mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

Home

	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 RORC

Gene summary

Basic gene Info.	Gene symbol	RORC
	Gene name	RAR-related orphan receptor C
	Synonyms	NR1F3\|RORG\|RZR-GAMMA\|RZRG\|TOR
	Cytomap	UCSC genome browser: 1q21
	Type of gene	protein-coding
	RefGenes	NM_001001523.1, NM_005060.3,
	Description	RAR-related orphan nuclear receptor variant 2nuclear receptor ROR-gammanuclear receptor RZR-gammanuclear receptor subfamily 1 group F member 3retinoic acid-binding receptor gammaretinoid-related orphan receptor gamma
	Modification date	20141207
dbXrefs	MIM : 602943
	HGNC : HGNC
	Ensembl : ENSG00000143365
	HPRD : 04250
	Vega : OTTHUMG00000013053
Protein	UniProt: P51449 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_RORC
	BioGPS: 6097
Pathway	NCI Pathway Interaction Database: RORC
	KEGG: RORC
	REACTOME: RORC
	Pathway Commons: RORC
Context	iHOP: RORC
	ligand binding site mutation search in PubMed: RORC
	UCL Cancer Institute: RORC
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:0036315	cellular response to sterol	19965867

Top

Ligand binding site mutations for RORC

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
S12	E14K	BRCA	1
C285	E283K	BRCA	1
V493,Q495	V494F	COAD	1
L396	E395K	HNSC	1
R367	R367W	KIRC	1
F54	G53S	OV	1
F401	F401L	SKCM	1
S12	E14D	SKCM	1
V376	R374C	STAD	1
R367	R367W	STAD	1
I397	S398N	STAD	1
V376	R374C	UCEC	1
C393	C393Y	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.

Top

Protein structure related information for RORC

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
F401	F401L	-1.1177184
I397	S398N	-0.99087138
V376	R374C	-0.8354408
C285	E283K	-0.79557912
F54	G53S	-0.67759537
L396	E395K	-0.58870128
R367	R367W	-0.56648779
C393	C393Y	-0.52166967
V493	V494F	-0.31862931
Q495	V494F	-0.31862931
S12	E14D	-0.29537021
S12	E14K	-0.2351761

(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 RORC from PDB

Top

Differential gene expression and gene-gene network for RORC

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 RORC and the right PPI network was created from samples without mutations in the LBS of RORC. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.

Top

Phenotype information for RORC

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0021368	Inflammation	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

