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: FANCA

Gene summary for FANCA

Gene summary.

Gene information	Species	Human
	Gene symbol	FANCA
	Gene ID	2175
	Gene name	FA complementation group A
	Gene Alias	FA
	Cytomap	16q24.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	O15360

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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
2175	FANCA	C43	Human	Oral cavity	OSCC	2.98e-19	2.81e-01	0.1704
2175	FANCA	C46	Human	Oral cavity	OSCC	1.24e-18	3.63e-01	0.1673
2175	FANCA	C51	Human	Oral cavity	OSCC	8.26e-09	3.52e-01	0.2674
2175	FANCA	C57	Human	Oral cavity	OSCC	3.15e-07	2.06e-01	0.1679
2175	FANCA	C08	Human	Oral cavity	OSCC	6.87e-07	2.20e-01	0.1919
2175	FANCA	LN22	Human	Oral cavity	OSCC	6.01e-09	6.83e-01	0.1733
2175	FANCA	LN46	Human	Oral cavity	OSCC	8.31e-13	3.23e-01	0.1666
2175	FANCA	LP17	Human	Oral cavity	LP	3.06e-04	2.85e-01	0.2349
2175	FANCA	SYSMH2	Human	Oral cavity	OSCC	1.80e-04	1.50e-01	0.2326
2175	FANCA	SYSMH3	Human	Oral cavity	OSCC	3.06e-15	2.86e-01	0.2442
2175	FANCA	SYSMH5	Human	Oral cavity	OSCC	1.65e-05	1.76e-01	0.0647
2175	FANCA	ATC12	Human	Thyroid	ATC	5.43e-04	1.41e-01	0.34
2175	FANCA	ATC13	Human	Thyroid	ATC	1.28e-06	1.66e-01	0.34
2175	FANCA	ATC2	Human	Thyroid	ATC	3.71e-05	5.01e-01	0.34
2175	FANCA	ATC4	Human	Thyroid	ATC	8.62e-06	1.80e-01	0.34
2175	FANCA	ATC5	Human	Thyroid	ATC	1.24e-09	2.14e-01	0.34

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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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:00421108	Cervix	CC	T cell activation	107/2311	487/18723	1.24e-09	1.46e-07	107
GO:00508638	Cervix	CC	regulation of T cell activation	80/2311	329/18723	1.28e-09	1.47e-07	80
GO:190370610	Cervix	CC	regulation of hemopoiesis	80/2311	367/18723	2.14e-07	9.55e-06	80
GO:00614588	Cervix	CC	reproductive system development	87/2311	427/18723	1.37e-06	4.55e-05	87
GO:00486088	Cervix	CC	reproductive structure development	86/2311	424/18723	1.90e-06	5.97e-05	86
GO:00510904	Cervix	CC	regulation of DNA-binding transcription factor activity	87/2311	440/18723	4.85e-06	1.22e-04	87
GO:19021056	Cervix	CC	regulation of leukocyte differentiation	61/2311	279/18723	5.16e-06	1.29e-04	61
GO:00507273	Cervix	CC	regulation of inflammatory response	75/2311	386/18723	3.95e-05	6.18e-04	75
GO:0045580	Cervix	CC	regulation of T cell differentiation	33/2311	146/18723	3.75e-04	3.87e-03	33
GO:00302173	Cervix	CC	T cell differentiation	51/2311	257/18723	3.81e-04	3.89e-03	51
GO:19031314	Cervix	CC	mononuclear cell differentiation	76/2311	426/18723	5.66e-04	5.42e-03	76
GO:00456192	Cervix	CC	regulation of lymphocyte differentiation	37/2311	174/18723	6.06e-04	5.69e-03	37
GO:0045589	Cervix	CC	regulation of regulatory T cell differentiation	9/2311	28/18723	5.02e-03	2.98e-02	9
GO:00300981	Cervix	CC	lymphocyte differentiation	63/2311	374/18723	6.21e-03	3.52e-02	63
GO:00482851	Cervix	CC	organelle fission	78/2311	488/18723	9.70e-03	4.79e-02	78
GO:0045066	Cervix	CC	regulatory T cell differentiation	9/2311	31/18723	1.04e-02	4.97e-02	9
GO:004211013	Cervix	HSIL_HPV	T cell activation	48/737	487/18723	5.12e-09	7.61e-07	48
GO:005072711	Cervix	HSIL_HPV	regulation of inflammatory response	41/737	386/18723	8.30e-09	1.03e-06	41
GO:005086312	Cervix	HSIL_HPV	regulation of T cell activation	37/737	329/18723	9.84e-09	1.19e-06	37
GO:190370613	Cervix	HSIL_HPV	regulation of hemopoiesis	35/737	367/18723	1.35e-06	6.21e-05	35

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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

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗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

FANCA

SNV

Missense_Mutation

c.502C>G

p.Gln168Glu

p.Q168E

O15360

protein_coding

deleterious(0.03)

benign(0.006)

TCGA-A8-A09I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

FANCA

SNV

Missense_Mutation

c.2791N>C

p.Asp931His

p.D931H

O15360

protein_coding

deleterious(0)

probably_damaging(0.963)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FANCA

SNV

Missense_Mutation

c.112N>A

p.Glu38Lys

p.E38K

O15360

protein_coding

tolerated(0.15)

benign(0.272)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FANCA

SNV

Missense_Mutation

rs376103033

c.3157N>T

p.Arg1053Cys

p.R1053C

O15360

protein_coding

tolerated(0.23)

benign(0.015)

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

FANCA

SNV

Missense_Mutation

rs764206631

c.3250N>T

p.Arg1084Cys

p.R1084C

O15360

protein_coding

tolerated(0.07)

benign(0.003)

TCGA-AR-A0TR-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

FANCA

SNV

Missense_Mutation

c.3043G>A

p.Glu1015Lys

p.E1015K

O15360

protein_coding

tolerated(0.74)

benign(0.003)

TCGA-BH-A1EO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FANCA

SNV

Missense_Mutation

c.2080N>T

p.Asp694Tyr

p.D694Y

O15360

protein_coding

tolerated(0.06)

possibly_damaging(0.819)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FANCA

SNV

Missense_Mutation

c.155N>T

p.Arg52Leu

p.R52L

O15360

protein_coding

tolerated(0.06)

possibly_damaging(0.468)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

FANCA

insertion

Nonsense_Mutation

novel

c.3409_3410insTCTTCCATGAGTGTGGGTAATAAAT

p.Gly1137ValfsTer7

p.G1137Vfs*7

O15360

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

FANCA

insertion

Nonsense_Mutation

novel

c.3130_3131insTGAGAGTCTGAGCCCTTGGGA

p.Gln1044delinsLeuArgValTerAlaLeuGlyLys

p.Q1044delinsLRV*ALGK

O15360

protein_coding

TCGA-A2-A0CM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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
2175	FANCA	CLINICALLY ACTIONABLE, DNA REPAIR		CISPLATIN	CISPLATIN	26181256

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