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: CROCC

Gene summary for CROCC

Gene summary.

Gene information	Species	Human
	Gene symbol	CROCC
	Gene ID	9696
	Gene name	ciliary rootlet coiled-coil, rootletin
	Gene Alias	ROLT
	Cytomap	1p36.13
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q5TZA2

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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
9696	CROCC	CCI_1	Human	Cervix	CC	3.23e-02	3.22e-01	0.528
9696	CROCC	CCI_2	Human	Cervix	CC	1.56e-07	5.94e-01	0.5249
9696	CROCC	CCI_3	Human	Cervix	CC	2.00e-07	5.34e-01	0.516
9696	CROCC	CCII_1	Human	Cervix	CC	2.70e-02	2.52e-01	0.3249
9696	CROCC	A015-C-203	Human	Colorectum	FAP	2.47e-02	-1.31e-02	-0.1294
9696	CROCC	A015-C-104	Human	Colorectum	FAP	1.00e-03	7.24e-02	-0.1899
9696	CROCC	A002-C-016	Human	Colorectum	FAP	4.67e-02	-7.31e-02	0.0521
9696	CROCC	A002-C-116	Human	Colorectum	FAP	1.71e-03	-3.55e-02	-0.0452
9696	CROCC	LZE2T	Human	Esophagus	ESCC	7.43e-04	7.48e-01	0.082
9696	CROCC	LZE7T	Human	Esophagus	ESCC	2.07e-05	5.06e-01	0.0667
9696	CROCC	LZE22D1	Human	Esophagus	HGIN	1.40e-04	2.26e-01	0.0595
9696	CROCC	P1T-E	Human	Esophagus	ESCC	1.32e-10	6.26e-01	0.0875
9696	CROCC	P2T-E	Human	Esophagus	ESCC	1.19e-09	1.08e-01	0.1177
9696	CROCC	P4T-E	Human	Esophagus	ESCC	3.90e-09	2.24e-01	0.1323
9696	CROCC	P8T-E	Human	Esophagus	ESCC	1.98e-04	8.98e-02	0.0889
9696	CROCC	P9T-E	Human	Esophagus	ESCC	1.54e-11	2.42e-01	0.1131
9696	CROCC	P10T-E	Human	Esophagus	ESCC	8.68e-17	1.71e-01	0.116
9696	CROCC	P11T-E	Human	Esophagus	ESCC	7.78e-06	3.46e-01	0.1426
9696	CROCC	P12T-E	Human	Esophagus	ESCC	1.86e-11	2.90e-01	0.1122
9696	CROCC	P15T-E	Human	Esophagus	ESCC	6.56e-13	2.75e-01	0.1149

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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:190382910	Cervix	CC	positive regulation of cellular protein localization	72/2311	276/18723	3.20e-10	4.46e-08	72
GO:00313467	Cervix	CC	positive regulation of cell projection organization	72/2311	353/18723	1.04e-05	2.32e-04	72
GO:00018949	Cervix	CC	tissue homeostasis	57/2311	268/18723	2.43e-05	4.21e-04	57
GO:00516567	Cervix	CC	establishment of organelle localization	76/2311	390/18723	3.17e-05	5.21e-04	76
GO:00602498	Cervix	CC	anatomical structure homeostasis	63/2311	314/18723	6.03e-05	8.68e-04	63
GO:19021153	Cervix	CC	regulation of organelle assembly	40/2311	186/18723	2.92e-04	3.15e-03	40
GO:19021171	Cervix	CC	positive regulation of organelle assembly	19/2311	67/18723	3.42e-04	3.58e-03	19
GO:01200328	Cervix	CC	regulation of plasma membrane bounded cell projection assembly	38/2311	186/18723	1.14e-03	9.35e-03	38
GO:00604917	Cervix	CC	regulation of cell projection assembly	38/2311	188/18723	1.40e-03	1.10e-02	38
GO:00018957	Cervix	CC	retina homeostasis	19/2311	79/18723	2.94e-03	1.94e-02	19
GO:19038294	Colorectum	FAP	positive regulation of cellular protein localization	79/2622	276/18723	1.59e-10	4.38e-08	79
GO:00516563	Colorectum	FAP	establishment of organelle localization	97/2622	390/18723	5.91e-09	9.48e-07	97
GO:00313463	Colorectum	FAP	positive regulation of cell projection organization	82/2622	353/18723	1.78e-06	7.35e-05	82
GO:00018944	Colorectum	FAP	tissue homeostasis	61/2622	268/18723	6.71e-05	1.28e-03	61
GO:00602494	Colorectum	FAP	anatomical structure homeostasis	69/2622	314/18723	7.51e-05	1.37e-03	69
GO:01200323	Colorectum	FAP	regulation of plasma membrane bounded cell projection assembly	39/2622	186/18723	5.84e-03	3.73e-02	39
GO:0010669	Colorectum	FAP	epithelial structure maintenance	10/2622	30/18723	5.90e-03	3.75e-02	10
GO:00604912	Colorectum	FAP	regulation of cell projection assembly	39/2622	188/18723	7.01e-03	4.29e-02	39
GO:190382926	Esophagus	HGIN	positive regulation of cellular protein localization	75/2587	276/18723	3.19e-09	2.30e-07	75
GO:005165616	Esophagus	HGIN	establishment of organelle localization	90/2587	390/18723	4.27e-07	1.94e-05	90

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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

CROCC

SNV

Missense_Mutation

rs764904297

c.1060N>A

p.Glu354Lys

p.E354K

Q5TZA2

protein_coding

tolerated(0.7)

benign(0.09)

TCGA-A2-A4RX-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CROCC

SNV

Missense_Mutation

c.3904G>A

p.Glu1302Lys

p.E1302K

Q5TZA2

protein_coding

deleterious(0.01)

possibly_damaging(0.655)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CROCC

SNV

Missense_Mutation

novel

c.1789N>A

p.Ala597Thr

p.A597T

Q5TZA2

protein_coding

tolerated(0.35)

benign(0.003)

TCGA-AC-A8OP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CROCC

SNV

Missense_Mutation

c.3290G>C

p.Arg1097Pro

p.R1097P

Q5TZA2

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-AO-A12H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CROCC

SNV

Missense_Mutation

rs745666217

c.2320N>T

p.Arg774Trp

p.R774W

Q5TZA2

protein_coding

deleterious(0)

possibly_damaging(0.799)

TCGA-AR-A24M-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

CROCC

SNV

Missense_Mutation

c.3290G>C

p.Arg1097Pro

p.R1097P

Q5TZA2

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-B6-A1KC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CROCC

SNV

Missense_Mutation

novel

c.3778N>A

p.Glu1260Lys

p.E1260K

Q5TZA2

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CROCC

SNV

Missense_Mutation

c.2371G>C

p.Glu791Gln

p.E791Q

Q5TZA2

protein_coding

deleterious(0.02)

benign(0.097)

TCGA-BH-A0DX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CROCC

SNV

Missense_Mutation

c.4649N>A

p.Thr1550Asn

p.T1550N

Q5TZA2

protein_coding

tolerated(0.72)

benign(0.037)

TCGA-BH-A0DZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

CROCC

SNV

Missense_Mutation

c.3290N>C

p.Arg1097Pro

p.R1097P

Q5TZA2

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-BH-A0E9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

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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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