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: MAP3K11

Gene summary for MAP3K11

Gene summary.

Gene information	Species	Human
	Gene symbol	MAP3K11
	Gene ID	4296
	Gene name	mitogen-activated protein kinase kinase kinase 11
	Gene Alias	MEKK11
	Cytomap	11q13.1
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	A0A024R5E6

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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
4296	MAP3K11	LZE8T	Human	Esophagus	ESCC	2.18e-05	8.49e-02	0.067
4296	MAP3K11	LZE20T	Human	Esophagus	ESCC	1.02e-14	8.25e-01	0.0662
4296	MAP3K11	LZE22D1	Human	Esophagus	HGIN	1.90e-02	9.61e-02	0.0595
4296	MAP3K11	LZE22T	Human	Esophagus	ESCC	3.91e-03	4.10e-01	0.068
4296	MAP3K11	LZE24T	Human	Esophagus	ESCC	2.10e-19	5.60e-01	0.0596
4296	MAP3K11	P1T-E	Human	Esophagus	ESCC	1.98e-10	8.84e-01	0.0875
4296	MAP3K11	P2T-E	Human	Esophagus	ESCC	7.07e-29	4.11e-01	0.1177
4296	MAP3K11	P4T-E	Human	Esophagus	ESCC	4.27e-16	5.25e-01	0.1323
4296	MAP3K11	P5T-E	Human	Esophagus	ESCC	7.72e-17	2.82e-01	0.1327
4296	MAP3K11	P8T-E	Human	Esophagus	ESCC	6.54e-34	6.17e-01	0.0889
4296	MAP3K11	P9T-E	Human	Esophagus	ESCC	1.53e-10	3.31e-01	0.1131
4296	MAP3K11	P10T-E	Human	Esophagus	ESCC	3.99e-27	5.65e-01	0.116
4296	MAP3K11	P11T-E	Human	Esophagus	ESCC	3.66e-09	6.12e-01	0.1426
4296	MAP3K11	P12T-E	Human	Esophagus	ESCC	9.61e-23	4.10e-01	0.1122
4296	MAP3K11	P15T-E	Human	Esophagus	ESCC	1.93e-17	5.16e-01	0.1149
4296	MAP3K11	P16T-E	Human	Esophagus	ESCC	8.75e-22	4.45e-01	0.1153
4296	MAP3K11	P17T-E	Human	Esophagus	ESCC	1.02e-05	4.93e-01	0.1278
4296	MAP3K11	P19T-E	Human	Esophagus	ESCC	6.84e-03	5.93e-01	0.1662
4296	MAP3K11	P20T-E	Human	Esophagus	ESCC	5.10e-15	3.38e-01	0.1124
4296	MAP3K11	P21T-E	Human	Esophagus	ESCC	3.24e-35	5.87e-01	0.1617

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:007099727	Esophagus	HGIN	neuron death	81/2587	361/18723	5.01e-06	1.61e-04	81
GO:190121424	Esophagus	HGIN	regulation of neuron death	68/2587	319/18723	1.46e-04	2.91e-03	68
GO:190121625	Esophagus	HGIN	positive regulation of neuron death	27/2587	97/18723	2.16e-04	3.96e-03	27
GO:00448437	Esophagus	HGIN	cell cycle G1/S phase transition	52/2587	241/18723	6.19e-04	8.58e-03	52
GO:005140219	Esophagus	HGIN	neuron apoptotic process	52/2587	246/18723	1.01e-03	1.26e-02	52
GO:004352520	Esophagus	HGIN	positive regulation of neuron apoptotic process	17/2587	58/18723	1.64e-03	1.82e-02	17
GO:007190016	Esophagus	ESCC	regulation of protein serine/threonine kinase activity	227/8552	359/18723	1.12e-11	4.10e-10	227
GO:0070997111	Esophagus	ESCC	neuron death	216/8552	361/18723	3.49e-08	6.45e-07	216
GO:003109818	Esophagus	ESCC	stress-activated protein kinase signaling cascade	154/8552	247/18723	8.53e-08	1.44e-06	154
GO:005140318	Esophagus	ESCC	stress-activated MAPK cascade	147/8552	239/18723	5.43e-07	7.18e-06	147
GO:004484314	Esophagus	ESCC	cell cycle G1/S phase transition	148/8552	241/18723	5.68e-07	7.48e-06	148
GO:00719029	Esophagus	ESCC	positive regulation of protein serine/threonine kinase activity	124/8552	200/18723	2.27e-06	2.61e-05	124
GO:004677710	Esophagus	ESCC	protein autophosphorylation	138/8552	227/18723	2.98e-06	3.38e-05	138
GO:0051402110	Esophagus	ESCC	neuron apoptotic process	148/8552	246/18723	3.08e-06	3.47e-05	148
GO:1901214111	Esophagus	ESCC	regulation of neuron death	186/8552	319/18723	3.35e-06	3.73e-05	186
GO:004586018	Esophagus	ESCC	positive regulation of protein kinase activity	219/8552	386/18723	6.91e-06	6.97e-05	219
GO:003367420	Esophagus	ESCC	positive regulation of kinase activity	260/8552	467/18723	7.26e-06	7.22e-05	260
GO:007030217	Esophagus	ESCC	regulation of stress-activated protein kinase signaling cascade	119/8552	195/18723	1.07e-05	1.01e-04	119
GO:1901216111	Esophagus	ESCC	positive regulation of neuron death	65/8552	97/18723	1.76e-05	1.56e-04	65
GO:003287217	Esophagus	ESCC	regulation of stress-activated MAPK cascade	116/8552	192/18723	2.63e-05	2.21e-04	116

