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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Center for Computational Systems Medicine
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Gene summary

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Malignant transformation analysis

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Malignant transformation related pathway analysis

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Cell-cell communication analysis

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Single-cell gene regulatory network inference analysis

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Somatic mutation of malignant transformation related genes

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Related drugs of malignant transformation related genes

Gene: ATF4

Gene summary for ATF4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

ATF4

Gene ID

468

Gene nameactivating transcription factor 4
Gene AliasCREB-2
Cytomap22q13.1
Gene Typeprotein-coding
GO ID

GO:0000122

UniProtAcc

P18848


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Malignant transformation analysis

check button 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
check button Malignant transformation involving gene list.
Entrez IDSymbolReplicatesSpeciesOrganTissueAdj P-valueLog2FCMalignancy
468ATF4GSM4909277HumanBreastPrecancer4.75e-028.18e-020.0177
468ATF4GSM4909280HumanBreastPrecancer6.69e-053.40e-010.0305
468ATF4GSM4909286HumanBreastIDC2.22e-04-1.43e-010.1081
468ATF4GSM4909287HumanBreastIDC4.27e-12-4.06e-010.2057
468ATF4GSM4909288HumanBreastIDC3.21e-05-3.96e-010.0988
468ATF4GSM4909290HumanBreastIDC2.19e-03-2.60e-010.2096
468ATF4GSM4909292HumanBreastIDC4.62e-022.65e-010.1236
468ATF4GSM4909293HumanBreastIDC3.10e-19-4.46e-010.1581
468ATF4GSM4909294HumanBreastIDC1.26e-17-5.33e-010.2022
468ATF4GSM4909296HumanBreastIDC6.18e-14-3.87e-010.1524
468ATF4GSM4909297HumanBreastIDC1.72e-22-3.00e-010.1517
468ATF4GSM4909298HumanBreastIDC1.68e-10-3.08e-010.1551
468ATF4GSM4909301HumanBreastIDC1.36e-24-6.88e-010.1577
468ATF4GSM4909302HumanBreastIDC7.67e-27-6.33e-010.1545
468ATF4GSM4909304HumanBreastIDC1.61e-03-3.33e-010.1636
468ATF4GSM4909305HumanBreastIDC2.10e-03-2.43e-010.0436
468ATF4GSM4909306HumanBreastIDC1.95e-12-4.24e-010.1564
468ATF4GSM4909307HumanBreastIDC7.96e-17-5.59e-010.1569
468ATF4GSM4909308HumanBreastIDC7.96e-26-6.05e-010.158
468ATF4GSM4909309HumanBreastIDC4.51e-07-2.47e-010.0483
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
BreastThe image shows the transcriptomic changes along malignancy continuum.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.IDC: Invasive ductal carcinoma
DCIS: Ductal carcinoma in situ
Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Colorectum (GSE201348)The image shows the transcriptomic changes along malignancy continuum.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.FAP: Familial adenomatous polyposis
CRC: Colorectal cancer
Colorectum (HTA11)The image shows the transcriptomic changes along malignancy continuum.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.AD: Adenomas
SER: Sessile serrated lesions
MSI-H: Microsatellite-high colorectal cancer
MSS: Microsatellite stable colorectal cancer
EndometriumThe image shows the transcriptomic changes along malignancy continuum.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.AEH: Atypical endometrial hyperplasia
EEC: Endometrioid Cancer
EsophagusThe image shows the transcriptomic changes along malignancy continuum.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.ESCC: Esophageal squamous cell carcinoma
HGIN: High-grade intraepithelial neoplasias
LGIN: Low-grade intraepithelial neoplasias
LiverThe image shows the transcriptomic changes along malignancy continuum.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.HCC: Hepatocellular carcinoma
NAFLD: Non-alcoholic fatty liver disease
Oral CavityThe image shows the transcriptomic changes along malignancy continuum.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.EOLP: Erosive Oral lichen planus
LP: leukoplakia
NEOLP: Non-erosive oral lichen planus
OSCC: Oral squamous cell carcinoma
ProstateThe image shows the transcriptomic changes along malignancy continuum.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.BPH: Benign Prostatic Hyperplasia
SkinThe image shows the transcriptomic changes along malignancy continuum.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.AK: Actinic keratosis
cSCC: Cutaneous squamous cell carcinoma
SCCIS:squamous cell carcinoma in situ
ThyroidThe image shows the transcriptomic changes along malignancy continuum.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.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

