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: RBFOX2

Gene summary for RBFOX2

Gene summary.

Gene information	Species	Human
	Gene symbol	RBFOX2
	Gene ID	23543
	Gene name	RNA binding fox-1 homolog 2
	Gene Alias	FOX2
	Cytomap	22q12.3
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	O43251

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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
23543	RBFOX2	CA_HPV_3	Human	Cervix	CC	4.95e-04	1.70e-01	0.0414
23543	RBFOX2	CCI_1	Human	Cervix	CC	7.99e-16	1.70e+00	0.528
23543	RBFOX2	CCI_2	Human	Cervix	CC	2.32e-10	1.25e+00	0.5249
23543	RBFOX2	CCI_3	Human	Cervix	CC	1.03e-24	1.37e+00	0.516
23543	RBFOX2	sample3	Human	Cervix	CC	4.63e-06	2.08e-01	0.1387
23543	RBFOX2	T3	Human	Cervix	CC	4.77e-04	1.92e-01	0.1389
23543	RBFOX2	HTA11_3410_2000001011	Human	Colorectum	AD	1.28e-41	1.22e+00	0.0155
23543	RBFOX2	HTA11_2487_2000001011	Human	Colorectum	SER	8.55e-37	2.23e+00	-0.1808
23543	RBFOX2	HTA11_2951_2000001011	Human	Colorectum	AD	1.23e-32	2.85e+00	0.0216
23543	RBFOX2	HTA11_1938_2000001011	Human	Colorectum	AD	5.35e-37	2.30e+00	-0.0811
23543	RBFOX2	HTA11_78_2000001011	Human	Colorectum	AD	8.14e-11	7.39e-01	-0.1088
23543	RBFOX2	HTA11_347_2000001011	Human	Colorectum	AD	9.79e-43	2.28e+00	-0.1954
23543	RBFOX2	HTA11_411_2000001011	Human	Colorectum	SER	3.88e-34	2.91e+00	-0.2602
23543	RBFOX2	HTA11_2112_2000001011	Human	Colorectum	SER	4.42e-20	2.32e+00	-0.2196
23543	RBFOX2	HTA11_3361_2000001011	Human	Colorectum	AD	2.94e-33	2.64e+00	-0.1207
23543	RBFOX2	HTA11_83_2000001011	Human	Colorectum	SER	5.46e-33	2.16e+00	-0.1526
23543	RBFOX2	HTA11_696_2000001011	Human	Colorectum	AD	1.85e-67	2.73e+00	-0.1464
23543	RBFOX2	HTA11_866_2000001011	Human	Colorectum	AD	9.98e-51	2.51e+00	-0.1001
23543	RBFOX2	HTA11_1391_2000001011	Human	Colorectum	AD	2.30e-47	2.97e+00	-0.059
23543	RBFOX2	HTA11_2992_2000001011	Human	Colorectum	SER	1.28e-35	2.51e+00	-0.1706

