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: RANBP1

Gene summary for RANBP1

Gene summary.

Gene information	Species	Human
	Gene symbol	RANBP1
	Gene ID	5902
	Gene name	RAN binding protein 1
	Gene Alias	HTF9A
	Cytomap	22q11.21
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	F6WQW2

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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
5902	RANBP1	GSM4909281	Human	Breast	IDC	5.56e-58	9.44e-01	0.21
5902	RANBP1	GSM4909282	Human	Breast	IDC	7.28e-61	9.74e-01	-0.0288
5902	RANBP1	GSM4909285	Human	Breast	IDC	2.26e-39	8.33e-01	0.21
5902	RANBP1	GSM4909286	Human	Breast	IDC	1.12e-07	3.65e-01	0.1081
5902	RANBP1	GSM4909287	Human	Breast	IDC	4.81e-17	5.11e-01	0.2057
5902	RANBP1	GSM4909288	Human	Breast	IDC	8.96e-16	6.61e-01	0.0988
5902	RANBP1	GSM4909290	Human	Breast	IDC	5.44e-07	4.59e-01	0.2096
5902	RANBP1	GSM4909291	Human	Breast	IDC	1.23e-09	5.01e-01	0.1753
5902	RANBP1	GSM4909294	Human	Breast	IDC	1.26e-08	2.79e-01	0.2022
5902	RANBP1	GSM4909296	Human	Breast	IDC	1.48e-14	9.11e-02	0.1524
5902	RANBP1	GSM4909297	Human	Breast	IDC	1.62e-11	6.64e-02	0.1517
5902	RANBP1	GSM4909298	Human	Breast	IDC	4.81e-13	4.69e-01	0.1551
5902	RANBP1	GSM4909304	Human	Breast	IDC	7.00e-03	2.95e-01	0.1636
5902	RANBP1	GSM4909311	Human	Breast	IDC	6.42e-31	-1.90e-01	0.1534
5902	RANBP1	GSM4909312	Human	Breast	IDC	4.66e-12	1.34e-02	0.1552
5902	RANBP1	GSM4909313	Human	Breast	IDC	3.56e-03	7.06e-02	0.0391
5902	RANBP1	GSM4909316	Human	Breast	IDC	3.63e-04	2.31e-01	0.21
5902	RANBP1	GSM4909318	Human	Breast	IDC	3.25e-13	7.08e-01	0.2031
5902	RANBP1	GSM4909319	Human	Breast	IDC	1.34e-40	-1.81e-01	0.1563
5902	RANBP1	GSM4909320	Human	Breast	IDC	1.95e-05	5.09e-02	0.1575

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:00725949	Cervix	CC	establishment of protein localization to organelle	99/2311	422/18723	1.23e-10	2.11e-08	99
GO:00069139	Cervix	CC	nucleocytoplasmic transport	71/2311	301/18723	4.04e-08	2.54e-06	71
GO:00511699	Cervix	CC	nuclear transport	71/2311	301/18723	4.04e-08	2.54e-06	71
GO:00345048	Cervix	CC	protein localization to nucleus	68/2311	290/18723	9.91e-08	5.25e-06	68
GO:00170388	Cervix	CC	protein import	48/2311	206/18723	8.62e-06	1.98e-04	48
GO:00511689	Cervix	CC	nuclear export	38/2311	154/18723	1.86e-05	3.46e-04	38
GO:00511707	Cervix	CC	import into nucleus	38/2311	159/18723	3.98e-05	6.18e-04	38
GO:00512368	Cervix	CC	establishment of RNA localization	39/2311	166/18723	4.76e-05	7.25e-04	39
GO:00066067	Cervix	CC	protein import into nucleus	37/2311	155/18723	5.13e-05	7.71e-04	37
GO:00506578	Cervix	CC	nucleic acid transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:00506588	Cervix	CC	RNA transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:000640310	Cervix	CC	RNA localization	43/2311	201/18723	2.00e-04	2.29e-03	43
GO:00510284	Cervix	CC	mRNA transport	31/2311	130/18723	2.05e-04	2.33e-03	31
GO:00066116	Cervix	CC	protein export from nucleus	17/2311	57/18723	3.61e-04	3.75e-03	17
GO:00159318	Cervix	CC	nucleobase-containing compound transport	43/2311	222/18723	1.72e-03	1.30e-02	43
GO:007259414	Cervix	HSIL_HPV	establishment of protein localization to organelle	29/737	422/18723	2.71e-03	2.58e-02	29
GO:003450412	Cervix	HSIL_HPV	protein localization to nucleus	21/737	290/18723	5.53e-03	4.45e-02	21
GO:0072594	Colorectum	AD	establishment of protein localization to organelle	148/3918	422/18723	7.95e-12	1.04e-09	148
GO:0006913	Colorectum	AD	nucleocytoplasmic transport	102/3918	301/18723	1.00e-07	4.85e-06	102
GO:0051169	Colorectum	AD	nuclear transport	102/3918	301/18723	1.00e-07	4.85e-06	102