check buttonFind out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer
check button Figure of enriched GO biological processes.
TissueDisease StageEnriched GO biological Processes
ColorectumADGO analysis - Figure of enriched GO biological processes: 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).
ColorectumSERGO analysis - Figure of enriched GO biological processes: 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).
ColorectumMSSGO analysis - Figure of enriched GO biological processes: 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).
ColorectumMSI-HGO analysis - Figure of enriched GO biological processes: 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).
ColorectumFAPGO analysis - Figure of enriched GO biological processes: 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).
∗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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check button Enriched GO biological processes.
GO IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustCount
GO:007099716EndometriumAEHneuron death56/2100361/187237.51e-034.26e-0256
GO:19015222EndometriumAEHpositive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus7/210022/187238.22e-034.51e-027
GO:01101481EndometriumAEHbiomineralization30/2100171/187238.63e-034.71e-0230
GO:00466856EndometriumAEHresponse to arsenic-containing substance9/210033/187238.71e-034.75e-029
GO:009719317EndometriumEECintrinsic apoptotic signaling pathway80/2168288/187233.35e-149.13e-1280
GO:000641315EndometriumEECtranslational initiation42/2168118/187237.65e-121.24e-0942
GO:000697917EndometriumEECresponse to oxidative stress99/2168446/187239.02e-111.13e-0899
GO:006219717EndometriumEECcellular response to chemical stress77/2168337/187232.87e-092.10e-0777
GO:003497617EndometriumEECresponse to endoplasmic reticulum stress63/2168256/187233.84e-092.71e-0763
GO:000641717EndometriumEECregulation of translation94/2168468/187235.37e-082.88e-0694
GO:004851114EndometriumEECrhythmic process67/2168298/187235.86e-083.11e-0667
GO:003459917EndometriumEECcellular response to oxidative stress63/2168288/187234.05e-071.58e-0563
GO:003596617EndometriumEECresponse to topologically incorrect protein41/2168159/187235.20e-072.00e-0541
GO:000164914EndometriumEECosteoblast differentiation53/2168229/187235.32e-072.02e-0553
GO:000698617EndometriumEECresponse to unfolded protein37/2168137/187235.40e-072.04e-0537
GO:000644614EndometriumEECregulation of translational initiation25/216879/187231.62e-065.03e-0525
GO:000150313EndometriumEECossification79/2168408/187232.72e-067.67e-0579
GO:190121617EndometriumEECpositive regulation of neuron death28/216897/187233.08e-068.48e-0528
GO:003292212EndometriumEECcircadian regulation of gene expression22/216868/187234.49e-061.14e-0422
GO:000762314EndometriumEECcircadian rhythm46/2168210/187231.37e-052.73e-0446
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0501224BreastIDCParkinson disease107/867266/84652.57e-398.36e-376.26e-37107
hsa0502023BreastIDCPrion disease102/867273/84653.70e-344.01e-323.00e-32102
hsa0501023BreastIDCAlzheimer disease107/867384/84651.70e-237.88e-225.90e-22107
hsa0501423BreastIDCAmyotrophic lateral sclerosis102/867364/84651.29e-225.22e-213.91e-21102
hsa0502223BreastIDCPathways of neurodegeneration - multiple diseases116/867476/84653.63e-201.18e-188.82e-19116
hsa0493223BreastIDCNon-alcoholic fatty liver disease50/867155/84653.48e-148.08e-136.05e-1350
hsa0491523BreastIDCEstrogen signaling pathway35/867138/84652.55e-075.18e-063.88e-0635
hsa0421022BreastIDCApoptosis31/867136/84651.34e-051.61e-041.20e-0431
hsa0414124BreastIDCProtein processing in endoplasmic reticulum36/867174/84652.73e-052.86e-042.14e-0436
hsa050312BreastIDCAmphetamine addiction18/86769/84651.42e-041.36e-031.01e-0318
hsa0516624BreastIDCHuman T-cell leukemia virus 1 infection40/867222/84652.52e-042.21e-031.66e-0340
hsa0516324BreastIDCHuman cytomegalovirus infection39/867225/84656.66e-045.41e-034.05e-0339
hsa0413723BreastIDCMitophagy - animal17/86772/84657.61e-046.04e-034.52e-0317
hsa0520322BreastIDCViral carcinogenesis34/867204/84652.82e-031.86e-021.39e-0234
hsa0541724BreastIDCLipid and atherosclerosis35/867215/84653.67e-032.29e-021.71e-0235
hsa0501234BreastIDCParkinson disease107/867266/84652.57e-398.36e-376.26e-37107
hsa0502033BreastIDCPrion disease102/867273/84653.70e-344.01e-323.00e-32102
hsa0501033BreastIDCAlzheimer disease107/867384/84651.70e-237.88e-225.90e-22107
hsa0501433BreastIDCAmyotrophic lateral sclerosis102/867364/84651.29e-225.22e-213.91e-21102
hsa0502233BreastIDCPathways of neurodegeneration - multiple diseases116/867476/84653.63e-201.18e-188.82e-19116
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Cell-cell communication analysis

