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: GRPEL1

Gene summary for GRPEL1

Gene summary.

Gene information	Species	Human
	Gene symbol	GRPEL1
	Gene ID	80273
	Gene name	GrpE like 1, mitochondrial
	Gene Alias	GrpE
	Cytomap	4p16.1
	Gene Type	protein-coding
	GO ID	GO:0006457
	UniProtAcc	Q9HAV7

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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
80273	GRPEL1	LZE2T	Human	Esophagus	ESCC	6.30e-03	4.78e-01	0.082
80273	GRPEL1	LZE4T	Human	Esophagus	ESCC	8.40e-07	-7.02e-02	0.0811
80273	GRPEL1	LZE5T	Human	Esophagus	ESCC	1.86e-02	-5.23e-02	0.0514
80273	GRPEL1	LZE24T	Human	Esophagus	ESCC	5.97e-06	2.54e-01	0.0596
80273	GRPEL1	P2T-E	Human	Esophagus	ESCC	6.88e-19	4.99e-01	0.1177
80273	GRPEL1	P4T-E	Human	Esophagus	ESCC	1.06e-11	6.04e-01	0.1323
80273	GRPEL1	P5T-E	Human	Esophagus	ESCC	3.59e-21	6.10e-01	0.1327
80273	GRPEL1	P8T-E	Human	Esophagus	ESCC	1.42e-16	2.59e-01	0.0889
80273	GRPEL1	P9T-E	Human	Esophagus	ESCC	3.27e-06	2.97e-01	0.1131
80273	GRPEL1	P10T-E	Human	Esophagus	ESCC	2.06e-23	6.91e-02	0.116
80273	GRPEL1	P11T-E	Human	Esophagus	ESCC	3.77e-07	8.58e-01	0.1426
80273	GRPEL1	P12T-E	Human	Esophagus	ESCC	2.12e-20	3.86e-01	0.1122
80273	GRPEL1	P15T-E	Human	Esophagus	ESCC	5.14e-05	1.72e-01	0.1149
80273	GRPEL1	P16T-E	Human	Esophagus	ESCC	2.15e-14	4.23e-01	0.1153
80273	GRPEL1	P17T-E	Human	Esophagus	ESCC	1.07e-08	6.66e-01	0.1278
80273	GRPEL1	P20T-E	Human	Esophagus	ESCC	1.83e-11	2.74e-01	0.1124
80273	GRPEL1	P21T-E	Human	Esophagus	ESCC	2.84e-16	4.48e-01	0.1617
80273	GRPEL1	P22T-E	Human	Esophagus	ESCC	4.10e-11	1.90e-01	0.1236
80273	GRPEL1	P23T-E	Human	Esophagus	ESCC	1.34e-19	7.49e-01	0.108
80273	GRPEL1	P24T-E	Human	Esophagus	ESCC	3.21e-12	3.21e-01	0.1287

