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: MYO19

Gene summary for MYO19

Gene summary.

Gene information	Species	Human
	Gene symbol	MYO19
	Gene ID	80179
	Gene name	myosin XIX
	Gene Alias	MYOHD1
	Cytomap	17q12
	Gene Type	protein-coding
	GO ID	GO:0000266
	UniProtAcc	A0A024R0S9

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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
80179	MYO19	P2_cSCC	Human	Skin	cSCC	2.09e-16	5.35e-01	-0.024
80179	MYO19	P4_cSCC	Human	Skin	cSCC	1.17e-20	5.26e-01	-0.00290000000000005
80179	MYO19	P10_cSCC	Human	Skin	cSCC	1.10e-12	4.38e-01	0.1017
80179	MYO19	male-WTA	Human	Thyroid	PTC	6.70e-05	7.44e-02	0.1037
80179	MYO19	PTC01	Human	Thyroid	PTC	2.52e-02	5.59e-02	0.1899
80179	MYO19	PTC04	Human	Thyroid	PTC	7.07e-09	1.41e-01	0.1927
80179	MYO19	PTC05	Human	Thyroid	PTC	8.10e-12	5.06e-01	0.2065
80179	MYO19	PTC06	Human	Thyroid	PTC	3.70e-15	3.98e-01	0.2057
80179	MYO19	PTC07	Human	Thyroid	PTC	2.92e-06	1.59e-01	0.2044
80179	MYO19	ATC09	Human	Thyroid	ATC	7.16e-07	1.91e-01	0.2871
80179	MYO19	ATC11	Human	Thyroid	ATC	4.11e-05	4.47e-01	0.3386
80179	MYO19	ATC12	Human	Thyroid	ATC	4.53e-18	3.40e-01	0.34
80179	MYO19	ATC13	Human	Thyroid	ATC	8.42e-15	2.51e-01	0.34
80179	MYO19	ATC1	Human	Thyroid	ATC	3.87e-05	1.79e-01	0.2878
80179	MYO19	ATC2	Human	Thyroid	ATC	2.07e-09	7.22e-01	0.34
80179	MYO19	ATC3	Human	Thyroid	ATC	2.55e-06	4.70e-01	0.338
80179	MYO19	ATC4	Human	Thyroid	ATC	2.72e-21	4.21e-01	0.34
80179	MYO19	ATC5	Human	Thyroid	ATC	1.82e-14	2.85e-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
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:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:00516567	Cervix	CC	establishment of organelle localization	76/2311	390/18723	3.17e-05	5.21e-04	76
GO:00108218	Cervix	CC	regulation of mitochondrion organization	34/2311	144/18723	1.27e-04	1.58e-03	34
GO:00513021	Cervix	CC	regulation of cell division	39/2311	177/18723	2.05e-04	2.33e-03	39
GO:00009107	Cervix	CC	cytokinesis	37/2311	173/18723	5.40e-04	5.23e-03	37
GO:00300487	Cervix	CC	actin filament-based movement	29/2311	127/18723	6.91e-04	6.33e-03	29
GO:00307057	Cervix	CC	cytoskeleton-dependent intracellular transport	40/2311	195/18723	7.92e-04	6.99e-03	40
GO:0032465	Cervix	CC	regulation of cytokinesis	22/2311	92/18723	1.55e-03	1.20e-02	22
GO:00516541	Cervix	CC	establishment of mitochondrion localization	10/2311	29/18723	1.74e-03	1.31e-02	10
GO:00995157	Cervix	CC	actin filament-based transport	8/2311	21/18723	2.44e-03	1.71e-02	8
GO:00300507	Cervix	CC	vesicle transport along actin filament	7/2311	19/18723	5.65e-03	3.25e-02	7
GO:00516461	Cervix	CC	mitochondrion localization	13/2311	50/18723	6.42e-03	3.58e-02	13
GO:00482851	Cervix	CC	organelle fission	78/2311	488/18723	9.70e-03	4.79e-02	78
GO:005165616	Esophagus	HGIN	establishment of organelle localization	90/2587	390/18723	4.27e-07	1.94e-05	90
GO:001082119	Esophagus	HGIN	regulation of mitochondrion organization	42/2587	144/18723	1.20e-06	4.68e-05	42
GO:000091015	Esophagus	HGIN	cytokinesis	44/2587	173/18723	3.26e-05	8.32e-04	44
GO:003070517	Esophagus	HGIN	cytoskeleton-dependent intracellular transport	45/2587	195/18723	3.07e-04	5.15e-03	45
GO:005165010	Esophagus	HGIN	establishment of vesicle localization	35/2587	161/18723	3.89e-03	3.54e-02	35
GO:00516542	Esophagus	HGIN	establishment of mitochondrion localization	10/2587	29/18723	4.07e-03	3.65e-02	10
GO:005164810	Esophagus	HGIN	vesicle localization	37/2587	177/18723	6.03e-03	4.87e-02	37

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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

MYO19

SNV

Missense_Mutation

rs532830674

c.2585G>A

p.Arg862His

p.R862H

Q96H55

protein_coding

tolerated(0.17)

benign(0.012)

TCGA-A8-A096-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYO19

SNV

Missense_Mutation

rs765344804

c.2794N>T

p.Arg932Trp

p.R932W

Q96H55

protein_coding

deleterious(0.03)

benign(0.332)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

MYO19

insertion

Frame_Shift_Ins

novel

c.2809_2810insTGGT

p.Cys937LeufsTer4

p.C937Lfs*4

Q96H55

protein_coding

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MYO19

insertion

Frame_Shift_Ins

novel

c.2807_2808insTTCCGCATTAAATGCAGTAACAGATACCAGTT

p.Cys937SerfsTer33

p.C937Sfs*33

Q96H55

protein_coding

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MYO19

SNV

Missense_Mutation

novel

c.2006N>G

p.Tyr669Cys

p.Y669C

Q96H55

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MYO19

SNV

Missense_Mutation

novel

c.1691N>G

p.Asp564Gly

p.D564G

Q96H55

protein_coding

tolerated(0.25)

possibly_damaging(0.87)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MYO19

SNV

Missense_Mutation

novel

c.1588N>A

p.Val530Met

p.V530M

Q96H55

protein_coding

tolerated(0.14)

benign(0.022)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MYO19

SNV

Missense_Mutation

rs369381777

c.584N>A

p.Arg195His

p.R195H

Q96H55

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MYO19

SNV

Missense_Mutation

rs766865716

c.670N>G

p.Arg224Gly

p.R224G

Q96H55

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MYO19

SNV

Missense_Mutation

rs776257543

c.2270G>A

p.Arg757His

p.R757H

Q96H55

protein_coding

deleterious(0)

probably_damaging(0.915)

TCGA-EK-A3GK-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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