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: RNF19A

Gene summary for RNF19A

Gene summary.

Gene information	Species	Human
	Gene symbol	RNF19A
	Gene ID	25897
	Gene name	ring finger protein 19A, RBR E3 ubiquitin protein ligase
	Gene Alias	RNF19
	Cytomap	8q22.2
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	Q9NV58

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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
25897	RNF19A	GSM4909287	Human	Breast	IDC	2.73e-13	5.79e-01	0.2057
25897	RNF19A	GSM4909290	Human	Breast	IDC	1.09e-11	4.67e-01	0.2096
25897	RNF19A	GSM4909298	Human	Breast	IDC	1.87e-18	4.96e-01	0.1551
25897	RNF19A	GSM4909311	Human	Breast	IDC	3.32e-09	-1.52e-01	0.1534
25897	RNF19A	GSM4909317	Human	Breast	IDC	3.00e-10	3.94e-01	0.1355
25897	RNF19A	GSM4909319	Human	Breast	IDC	6.97e-12	-8.05e-02	0.1563
25897	RNF19A	GSM4909321	Human	Breast	IDC	2.92e-03	-1.25e-01	0.1559
25897	RNF19A	M1	Human	Breast	IDC	1.36e-36	1.00e+00	0.1577
25897	RNF19A	NCCBC6	Human	Breast	DCIS	4.22e-02	4.85e-01	0.2095
25897	RNF19A	P1	Human	Breast	IDC	5.14e-12	5.12e-01	0.1527
25897	RNF19A	DCIS2	Human	Breast	DCIS	9.80e-45	2.91e-01	0.0085
25897	RNF19A	CA_HPV_1	Human	Cervix	CC	2.00e-02	2.41e-02	0.0264
25897	RNF19A	CCI_2	Human	Cervix	CC	3.27e-05	1.65e+00	0.5249
25897	RNF19A	CCI_3	Human	Cervix	CC	3.25e-03	6.43e-01	0.516
25897	RNF19A	HTA11_3410_2000001011	Human	Colorectum	AD	1.43e-10	-4.45e-01	0.0155
25897	RNF19A	HTA11_3361_2000001011	Human	Colorectum	AD	8.96e-04	-5.19e-01	-0.1207
25897	RNF19A	HTA11_83_2000001011	Human	Colorectum	SER	3.43e-03	-3.93e-01	-0.1526
25897	RNF19A	HTA11_696_2000001011	Human	Colorectum	AD	7.30e-16	-5.07e-01	-0.1464
25897	RNF19A	HTA11_866_2000001011	Human	Colorectum	AD	1.32e-03	-3.02e-01	-0.1001
25897	RNF19A	HTA11_5212_2000001011	Human	Colorectum	AD	1.02e-02	-5.95e-01	-0.2061