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516618	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa052036	Breast	Precancer	Viral carcinogenesis	27/684	204/8465	7.19e-03	4.06e-02	3.11e-02	27
hsa0516619	Breast	Precancer	Human T-cell leukemia virus 1 infection	33/684	222/8465	4.29e-04	3.31e-03	2.53e-03	33
hsa0520312	Breast	Precancer	Viral carcinogenesis	27/684	204/8465	7.19e-03	4.06e-02	3.11e-02	27
hsa0516624	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0520322	Breast	IDC	Viral carcinogenesis	34/867	204/8465	2.82e-03	1.86e-02	1.39e-02	34
hsa0516634	Breast	IDC	Human T-cell leukemia virus 1 infection	40/867	222/8465	2.52e-04	2.21e-03	1.66e-03	40
hsa0520332	Breast	IDC	Viral carcinogenesis	34/867	204/8465	2.82e-03	1.86e-02	1.39e-02	34
hsa0516642	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa0520341	Breast	DCIS	Viral carcinogenesis	34/846	204/8465	1.88e-03	1.27e-02	9.33e-03	34
hsa0516652	Breast	DCIS	Human T-cell leukemia virus 1 infection	41/846	222/8465	7.03e-05	6.88e-04	5.07e-04	41
hsa052035	Breast	DCIS	Viral carcinogenesis	34/846	204/8465	1.88e-03	1.27e-02	9.33e-03	34
hsa05166	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72
hsa051661	Colorectum	AD	Human T-cell leukemia virus 1 infection	72/2092	222/8465	5.24e-03	2.44e-02	1.55e-02	72
hsa051662	Colorectum	MSS	Human T-cell leukemia virus 1 infection	68/1875	222/8465	1.84e-03	9.61e-03	5.89e-03	68
hsa051663	Colorectum	MSS	Human T-cell leukemia virus 1 infection	68/1875	222/8465	1.84e-03	9.61e-03	5.89e-03	68
hsa0516626	Endometrium	AEH	Human T-cell leukemia virus 1 infection	50/1197	222/8465	4.30e-04	3.11e-03	2.27e-03	50
hsa05166111	Endometrium	AEH	Human T-cell leukemia virus 1 infection	50/1197	222/8465	4.30e-04	3.11e-03	2.27e-03	50
hsa0516627	Endometrium	EEC	Human T-cell leukemia virus 1 infection	52/1237	222/8465	2.73e-04	2.36e-03	1.76e-03	52
hsa0516636	Endometrium	EEC	Human T-cell leukemia virus 1 infection	52/1237	222/8465	2.73e-04	2.36e-03	1.76e-03	52

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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

RANBP1

SNV

Missense_Mutation

novel

c.708N>T

p.Arg236Ser

p.R236S

protein_coding

deleterious(0)

possibly_damaging(0.565)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

RANBP1

SNV

Missense_Mutation

rs771917916

c.571N>A

p.Ala191Thr

p.A191T

protein_coding

tolerated(0.1)

possibly_damaging(0.85)

TCGA-F4-6856-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Ancillary

leucovorin

RANBP1

SNV

Missense_Mutation

novel

c.237N>T

p.Lys79Asn

p.K79N

protein_coding

tolerated_low_confidence(0.2)

benign(0.007)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

RANBP1

SNV

Missense_Mutation

novel

c.467N>G

p.Lys156Arg

p.K156R

protein_coding

tolerated(0.49)

benign(0.031)

TCGA-B5-A0K7-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RANBP1

SNV

Missense_Mutation

c.279N>T

p.Glu93Asp

p.E93D

protein_coding

tolerated(0.1)

benign(0.164)

TCGA-BS-A0UF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RANBP1

SNV

Missense_Mutation

novel

c.490N>T

p.Arg164Cys

p.R164C

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E6-A2P9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RANBP1

SNV

Missense_Mutation

c.305N>G

p.Pro102Arg

p.P102R

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-EY-A212-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

RANBP1

SNV

Missense_Mutation

rs756772977

c.764N>G

p.Glu255Gly

p.E255G

protein_coding

deleterious(0.01)

benign(0.356)

TCGA-EY-A5W2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RANBP1

SNV

Missense_Mutation

novel

c.385N>T

p.Arg129Trp

p.R129W

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

RANBP1

insertion

Frame_Shift_Ins

novel

c.469_470insTGCAGGTCTGCACTCTT

p.His157LeufsTer23

p.H157Lfs*23

protein_coding

TCGA-B5-A0K7-01

Endometrium

uterine corpus endometrioid carcinoma

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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