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: SFXN1

Gene summary for SFXN1

Gene summary.

Gene information	Species	Human
	Gene symbol	SFXN1
	Gene ID	94081
	Gene name	sideroflexin 1
	Gene Alias	SLC56A1
	Cytomap	5q35.2
	Gene Type	protein-coding
	GO ID	GO:0003333
	UniProtAcc	Q9H9B4

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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
94081	SFXN1	P126T-E	Human	Esophagus	ESCC	2.25e-07	5.80e-01	0.1125
94081	SFXN1	P127T-E	Human	Esophagus	ESCC	3.61e-12	5.55e-02	0.0826
94081	SFXN1	P128T-E	Human	Esophagus	ESCC	5.30e-13	2.06e-01	0.1241
94081	SFXN1	P130T-E	Human	Esophagus	ESCC	1.23e-21	5.05e-01	0.1676
94081	SFXN1	NAFLD1	Human	Liver	NAFLD	4.92e-05	6.40e-01	-0.04
94081	SFXN1	S43	Human	Liver	Cirrhotic	2.12e-06	-1.57e-01	-0.0187
94081	SFXN1	HCC1_Meng	Human	Liver	HCC	2.52e-70	3.90e-02	0.0246
94081	SFXN1	HCC2_Meng	Human	Liver	HCC	1.55e-15	-4.70e-02	0.0107
94081	SFXN1	HCC1	Human	Liver	HCC	4.08e-21	3.82e+00	0.5336
94081	SFXN1	HCC2	Human	Liver	HCC	8.14e-28	3.51e+00	0.5341
94081	SFXN1	HCC5	Human	Liver	HCC	1.14e-02	1.77e+00	0.4932
94081	SFXN1	Pt13.b	Human	Liver	HCC	2.26e-03	-5.55e-02	0.0251
94081	SFXN1	S014	Human	Liver	HCC	1.69e-14	6.83e-01	0.2254
94081	SFXN1	S015	Human	Liver	HCC	4.82e-16	9.65e-01	0.2375
94081	SFXN1	S016	Human	Liver	HCC	4.67e-17	7.50e-01	0.2243
94081	SFXN1	S027	Human	Liver	HCC	2.64e-02	3.75e-01	0.2446
94081	SFXN1	S028	Human	Liver	HCC	4.21e-03	3.44e-01	0.2503
94081	SFXN1	S029	Human	Liver	HCC	4.57e-11	6.54e-01	0.2581
94081	SFXN1	C04	Human	Oral cavity	OSCC	4.53e-16	9.11e-01	0.2633
94081	SFXN1	C21	Human	Oral cavity	OSCC	1.46e-33	1.14e+00	0.2678

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:0006839	Colorectum	AD	mitochondrial transport	102/3918	254/18723	1.87e-12	3.08e-10	102
GO:1990542	Colorectum	AD	mitochondrial transmembrane transport	47/3918	102/18723	1.09e-08	6.52e-07	47
GO:0006730	Colorectum	AD	one-carbon metabolic process	18/3918	40/18723	5.36e-04	5.74e-03	18
GO:19905423	Colorectum	FAP	mitochondrial transmembrane transport	29/2622	102/18723	1.09e-04	1.80e-03	29
GO:00068394	Colorectum	FAP	mitochondrial transport	55/2622	254/18723	5.58e-04	6.24e-03	55
GO:000683920	Esophagus	HGIN	mitochondrial transport	74/2587	254/18723	1.32e-10	1.32e-08	74
GO:199054220	Esophagus	HGIN	mitochondrial transmembrane transport	29/2587	102/18723	8.52e-05	1.87e-03	29
GO:0006839110	Esophagus	ESCC	mitochondrial transport	187/8552	254/18723	8.35e-20	9.81e-18	187
GO:1990542110	Esophagus	ESCC	mitochondrial transmembrane transport	72/8552	102/18723	2.94e-07	4.23e-06	72
GO:00068397	Liver	Cirrhotic	mitochondrial transport	112/4634	254/18723	1.03e-11	6.66e-10	112
GO:19905425	Liver	Cirrhotic	mitochondrial transmembrane transport	41/4634	102/18723	4.08e-04	3.37e-03	41
GO:00067303	Liver	Cirrhotic	one-carbon metabolic process	17/4634	40/18723	1.04e-02	4.61e-02	17
GO:000683912	Liver	HCC	mitochondrial transport	184/7958	254/18723	2.30e-22	3.83e-20	184
GO:199054212	Liver	HCC	mitochondrial transmembrane transport	78/7958	102/18723	2.73e-12	1.26e-10	78
GO:000683918	Oral cavity	OSCC	mitochondrial transport	162/7305	254/18723	8.96e-16	6.52e-14	162
GO:199054218	Oral cavity	OSCC	mitochondrial transmembrane transport	56/7305	102/18723	8.06e-04	4.32e-03	56
GO:0032329	Oral cavity	OSCC	serine transport	9/7305	11/18723	4.85e-03	1.92e-02	9
GO:000683927	Skin	cSCC	mitochondrial transport	124/4864	254/18723	3.54e-15	2.81e-13	124
GO:199054224	Skin	cSCC	mitochondrial transmembrane transport	43/4864	102/18723	2.68e-04	2.16e-03	43
GO:00067304	Skin	cSCC	one-carbon metabolic process	18/4864	40/18723	7.10e-03	3.40e-02	18

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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

SFXN1

SNV

Missense_Mutation

novel

c.785G>T

p.Trp262Leu

p.W262L

Q9H9B4

protein_coding

tolerated(0.2)

benign(0.007)

TCGA-AC-A5EH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SFXN1

insertion

In_Frame_Ins

novel

c.939_940insGCATTGCCACAAATGGTTTTTCCAACA

p.Leu313_Arg314insAlaLeuProGlnMetValPheProThr

p.L313_R314insALPQMVFPT

Q9H9B4

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

SFXN1

SNV

Missense_Mutation

c.671N>C

p.Gln224Pro

p.Q224P

Q9H9B4

protein_coding

tolerated(0.1)

possibly_damaging(0.811)

TCGA-EK-A2RN-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SFXN1

SNV

Missense_Mutation

c.158N>G

p.Asp53Gly

p.D53G

Q9H9B4

protein_coding

tolerated(0.23)

benign(0.102)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SFXN1

SNV

Missense_Mutation

rs374767128

c.475N>A

p.Val159Ile

p.V159I

Q9H9B4

protein_coding

deleterious(0.02)

possibly_damaging(0.474)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

SFXN1

SNV

Missense_Mutation

rs374767128

c.475N>A

p.Val159Ile

p.V159I

Q9H9B4

protein_coding

deleterious(0.02)

possibly_damaging(0.474)

TCGA-EI-6509-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

folfox

SFXN1

SNV

Missense_Mutation

novel

c.738N>A

p.Phe246Leu

p.F246L

Q9H9B4

protein_coding

tolerated(0.55)

benign(0.006)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SFXN1

SNV

Missense_Mutation

novel

c.897N>T

p.Glu299Asp

p.E299D

Q9H9B4

protein_coding

deleterious(0.02)

probably_damaging(1)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SFXN1

SNV

Missense_Mutation

novel

c.74N>T

p.Ala25Val

p.A25V

Q9H9B4

protein_coding

tolerated(0.41)

probably_damaging(0.938)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SFXN1

SNV

Missense_Mutation

novel

c.778N>C

p.Phe260Leu

p.F260L

Q9H9B4

protein_coding

tolerated(0.49)

benign(0.005)

TCGA-AP-A05O-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

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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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