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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
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
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:004586214	Breast	IDC	positive regulation of proteolysis	66/1434	372/18723	9.76e-11	1.29e-08	66
GO:001049814	Breast	IDC	proteasomal protein catabolic process	75/1434	490/18723	5.59e-09	4.41e-07	75
GO:004217614	Breast	IDC	regulation of protein catabolic process	63/1434	391/18723	1.32e-08	9.61e-07	63
GO:190336214	Breast	IDC	regulation of cellular protein catabolic process	46/1434	255/18723	4.00e-08	2.68e-06	46
GO:190305014	Breast	IDC	regulation of proteolysis involved in cellular protein catabolic process	41/1434	221/18723	9.77e-08	5.84e-06	41
GO:006113614	Breast	IDC	regulation of proteasomal protein catabolic process	33/1434	187/18723	5.24e-06	1.75e-04	33
GO:190336414	Breast	IDC	positive regulation of cellular protein catabolic process	29/1434	155/18723	5.93e-06	1.90e-04	29
GO:200005814	Breast	IDC	regulation of ubiquitin-dependent protein catabolic process	30/1434	164/18723	6.62e-06	2.05e-04	30
GO:004316114	Breast	IDC	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1434	412/18723	9.55e-06	2.68e-04	57
GO:004573214	Breast	IDC	positive regulation of protein catabolic process	37/1434	231/18723	1.46e-05	3.71e-04	37
GO:190305213	Breast	IDC	positive regulation of proteolysis involved in cellular protein catabolic process	25/1434	133/18723	2.34e-05	5.59e-04	25
GO:190180014	Breast	IDC	positive regulation of proteasomal protein catabolic process	22/1434	114/18723	4.68e-05	1.04e-03	22
GO:000989614	Breast	IDC	positive regulation of catabolic process	62/1434	492/18723	7.06e-05	1.42e-03	62
GO:003243414	Breast	IDC	regulation of proteasomal ubiquitin-dependent protein catabolic process	24/1434	134/18723	7.59e-05	1.50e-03	24
GO:00324368	Breast	IDC	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	18/1434	90/18723	1.39e-04	2.48e-03	18
GO:20000609	Breast	IDC	positive regulation of ubiquitin-dependent protein catabolic process	20/1434	107/18723	1.61e-04	2.76e-03	20
GO:003133114	Breast	IDC	positive regulation of cellular catabolic process	54/1434	427/18723	1.85e-04	3.07e-03	54
GO:004586224	Breast	DCIS	positive regulation of proteolysis	65/1390	372/18723	7.13e-11	9.17e-09	65
GO:001049824	Breast	DCIS	proteasomal protein catabolic process	75/1390	490/18723	1.44e-09	1.40e-07	75
GO:004217624	Breast	DCIS	regulation of protein catabolic process	62/1390	391/18723	9.98e-09	7.53e-07	62

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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

RNF19A

SNV

Missense_Mutation

c.254N>C

p.Asn85Thr

p.N85T

Q9NV58

protein_coding

tolerated_low_confidence(0.37)

benign(0)

TCGA-A2-A0EX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RNF19A

SNV

Missense_Mutation

novel

c.1550N>T

p.Ala517Val

p.A517V

Q9NV58

protein_coding

tolerated(0.39)

benign(0.012)

TCGA-A2-A3XY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RNF19A

SNV

Missense_Mutation

novel

c.1554N>G

p.Ser518Arg

p.S518R

Q9NV58

protein_coding

deleterious(0.04)

possibly_damaging(0.723)

TCGA-A8-A07B-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF19A

SNV

Missense_Mutation

novel

c.95T>G

p.Met32Arg

p.M32R

Q9NV58

protein_coding

deleterious_low_confidence(0.01)

benign(0.202)

TCGA-A8-A09A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RNF19A

SNV

Missense_Mutation

c.1756N>G

p.Thr586Ala

p.T586A

Q9NV58

protein_coding

tolerated(0.39)

benign(0.251)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

RNF19A

SNV

Missense_Mutation

c.1515G>C

p.Glu505Asp

p.E505D

Q9NV58

protein_coding

tolerated(0.23)

benign(0.005)

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

RNF19A

SNV

Missense_Mutation

c.1771N>A

p.Ala591Thr

p.A591T

Q9NV58

protein_coding

deleterious(0.04)

benign(0.368)

TCGA-GM-A2DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

RNF19A

insertion

Nonsense_Mutation

novel

c.2024_2025insGTTACCCAAACTGCTTCCTGTTCAGAAGTTTCACAGTTGAATCATAT

p.Ser675ArgfsTer14

p.S675Rfs*14

Q9NV58

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

RNF19A

insertion

Nonsense_Mutation

novel

c.686_687insCACTTGCCGAAAGTGTTTTTAAGTGCATTTCTATCCCAGA

p.Ala230ThrfsTer7

p.A230Tfs*7

Q9NV58

protein_coding

TCGA-A8-A090-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RNF19A

SNV

Missense_Mutation

c.1586G>A

p.Arg529Gln

p.R529Q

Q9NV58

protein_coding

tolerated(0.2)

possibly_damaging(0.652)

TCGA-C5-A1BK-01

Cervix

cervical & endocervical cancer

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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