-TRIMETHOXYPHENYL)ETHANE- 1,2-DIONE	4jfi	A	Y57 I87 S118
0MC		{3-[(1R)-3-(3,4-DIMETHOXYPHENYL)-1-({[(2S)-1-{[(1S,2R)-2-ETHYL-1-HYDROXYCYCLOHEXYL](OXO)ACETYL}PIPERIDIN-2-YL]CARBONYL}OXY)PROPYL]PHENOXY}ACETIC ACID	4drn	A	Y57 I87 S118 I122
0OS		{3-[(1S)-1-[({(2S)-1-[(3,5-DICHLOROPHENYL)SULFONYL]PIPERIDIN-2-YL}CARBONYL)OXY]-3-(3,4-DIMETHOXYPHENYL)PROPYL]PHENOXY}ACETIC ACID	4drq	A	Y57 I87 S118 I122
1KU		(1S,6R)-10-(1,3-BENZOTHIAZOL-6-YLSULFONYL)-3-[2-(3,4- DIMETHOXYPHENOXY)ETHYL]-3,10-DIAZABICYCLO[4.3.1]DECAN- 2-ONE	4jfj	A	Y57 I87 S118 I122
JFK		(1S,6R)-3-[2-(3,4-DIMETHOXYPHENOXY)ETHYL]-10-[(2-OXO-2, 3-DIHYDRO-1,3-BENZOTHIAZOL-6-YL)SULFONYL]-3,10- DIAZABICYCLO[4.3.1]DECAN-2-ONE	4jfk	A	Y57 I87 S118 I122
384		(1S,5S,6R)-10-[(3,5-DICHLOROPHENYL)SULFONYL]-5-(2- METHOXYETHOXY)-3-(2-METHOXYETHYL)-3,10- DIAZABICYCLO[4.3.1]DECAN-2-ONE	4tx0	A	Y57 I87 S118 I122

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Conservation information for LBS of FKBP5

Multiple alignments for Q13451 in multiple species

LBS

AA sequence

# species

Species