Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: NR3C1

Gene summary for NR3C1

Gene summary.

Gene information	Species	Human
	Gene symbol	NR3C1
	Gene ID	2908
	Gene name	nuclear receptor subfamily 3 group C member 1
	Gene Alias	GCCR
	Cytomap	5q31.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	F1D8N4

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
2908	NR3C1	LZE4T	Human	Esophagus	ESCC	2.55e-13	5.23e-01	0.0811
2908	NR3C1	LZE7T	Human	Esophagus	ESCC	3.09e-05	7.67e-01	0.0667
2908	NR3C1	LZE20T	Human	Esophagus	ESCC	6.26e-03	2.32e-01	0.0662
2908	NR3C1	LZE22T	Human	Esophagus	ESCC	5.03e-05	4.27e-01	0.068
2908	NR3C1	LZE24T	Human	Esophagus	ESCC	7.16e-29	9.92e-01	0.0596
2908	NR3C1	LZE21T	Human	Esophagus	ESCC	2.47e-02	2.29e-01	0.0655
2908	NR3C1	LZE6T	Human	Esophagus	ESCC	7.34e-09	6.26e-01	0.0845
2908	NR3C1	P2T-E	Human	Esophagus	ESCC	8.53e-15	3.71e-01	0.1177
2908	NR3C1	P4T-E	Human	Esophagus	ESCC	6.91e-19	5.15e-01	0.1323
2908	NR3C1	P5T-E	Human	Esophagus	ESCC	7.40e-34	7.44e-01	0.1327
2908	NR3C1	P8T-E	Human	Esophagus	ESCC	2.89e-19	5.02e-01	0.0889
2908	NR3C1	P9T-E	Human	Esophagus	ESCC	9.57e-23	4.88e-01	0.1131
2908	NR3C1	P10T-E	Human	Esophagus	ESCC	4.58e-19	3.77e-01	0.116
2908	NR3C1	P11T-E	Human	Esophagus	ESCC	2.00e-14	8.76e-01	0.1426
2908	NR3C1	P12T-E	Human	Esophagus	ESCC	1.57e-56	1.18e+00	0.1122
2908	NR3C1	P15T-E	Human	Esophagus	ESCC	2.78e-34	8.99e-01	0.1149
2908	NR3C1	P16T-E	Human	Esophagus	ESCC	1.55e-11	1.88e-01	0.1153
2908	NR3C1	P17T-E	Human	Esophagus	ESCC	1.99e-07	6.01e-01	0.1278
2908	NR3C1	P19T-E	Human	Esophagus	ESCC	1.51e-07	7.20e-01	0.1662
2908	NR3C1	P20T-E	Human	Esophagus	ESCC	8.07e-43	1.17e+00	0.1124

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:000705911	Esophagus	ESCC	chromosome segregation	238/8552	346/18723	1.72e-18	1.82e-16	238
GO:0030522110	Esophagus	ESCC	intracellular receptor signaling pathway	170/8552	265/18723	8.58e-10	2.09e-08	170
GO:0048545111	Esophagus	ESCC	response to steroid hormone	204/8552	339/18723	4.47e-08	8.11e-07	204
GO:000632517	Esophagus	ESCC	chromatin organization	240/8552	409/18723	6.52e-08	1.14e-06	240
GO:00715599	Esophagus	ESCC	response to transforming growth factor beta	157/8552	256/18723	2.95e-07	4.23e-06	157
GO:0071383110	Esophagus	ESCC	cellular response to steroid hormone stimulus	127/8552	204/18723	1.26e-06	1.55e-05	127
GO:00715609	Esophagus	ESCC	cellular response to transforming growth factor beta stimulus	151/8552	250/18723	1.78e-06	2.10e-05	151
GO:003051819	Esophagus	ESCC	intracellular steroid hormone receptor signaling pathway	76/8552	116/18723	1.25e-05	1.15e-04	76
GO:004340119	Esophagus	ESCC	steroid hormone mediated signaling pathway	87/8552	136/18723	1.25e-05	1.15e-04	87
GO:1901654111	Esophagus	ESCC	response to ketone	118/8552	194/18723	1.45e-05	1.31e-04	118
GO:19016556	Esophagus	ESCC	cellular response to ketone	59/8552	96/18723	1.32e-03	6.30e-03	59
GO:003196020	Esophagus	ESCC	response to corticosteroid	95/8552	167/18723	2.27e-03	9.99e-03	95
GO:005138420	Esophagus	ESCC	response to glucocorticoid	85/8552	148/18723	2.60e-03	1.11e-02	85
GO:000975516	Esophagus	ESCC	hormone-mediated signaling pathway	106/8552	190/18723	3.13e-03	1.30e-02	106
GO:00715487	Esophagus	ESCC	response to dexamethasone	26/8552	39/18723	6.63e-03	2.43e-02	26
GO:00319582	Esophagus	ESCC	corticosteroid receptor signaling pathway	12/8552	15/18723	7.31e-03	2.63e-02	12
GO:00429212	Esophagus	ESCC	glucocorticoid receptor signaling pathway	11/8552	14/18723	1.30e-02	4.27e-02	11
GO:00713849	Esophagus	ESCC	cellular response to corticosteroid stimulus	37/8552	61/18723	1.32e-02	4.31e-02	37
GO:00485457	Liver	NAFLD	response to steroid hormone	75/1882	339/18723	3.44e-11	1.12e-08	75
GO:00713836	Liver	NAFLD	cellular response to steroid hormone stimulus	48/1882	204/18723	1.50e-08	1.83e-06	48