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0493230	Esophagus	HGIN	Non-alcoholic fatty liver disease	66/1383	155/8465	5.21e-15	1.21e-13	9.64e-14	66
hsa04932113	Esophagus	HGIN	Non-alcoholic fatty liver disease	66/1383	155/8465	5.21e-15	1.21e-13	9.64e-14	66
hsa04932210	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0493238	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0493222	Liver	Cirrhotic	Non-alcoholic fatty liver disease	106/2530	155/8465	2.16e-23	2.40e-21	1.48e-21	106
hsa0493232	Liver	Cirrhotic	Non-alcoholic fatty liver disease	106/2530	155/8465	2.16e-23	2.40e-21	1.48e-21	106
hsa0493242	Liver	HCC	Non-alcoholic fatty liver disease	124/4020	155/8465	4.54e-17	2.54e-15	1.41e-15	124
hsa0493252	Liver	HCC	Non-alcoholic fatty liver disease	124/4020	155/8465	4.54e-17	2.54e-15	1.41e-15	124
hsa0493228	Oral cavity	OSCC	Non-alcoholic fatty liver disease	124/3704	155/8465	1.22e-20	1.37e-18	6.96e-19	124
hsa0401014	Oral cavity	OSCC	MAPK signaling pathway	165/3704	302/8465	7.11e-05	2.74e-04	1.40e-04	165
hsa04932112	Oral cavity	OSCC	Non-alcoholic fatty liver disease	124/3704	155/8465	1.22e-20	1.37e-18	6.96e-19	124
hsa0401015	Oral cavity	OSCC	MAPK signaling pathway	165/3704	302/8465	7.11e-05	2.74e-04	1.40e-04	165
hsa0493229	Oral cavity	LP	Non-alcoholic fatty liver disease	101/2418	155/8465	1.53e-21	6.37e-20	4.10e-20	101
hsa0493237	Oral cavity	LP	Non-alcoholic fatty liver disease	101/2418	155/8465	1.53e-21	6.37e-20	4.10e-20	101

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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

MAP3K11

SNV

Missense_Mutation

rs760824405

c.1552N>A

p.Glu518Lys

p.E518K

Q16584

protein_coding

tolerated(0.37)

benign(0.223)

TCGA-A2-A04W-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MAP3K11

SNV

Missense_Mutation

rs758769421

c.451G>A

p.Asp151Asn

p.D151N

Q16584

protein_coding

deleterious(0.03)

probably_damaging(0.93)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

MAP3K11

SNV

Missense_Mutation

rs779565351

c.2006N>A

p.Arg669His

p.R669H

Q16584

protein_coding

deleterious(0.04)

benign(0)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAP3K11

deletion

Frame_Shift_Del

c.2471delN

p.Gly824AlafsTer123

p.G824Afs*123

Q16584

protein_coding

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAP3K11

SNV

Missense_Mutation

novel

c.496N>T

p.Arg166Trp

p.R166W

Q16584

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-C5-A7X5-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

MAP3K11

SNV

Missense_Mutation

novel

c.553G>A

p.Glu185Lys

p.E185K

Q16584

protein_coding

tolerated(0.66)

benign(0.055)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

MAP3K11

SNV

Missense_Mutation

novel

c.32N>A

p.Ser11Asn

p.S11N

Q16584

protein_coding

deleterious_low_confidence(0.01)

benign(0.431)

TCGA-VS-A8EC-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

carboplatin

MAP3K11

SNV

Missense_Mutation

rs756165003

c.328N>A

p.Glu110Lys

p.E110K

Q16584

protein_coding

deleterious(0.04)

benign(0.129)

TCGA-VS-A953-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP3K11

SNV

Missense_Mutation

rs569473618

c.2240G>A

p.Arg747His

p.R747H

Q16584

protein_coding

deleterious_low_confidence(0.05)

benign(0.374)

TCGA-A6-5661-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MAP3K11

SNV

Missense_Mutation

c.656N>T

p.Ala219Val

p.A219V

Q16584

protein_coding

deleterious(0)

probably_damaging(0.936)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<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
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	249565853	CEP-1347
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	CHEMBL290352	CEP-1347
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	249565875
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	249565786
4296	MAP3K11	SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		CEP-1347	CEP-1347	24044867

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