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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
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:0072594110	Esophagus	ESCC	establishment of protein localization to organelle	311/8552	422/18723	3.02e-32	2.13e-29	311
GO:0006605111	Esophagus	ESCC	protein targeting	229/8552	314/18723	4.93e-23	1.01e-20	229
GO:0006457110	Esophagus	ESCC	protein folding	163/8552	212/18723	1.13e-20	1.74e-18	163
GO:0006839110	Esophagus	ESCC	mitochondrial transport	187/8552	254/18723	8.35e-20	9.81e-18	187
GO:0072655110	Esophagus	ESCC	establishment of protein localization to mitochondrion	97/8552	120/18723	2.17e-15	1.33e-13	97
GO:0070585110	Esophagus	ESCC	protein localization to mitochondrion	100/8552	125/18723	2.96e-15	1.77e-13	100
GO:001703818	Esophagus	ESCC	protein import	149/8552	206/18723	5.90e-15	3.31e-13	149
GO:0006626110	Esophagus	ESCC	protein targeting to mitochondrion	81/8552	100/18723	3.60e-13	1.67e-11	81
GO:00718069	Esophagus	ESCC	protein transmembrane transport	47/8552	59/18723	9.02e-08	1.51e-06	47
GO:1990542110	Esophagus	ESCC	mitochondrial transmembrane transport	72/8552	102/18723	2.94e-07	4.23e-06	72
GO:00650026	Esophagus	ESCC	intracellular protein transmembrane transport	40/8552	51/18723	1.76e-06	2.08e-05	40
GO:00447433	Esophagus	ESCC	protein transmembrane import into intracellular organelle	29/8552	36/18723	1.91e-05	1.67e-04	29
GO:00301503	Esophagus	ESCC	protein import into mitochondrial matrix	16/8552	20/18723	1.85e-03	8.40e-03	16
GO:00064577	Liver	Cirrhotic	protein folding	114/4634	212/18723	9.23e-20	2.31e-17	114
GO:007259412	Liver	Cirrhotic	establishment of protein localization to organelle	189/4634	422/18723	1.01e-19	2.45e-17	189
GO:00066057	Liver	Cirrhotic	protein targeting	148/4634	314/18723	3.86e-18	6.20e-16	148
GO:00068397	Liver	Cirrhotic	mitochondrial transport	112/4634	254/18723	1.03e-11	6.66e-10	112
GO:00705857	Liver	Cirrhotic	protein localization to mitochondrion	65/4634	125/18723	4.91e-11	2.77e-09	65
GO:00726557	Liver	Cirrhotic	establishment of protein localization to mitochondrion	63/4634	120/18723	5.70e-11	3.19e-09	63
GO:00066267	Liver	Cirrhotic	protein targeting to mitochondrion	53/4634	100/18723	1.19e-09	5.27e-08	53

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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

GRPEL1

SNV

Missense_Mutation

rs370293338

c.511N>A

p.Asp171Asn

p.D171N

Q9HAV7

protein_coding

tolerated(0.16)

benign(0.123)

TCGA-C8-A8HR-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

GRPEL1

insertion

In_Frame_Ins

novel

c.374_375insCCTCTCATGGAGATCCTTGCCGCTGAGGCAAGCATG

p.Val125_Pro126insLeuSerTrpArgSerLeuProLeuArgGlnAlaCys

p.V125_P126insLSWRSLPLRQAC

Q9HAV7

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

GRPEL1

insertion

Nonsense_Mutation

novel

c.226_227insTGCATATTTACAGTAGGAATTAAAGATTTGTTTAGCTACC

p.Glu76ValfsTer8

p.E76Vfs*8

Q9HAV7

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

GRPEL1

SNV

Missense_Mutation

rs766058514

c.610C>T

p.Arg204Cys

p.R204C

Q9HAV7

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-AA-3821-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

GRPEL1

SNV

Missense_Mutation

c.92C>T

p.Thr31Met

p.T31M

Q9HAV7

protein_coding

deleterious(0.02)

possibly_damaging(0.569)

TCGA-F4-6856-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Ancillary

leucovorin

GRPEL1

SNV

Missense_Mutation

c.580N>T

p.Val194Phe

p.V194F

Q9HAV7

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-G4-6588-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

GRPEL1

SNV

Missense_Mutation

novel

c.608G>A

p.Gly203Glu

p.G203E

Q9HAV7

protein_coding

tolerated(0.26)

benign(0.163)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

GRPEL1

SNV

Missense_Mutation

novel

c.328G>A

p.Asp110Asn

p.D110N

Q9HAV7

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

GRPEL1

SNV

Missense_Mutation

novel

c.608G>T

p.Gly203Val

p.G203V

Q9HAV7

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

GRPEL1

SNV

Missense_Mutation

c.132N>T

p.Met44Ile

p.M44I

Q9HAV7

protein_coding

tolerated(0.19)

benign(0)

TCGA-AP-A0LD-01

Endometrium

uterine corpus endometrioid carcinoma

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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