check buttonIdentification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states
LigandReceptorLRpairPathwayTissueDisease Stage
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Single-cell gene regulatory network inference analysis

check buttonFind out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states
TFCell TypeTissueDisease StageTarget GeneRSSRegulon Activity
ATF4PLAColorectumADRNF157,HERPUD1,EIF1, etc.5.18e-01The 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.
ATF4PLAColorectumADJRNF157,HERPUD1,EIF1, etc.2.95e-01The 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.
ATF4PLAColorectumCRCRNF157,HERPUD1,EIF1, etc.2.78e-01The 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.
ATF4PLAColorectumFAPRNF157,HERPUD1,EIF1, etc.2.93e-01The 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.
ATF4PLAColorectumHealthyRNF157,HERPUD1,EIF1, etc.3.81e-01The 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.
ATF4PLAColorectumMSI-HRNF157,HERPUD1,EIF1, etc.3.02e-01The 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.
ATF4PLAColorectumMSSRNF157,HERPUD1,EIF1, etc.2.09e-01The 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.
ATF4PLAColorectumSERRNF157,HERPUD1,EIF1, etc.5.22e-01The 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.
ATF4CD8TEFFEndometriumEECHPRT1,EIF1,ENPP4, etc.1.50e-01The 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.
ATF4PLALiverHealthyCD9,EIF1,CD36, etc.5.61e-01The 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.
∗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

check buttonAnnotation of somatic variants for genes involved in malignant transformation
Hugo SymbolVariant ClassVariant ClassificationdbSNP RSHGVScHGVSpHGVSp ShortSWISSPROTBIOTYPESIFTPolyPhenTumor Sample BarcodeTissueHistologySexAgeStageTherapy TypesDrugsOutcome
ATF4SNVMissense_Mutationc.60C>Gp.Phe20Leup.F20LP18848protein_codingtolerated(0.15)benign(0.294)TCGA-A2-A04P-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapytaxolPD
ATF4SNVMissense_Mutationnovelc.697N>Gp.Gln233Glup.Q233EP18848protein_codingtolerated(0.14)possibly_damaging(0.528)TCGA-AC-A3W6-01Breastbreast invasive carcinomaFemale>=65III/IVUnknownUnknownSD
ATF4SNVMissense_Mutationc.790N>Gp.Pro264Alap.P264AP18848protein_codingdeleterious(0.04)benign(0.251)TCGA-D8-A27G-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
ATF4insertionFrame_Shift_Insnovelc.846_847insAp.Met285AsnfsTer10p.M285Nfs*10P18848protein_codingTCGA-OL-A5D7-01Breastbreast invasive carcinomaFemale>=65I/IIChemotherapycytoxanCR
ATF4SNVMissense_Mutationrs547982920c.685N>Gp.Leu229Valp.L229VP18848protein_codingtolerated(0.34)benign(0.003)TCGA-C5-A1MK-01Cervixcervical & endocervical cancerFemale>=65III/IVChemotherapycarboplatinPD
ATF4SNVMissense_Mutationnovelc.922N>Tp.Gly308Cysp.G308CP18848protein_codingdeleterious(0)probably_damaging(0.996)TCGA-DS-A1OB-01Cervixcervical & endocervical cancerFemale<65I/IIChemotherapycarboplatinPD
ATF4SNVMissense_Mutationc.430N>Gp.Leu144Valp.L144VP18848protein_codingtolerated(0.19)benign(0.275)TCGA-EK-A2R8-01Cervixcervical & endocervical cancerFemale<65I/IIUnknownUnknownSD
ATF4SNVMissense_Mutationc.305N>Cp.Ile102Thrp.I102TP18848protein_codingtolerated(0.47)benign(0)TCGA-AA-3663-01Colorectumcolon adenocarcinomaMale<65I/IIUnknownUnknownSD
ATF4SNVMissense_Mutationc.335N>Gp.Leu112Argp.L112RP18848protein_codingdeleterious(0)probably_damaging(0.929)TCGA-AA-3811-01Colorectumcolon adenocarcinomaFemale>=65III/IVUnknownUnknownPD
ATF4SNVMissense_Mutationnovelc.617N>Gp.Gln206Argp.Q206RP18848protein_codingtolerated(0.24)benign(0.015)TCGA-CA-6717-01Colorectumcolon adenocarcinomaMale<65I/IIChemotherapyoxaliplatinCR
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Related drugs of malignant transformation related genes

check buttonIdentification of chemicals and drugs interact with genes involved in malignant transfromation
(DGIdb 4.0)
Entrez IDSymbolCategoryInteraction TypesDrug Claim NameDrug NamePMIDs
468ATF4TRANSPORTER, TRANSCRIPTION FACTORVITAMIN E11043924
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