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: KDM5B

Gene summary for KDM5B

Gene summary.

Gene information	Species	Human
	Gene symbol	KDM5B
	Gene ID	10765
	Gene name	lysine demethylase 5B
	Gene Alias	CT31
	Cytomap	1q32.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q9UGL1

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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
10765	KDM5B	CA_HPV_1	Human	Cervix	CC	1.71e-08	-2.00e-01	0.0264
10765	KDM5B	CCI_1	Human	Cervix	CC	5.73e-05	8.64e-01	0.528
10765	KDM5B	CCI_3	Human	Cervix	CC	5.07e-08	9.45e-01	0.516
10765	KDM5B	sample3	Human	Cervix	CC	6.10e-04	3.15e-01	0.1387
10765	KDM5B	T3	Human	Cervix	CC	1.96e-03	3.37e-01	0.1389
10765	KDM5B	HTA11_347_2000001011	Human	Colorectum	AD	1.36e-04	4.77e-01	-0.1954
10765	KDM5B	HTA11_99999965104_69814	Human	Colorectum	MSS	3.03e-04	5.75e-01	0.281
10765	KDM5B	HTA11_99999974143_84620	Human	Colorectum	MSS	1.31e-03	-2.72e-01	0.3005
10765	KDM5B	F007	Human	Colorectum	FAP	7.26e-04	-2.39e-01	0.1176
10765	KDM5B	A002-C-010	Human	Colorectum	FAP	2.04e-02	-2.16e-01	0.242
10765	KDM5B	A001-C-207	Human	Colorectum	FAP	6.11e-07	-2.79e-01	0.1278
10765	KDM5B	A015-C-203	Human	Colorectum	FAP	2.07e-24	-4.22e-01	-0.1294
10765	KDM5B	A015-C-204	Human	Colorectum	FAP	1.18e-08	-2.95e-01	-0.0228
10765	KDM5B	A014-C-040	Human	Colorectum	FAP	7.89e-06	-4.85e-01	-0.1184
10765	KDM5B	A002-C-201	Human	Colorectum	FAP	4.10e-13	-2.01e-01	0.0324
10765	KDM5B	A002-C-203	Human	Colorectum	FAP	3.34e-03	-1.53e-01	0.2786
10765	KDM5B	A001-C-119	Human	Colorectum	FAP	5.07e-07	-9.85e-02	-0.1557
10765	KDM5B	A001-C-108	Human	Colorectum	FAP	4.49e-13	-1.76e-01	-0.0272
10765	KDM5B	A002-C-205	Human	Colorectum	FAP	5.39e-26	-3.50e-01	-0.1236
10765	KDM5B	A015-C-005	Human	Colorectum	FAP	3.79e-10	-3.84e-01	-0.0336

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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
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:0060444	Colorectum	MSS	branching involved in mammary gland duct morphogenesis	10/3467	22/18723	3.42e-03	2.56e-02	10
GO:0060603	Colorectum	MSS	mammary gland duct morphogenesis	12/3467	30/18723	5.00e-03	3.46e-02	12
GO:00108761	Colorectum	MSS	lipid localization	104/3467	448/18723	6.76e-03	4.38e-02	104
GO:0050678	Colorectum	MSS	regulation of epithelial cell proliferation	90/3467	381/18723	6.92e-03	4.45e-02	90
GO:00487324	Colorectum	FAP	gland development	103/2622	436/18723	3.61e-08	3.12e-06	103
GO:00485113	Colorectum	FAP	rhythmic process	72/2622	298/18723	1.67e-06	6.99e-05	72
GO:00605602	Colorectum	FAP	developmental growth involved in morphogenesis	58/2622	234/18723	7.21e-06	2.19e-04	58
GO:00226123	Colorectum	FAP	gland morphogenesis	34/2622	118/18723	2.13e-05	5.12e-04	34
GO:00605622	Colorectum	FAP	epithelial tube morphogenesis	71/2622	325/18723	7.23e-05	1.33e-03	71
GO:00165701	Colorectum	FAP	histone modification	94/2622	463/18723	1.06e-04	1.76e-03	94
GO:0023061	Colorectum	FAP	signal release	94/2622	463/18723	1.06e-04	1.76e-03	94
GO:00063253	Colorectum	FAP	chromatin organization	84/2622	409/18723	1.62e-04	2.47e-03	84
GO:00068691	Colorectum	FAP	lipid transport	81/2622	398/18723	2.84e-04	3.76e-03	81
GO:00614583	Colorectum	FAP	reproductive system development	85/2622	427/18723	4.30e-04	5.13e-03	85
GO:00097913	Colorectum	FAP	post-embryonic development	23/2622	80/18723	4.51e-04	5.32e-03	23
GO:00486083	Colorectum	FAP	reproductive structure development	84/2622	424/18723	5.40e-04	6.10e-03	84
GO:00017632	Colorectum	FAP	morphogenesis of a branching structure	44/2622	196/18723	8.79e-04	9.01e-03	44
GO:00308793	Colorectum	FAP	mammary gland development	33/2622	137/18723	1.07e-03	1.04e-02	33
GO:00506732	Colorectum	FAP	epithelial cell proliferation	84/2622	437/18723	1.39e-03	1.25e-02	84
GO:00108762	Colorectum	FAP	lipid localization	85/2622	448/18723	1.92e-03	1.63e-02	85