Top

Pharmacological information for RORC

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 RORC go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
NBH		N-(4-{[BENZYL(PROPYL)AMINO]METHYL}PHENYL)-2-[4- (ETHYLSULFONYL)PHENYL]ACETAMIDE	4nie	A	C285 R367
NBH		N-(4-{[BENZYL(PROPYL)AMINO]METHYL}PHENYL)-2-[4- (ETHYLSULFONYL)PHENYL]ACETAMIDE	4nie	B	C285 R367
3QQ		N-(4-FLUOROBENZYL)-N-(2-METHYLPROPYL)-6-{[1- (METHYLSULFONYL)PIPERIDIN-4-YL]AMINO}PYRIDINE-3- SULFONAMIDE	4wlb	B	C285 R367 L396 F401
43V		N-[4-(2,5-DICHLOROPHENYL)-5-PHENYL-1,3-THIAZOL-2-YL]-2- [4-(ETHYLSULFONYL)PHENYL]ACETAMIDE	4xt9	A	C285 R367 V376 I397 F401
39K		N-(2-METHYLPROPYL)-N-({5-[4-(METHYLSULFONYL) PHENYL]THIOPHEN-2-YL}METHYL)-1- PHENYLMETHANESULFONAMIDE	4qm0	A	C285 R367 V376 L396 F401
4P3		6-CHLORO-4'-[(2-CHLORO-6-FLUOROBENZOYL)(METHYL)AMINO]- 3'-(2,2,2-TRIFLUOROETHOXY)BIPHENYL-3-CARBOXAMIDE	4zjr	A	C393 L396 I397 F401
4Q3		N-{4-[3-(ACETYLAMINO)-1-(PROPAN-2-YL)-1H-PYRAZOL-5-YL]- 2-[(1R,5S)-3-AZABICYCLO[3.1.0]HEX-3-YL]PHENYL}-2- CHLORO-6-FLUORO-N-METHYLBENZAMIDE	4zom	A	C393 L396 I397 F401
4Q3		N-{4-[3-(ACETYLAMINO)-1-(PROPAN-2-YL)-1H-PYRAZOL-5-YL]- 2-[(1R,5S)-3-AZABICYCLO[3.1.0]HEX-3-YL]PHENYL}-2- CHLORO-6-FLUORO-N-METHYLBENZAMIDE	4zom	B	C393 L396 I397 F401
4Q3		N-{4-[3-(ACETYLAMINO)-1-(PROPAN-2-YL)-1H-PYRAZOL-5-YL]- 2-[(1R,5S)-3-AZABICYCLO[3.1.0]HEX-3-YL]PHENYL}-2- CHLORO-6-FLUORO-N-METHYLBENZAMIDE	4zom	D	C393 L396 I397 F401
3SN		N-[4-(4-ACETYLPIPERAZIN-1-YL)-2-FLUOROBENZYL]-N- CYCLOBUTYLBENZENESULFONAMIDE	4wpf	D	I397 F401
VYI		N-(2-FLUOROPHENYL)-4-[(4-FLUOROPHENYL) SULFONYL]-2,3,4,5-TETRAHYDRO-1,4-BENZOXAZEPIN-6- AMINE	5aph	A	I397 F401
4P1		4-CHLORO-3-[1-(2-CHLORO-6-FLUOROBENZOYL)-1,2,3,4- TETRAHYDROQUINOLIN-6-YL]-N-METHYLBENZAMIDE	4zjw	A	L396
3SX		N-[4-(4-ACETYLPIPERAZIN-1-YL)BENZYL]-N-(2- METHYLPROPYL)-1-PHENYLMETHANESULFONAMIDE	4wqp	B	L396 F401
HC3		25-HYDROXYCHOLESTEROL	3l0l	A	L396 I397
HC3		25-HYDROXYCHOLESTEROL	3l0l	B	L396 I397
3SN		N-[4-(4-ACETYLPIPERAZIN-1-YL)-2-FLUOROBENZYL]-N- CYCLOBUTYLBENZENESULFONAMIDE	4wpf	A	L396 I397
39K		N-(2-METHYLPROPYL)-N-({5-[4-(METHYLSULFONYL) PHENYL]THIOPHEN-2-YL}METHYL)-1- PHENYLMETHANESULFONAMIDE	4qm0	C	L396 I397 F401
3SX		N-[4-(4-ACETYLPIPERAZIN-1-YL)BENZYL]-N-(2- METHYLPROPYL)-1-PHENYLMETHANESULFONAMIDE	4wqp	A	L396 I397 F401
4P3		6-CHLORO-4'-[(2-CHLORO-6-FLUOROBENZOYL)(METHYL)AMINO]- 3'-(2,2,2-TRIFLUOROETHOXY)BIPHENYL-3-CARBOXAMIDE	4zjr	D	L396 I397 F401
III		Peptide ligand (LYS,ILE,LEU,HIS,ARG,LEU,LEU,GLN,ASP,SER)	3l0l	A	Q495
III		Peptide ligand (GLU,LYS,HIS,LYS,ILE,LEU,HIS,ARG,LEU,LEU,GLN,ASP,SER)	3l0l	B	Q495
III		Peptide ligand (SER,LEU,LEU,LYS,LYS,LEU,LEU,ASP)	4wlb	A	Q495
III		Peptide ligand (SER,LEU,LEU,LYS,LYS,LEU,LEU,ASP)	4wlb	B	Q495
3QQ		N-(4-FLUOROBENZYL)-N-(2-METHYLPROPYL)-6-{[1- (METHYLSULFONYL)PIPERIDIN-4-YL]AMINO}PYRIDINE-3- SULFONAMIDE	4wlb	A	R367 L396 I397
DGX		DIGOXIN	3b0w	A	R367 V376 C393 L396
DGX		DIGOXIN	3b0w	B	R367 V376 L396
ZBD		4-{3-[4-(1,1,1,3,3,3-HEXAFLUORO-2-HYDROXYPROPAN-2-YL) BENZYL]-2,2-DIOXIDO-2,1,3-BENZOTHIADIAZOL-1(3H)-YL}-N- [(2R)-4-HYDROXYBUTAN-2-YL]-N-METHYLBUTANAMIDE	4ymq	A	R367 V376 L396 I397 F401
76E		2-CHLORO-6-FLUORO-N-[4-[3-(TRIFLUOROMETHYL) PHENYL]SULFONYL-3,5-DIHYDRO-2H-1,4- BENZOXAZEPIN-7-YL]BENZAMIDE	5apj	A	V376 C393 L396 I397
76E		2-CHLORO-6-FLUORO-N-[4-[3-(TRIFLUOROMETHYL) PHENYL]SULFONYL-3,5-DIHYDRO-2H-1,4- BENZOXAZEPIN-7-YL]BENZAMIDE	5apk	A	V376 C393 L396 I397
76E		2-CHLORO-6-FLUORO-N-[4-[3-(TRIFLUOROMETHYL) PHENYL]SULFONYL-3,5-DIHYDRO-2H-1,4- BENZOXAZEPIN-7-YL]BENZAMIDE	5apk	B	V376 C393 L396 I397
4P3		6-CHLORO-4'-[(2-CHLORO-6-FLUOROBENZOYL)(METHYL)AMINO]- 3'-(2,2,2-TRIFLUOROETHOXY)BIPHENYL-3-CARBOXAMIDE	4zjr	C	V376 C393 L396 I397 F401
4Q3		N-{4-[3-(ACETYLAMINO)-1-(PROPAN-2-YL)-1H-PYRAZOL-5-YL]- 2-[(1R,5S)-3-AZABICYCLO[3.1.0]HEX-3-YL]PHENYL}-2- CHLORO-6-FLUORO-N-METHYLBENZAMIDE	4zom	C	V376 C393 L396 I397 F401
HC2		20-HYDROXYCHOLESTEROL	3kyt	A	V376 I397
HC9		(3ALPHA,8ALPHA,22R)-CHOLEST-5-ENE-3,22-DIOL	3l0j	A	V376 I397
4D8	4ALPHA-CARBOXY-4BETA-METHYL-ZYMOSTEROL	(3BETA,4ALPHA,5BETA,14BETA)-3-HYDROXY-4-METHYLCHOLESTA- 8,24-DIENE-4-CARBOXYLIC ACID	4s14	A	V376 I397
4P3		6-CHLORO-4'-[(2-CHLORO-6-FLUOROBENZOYL)(METHYL)AMINO]- 3'-(2,2,2-TRIFLUOROETHOXY)BIPHENYL-3-CARBOXAMIDE	4zjr	B	V376 L396 I397
DMX		DIMETHYLBENZYLAMMONIUM PROPANE SULFONATE	4nie	A	V493
DMX		DIMETHYLBENZYLAMMONIUM PROPANE SULFONATE	4nie	B	V493

Top

Conservation information for LBS of RORC

Multiple alignments for P51449 in multiple species

LBS

AA sequence

# species

Species