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
NR3C1	ADIPO	Colorectum	ADJ	ZC3HAV1,SLC7A5,PRKAR2B, etc.	6.53e-02
NR3C1	PERI	Colorectum	CRC	ZC3HAV1,SLC7A5,PRKAR2B, etc.	1.60e-01
NR3C1	PERI	Colorectum	FAP	ZC3HAV1,SLC7A5,PRKAR2B, etc.	5.44e-02
NR3C1	CFIB	Colorectum	Healthy	ZC3HAV1,SLC7A5,PRKAR2B, etc.	2.12e-01
NR3C1	PERI	Colorectum	Healthy	ZC3HAV1,SLC7A5,PRKAR2B, etc.	6.84e-02
NR3C1	AT2L	Lung	IAC	IRF4,IL3RA,SESN3, etc.	4.90e-01
NR3C1	BAS	Oral cavity	LP	CALCRL,RUNX3,LDLRAD4, etc.	1.23e-01
NR3C1	PERI	Prostate	BPH	GPR183,RUBCN,SLC15A4, etc.	3.57e-01
NR3C1	PERI	Prostate	Healthy	GPR183,RUBCN,SLC15A4, etc.	2.40e-01

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

NR3C1

SNV

Missense_Mutation

c.251N>G

p.Leu84Arg

p.L84R

P04150

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(1)

TCGA-BH-A1F8-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

NR3C1

SNV

Missense_Mutation

c.905G>T

p.Cys302Phe

p.C302F

P04150

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

NR3C1

SNV

Missense_Mutation

rs761295829

c.1688N>T

p.Thr563Met

p.T563M

P04150

protein_coding

deleterious(0)

possibly_damaging(0.897)

TCGA-E2-A1LB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NR3C1

insertion

In_Frame_Ins

novel

c.709_710insATATCCATTTTAGTTGTGAAGGAAAATATAAAAATG

p.Leu237delinsTyrIleHisPheSerCysGluGlyLysTyrLysAsnVal

p.L237delinsYIHFSCEGKYKNV

P04150

protein_coding

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NR3C1

SNV

Missense_Mutation

c.574G>C

p.Asp192His

p.D192H

P04150

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NR3C1

SNV

Missense_Mutation

rs756635644

c.341N>T

p.Ser114Leu

p.S114L

P04150

protein_coding

tolerated_low_confidence(0.78)

possibly_damaging(0.664)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NR3C1

SNV

Missense_Mutation

c.248N>T

p.Ser83Leu

p.S83L

P04150

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.998)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NR3C1

SNV

Missense_Mutation

c.157N>G

p.Gln53Glu

p.Q53E

P04150

protein_coding

tolerated_low_confidence(0.17)

benign(0.006)

TCGA-LP-A4AV-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NR3C1

SNV

Missense_Mutation

novel

c.179N>C

p.Arg60Thr

p.R60T

P04150

protein_coding

tolerated_low_confidence(0.22)

benign(0.003)

TCGA-VS-A954-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

NR3C1

SNV

Missense_Mutation

rs750359967

c.1031A>G

p.Gln344Arg

p.Q344R

P04150

protein_coding

tolerated(0.08)

benign(0.353)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR		Mifepristone	MIFEPRISTONE
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR		BUDESONIDE	BUDESONIDE
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR	agonist	CHEMBL1200376	BETAMETHASONE BENZOATE
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR		ORG 34517/34850
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR	agonist	178103646	DESOXIMETASONE
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR	agonist	CHEMBL1200844	METHYLPREDNISOLONE ACETATE
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR		TPI-1020
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR		CHRYSIN	CHRYSIN	19592245
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR		HYDROCORTAMATE	HYDROCORTAMATE
2908	NR3C1	DRUGGABLE GENOME, NUCLEAR HORMONE RECEPTOR, ENZYME, TRANSCRIPTION FACTOR		E-GUGGULSTERONE	E-GUGGULSTERONE

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