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
KDM5B	MES	Cervix	CC	AC016831.1,SNAPC1,ITPRID2, etc.	7.14e-01
KDM5B	CAF	Pancreas	ADJ	GPR137C,ZNF335,TCEAL5, etc.	7.22e-03
KDM5B	PSC	Pancreas	Healthy	GPR137C,ZNF335,TCEAL5, etc.	2.33e-02
KDM5B	INCAF	Pancreas	Healthy	GPR137C,ZNF335,TCEAL5, etc.	1.70e-02
KDM5B	MSC	Pancreas	PanIN	GPR137C,ZNF335,TCEAL5, etc.	3.96e-02

∗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

KDM5B

SNV

Missense_Mutation

rs777450660

c.378N>C

p.Lys126Asn

p.K126N

Q9UGL1

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

KDM5B

SNV

Missense_Mutation

c.365A>G

p.His122Arg

p.H122R

Q9UGL1

protein_coding

deleterious(0.05)

possibly_damaging(0.783)

TCGA-A1-A0SF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

KDM5B

SNV

Missense_Mutation

c.3241N>G

p.Arg1081Gly

p.R1081G

Q9UGL1

protein_coding

tolerated(0.07)

benign(0.081)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

KDM5B

SNV

Missense_Mutation

c.2530N>C

p.Glu844Gln

p.E844Q

Q9UGL1

protein_coding

deleterious(0.03)

possibly_damaging(0.698)

TCGA-A2-A0YH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

KDM5B

SNV

Missense_Mutation

c.1762N>G

p.Leu588Val

p.L588V

Q9UGL1

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

KDM5B

SNV

Missense_Mutation

c.257G>A

p.Arg86His

p.R86H

Q9UGL1

protein_coding

deleterious(0.01)

probably_damaging(0.987)

TCGA-A8-A08S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

KDM5B

SNV

Missense_Mutation

rs760532266

c.2134N>A

p.Asp712Asn

p.D712N

Q9UGL1

protein_coding

tolerated(0.18)

benign(0.311)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

KDM5B

SNV

Missense_Mutation

rs757818490

c.1817G>A

p.Arg606Gln

p.R606Q

Q9UGL1

protein_coding

deleterious(0)

possibly_damaging(0.754)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KDM5B

SNV

Missense_Mutation

rs370972925

c.881N>A

p.Arg294His

p.R294H

Q9UGL1

protein_coding

deleterious(0.01)

probably_damaging(0.972)

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

KDM5B

SNV

Missense_Mutation

novel

c.1596N>G

p.Phe532Leu

p.F532L

Q9UGL1

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

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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
10765	KDM5B	ENZYME	inhibitor	375973270
10765	KDM5B	ENZYME	inhibitor	310264759
10765	KDM5B	ENZYME	inhibitor	178103605
10765	KDM5B	ENZYME	inhibitor	381118851
10765	KDM5B	ENZYME	inhibitor	178103606

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