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:003052012	Prostate	Tumor	intracellular estrogen receptor signaling pathway	18/3246	54/18723	3.26e-03	1.70e-02	18
GO:000838027	Skin	AK	RNA splicing	111/1910	434/18723	1.85e-20	5.49e-17	111
GO:190331125	Skin	AK	regulation of mRNA metabolic process	81/1910	288/18723	7.27e-18	8.61e-15	81
GO:004348428	Skin	AK	regulation of RNA splicing	54/1910	148/18723	9.66e-18	9.53e-15	54
GO:000037526	Skin	AK	RNA splicing, via transesterification reactions	85/1910	324/18723	1.16e-16	7.62e-14	85
GO:000037726	Skin	AK	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	84/1910	320/18723	1.69e-16	9.11e-14	84
GO:000039826	Skin	AK	mRNA splicing, via spliceosome	84/1910	320/18723	1.69e-16	9.11e-14	84
GO:005068420	Skin	AK	regulation of mRNA processing	47/1910	137/18723	1.92e-14	7.57e-12	47
GO:004802427	Skin	AK	regulation of mRNA splicing, via spliceosome	39/1910	101/18723	3.87e-14	1.43e-11	39
GO:000038020	Skin	AK	alternative mRNA splicing, via spliceosome	30/1910	77/18723	2.57e-11	4.90e-09	30
GO:004854528	Skin	AK	response to steroid hormone	73/1910	339/18723	4.51e-10	5.24e-08	73
GO:000038120	Skin	AK	regulation of alternative mRNA splicing, via spliceosome	23/1910	60/18723	7.70e-09	5.12e-07	23
GO:003009928	Skin	AK	myeloid cell differentiation	72/1910	381/18723	1.76e-07	7.28e-06	72
GO:007138326	Skin	AK	cellular response to steroid hormone stimulus	46/1910	204/18723	1.79e-07	7.37e-06	46
GO:003052226	Skin	AK	intracellular receptor signaling pathway	55/1910	265/18723	2.26e-07	9.03e-06	55
GO:004887228	Skin	AK	homeostasis of number of cells	56/1910	272/18723	2.33e-07	9.18e-06	56
GO:003410128	Skin	AK	erythrocyte homeostasis	33/1910	129/18723	4.75e-07	1.74e-05	33
GO:001635817	Skin	AK	dendrite development	49/1910	243/18723	2.42e-06	6.72e-05	49
GO:000226228	Skin	AK	myeloid cell homeostasis	36/1910	157/18723	2.48e-06	6.76e-05	36
GO:190370625	Skin	AK	regulation of hemopoiesis	65/1910	367/18723	6.74e-06	1.52e-04	65

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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
RBFOX2	NUER	Prostate	ADJ	PPP1R12B,CHD9,DHX8, etc.	0.00e+00
RBFOX2	BAS	Prostate	ADJ	PPP1R12B,CHD9,DHX8, etc.	0.00e+00
RBFOX2	BAS	Prostate	Tumor	PPP1R12B,CHD9,DHX8, etc.	8.56e-03
RBFOX2	NUER	Prostate	Tumor	PPP1R12B,CHD9,DHX8, etc.	7.36e-03

∗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

RBFOX2

SNV

Missense_Mutation

c.964A>G

p.Ser322Gly

p.S322G

O43251

protein_coding

tolerated_low_confidence(0.31)

benign(0.015)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RBFOX2

SNV

Missense_Mutation

novel

c.383N>C

p.Asn128Thr

p.N128T

O43251

protein_coding

tolerated(0.93)

benign(0.019)

TCGA-D8-A1XG-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

RBFOX2

SNV

Missense_Mutation

c.434N>T

p.Ser145Leu

p.S145L

O43251

protein_coding

deleterious(0.04)

benign(0.015)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RBFOX2

SNV

Missense_Mutation

novel

c.383N>C

p.Asn128Thr

p.N128T

O43251

protein_coding

tolerated(0.93)

benign(0.019)

TCGA-E9-A1RE-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

RBFOX2

insertion

Frame_Shift_Ins

novel

c.547_548insTTTAT

p.Arg183LeufsTer29

p.R183Lfs*29

O43251

protein_coding

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

RBFOX2

insertion

Nonsense_Mutation

novel

c.546_547insGCATTACGATGATAGGATTGCAGATTAT

p.Arg183AlafsTer4

p.R183Afs*4

O43251

protein_coding

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

RBFOX2

SNV

Missense_Mutation

c.1073G>A

p.Arg358Gln

p.R358Q

O43251

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

RBFOX2

SNV

Missense_Mutation

novel

c.511N>C

p.Ser171Arg

p.S171R

O43251

protein_coding

tolerated(0.3)

benign(0.147)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

RBFOX2

SNV

Missense_Mutation

c.1018N>A

p.Ala340Thr

p.A340T

O43251

protein_coding

tolerated(0.06)

benign(0.154)

TCGA-AA-3877-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

RBFOX2

SNV

Missense_Mutation

novel

c.292N>T

p.Ile98Phe

p.I98F

O43251

protein_coding

tolerated_low_confidence(0.09)

possibly_damaging(0.791)

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

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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

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