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: EIF2AK4

Gene summary for EIF2AK4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

EIF2AK4

Gene ID

440275

Gene nameeukaryotic translation initiation factor 2 alpha kinase 4
Gene AliasGCN2
Cytomap15q15.1
Gene Typeprotein-coding
GO ID

GO:0000075

UniProtAcc

Q9P2K8


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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
440275EIF2AK4LZE2THumanEsophagusESCC1.25e-038.29e-010.082
440275EIF2AK4LZE4THumanEsophagusESCC5.86e-115.37e-010.0811
440275EIF2AK4LZE20THumanEsophagusESCC2.15e-041.19e-010.0662
440275EIF2AK4LZE24THumanEsophagusESCC2.08e-144.77e-010.0596
440275EIF2AK4LZE21THumanEsophagusESCC2.87e-021.06e-010.0655
440275EIF2AK4P1T-EHumanEsophagusESCC1.21e-219.74e-010.0875
440275EIF2AK4P2T-EHumanEsophagusESCC3.00e-436.76e-010.1177
440275EIF2AK4P4T-EHumanEsophagusESCC7.45e-398.73e-010.1323
440275EIF2AK4P5T-EHumanEsophagusESCC2.23e-213.77e-010.1327
440275EIF2AK4P8T-EHumanEsophagusESCC3.63e-579.44e-010.0889
440275EIF2AK4P9T-EHumanEsophagusESCC1.25e-225.69e-010.1131
440275EIF2AK4P10T-EHumanEsophagusESCC1.09e-467.72e-010.116
440275EIF2AK4P11T-EHumanEsophagusESCC9.61e-136.16e-010.1426
440275EIF2AK4P12T-EHumanEsophagusESCC1.30e-468.93e-010.1122
440275EIF2AK4P15T-EHumanEsophagusESCC1.36e-124.26e-010.1149
440275EIF2AK4P16T-EHumanEsophagusESCC7.50e-345.73e-010.1153
440275EIF2AK4P17T-EHumanEsophagusESCC3.19e-156.14e-010.1278
440275EIF2AK4P19T-EHumanEsophagusESCC5.55e-064.98e-010.1662
440275EIF2AK4P20T-EHumanEsophagusESCC4.82e-307.13e-010.1124
440275EIF2AK4P21T-EHumanEsophagusESCC4.96e-396.73e-010.1617
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check button Transcriptomic changes along malignancy continuum.
TissueExpression DynamicsAbbreviation
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:0031667110Oral cavityLPresponse to nutrient levels165/4623474/187233.87e-071.12e-05165
GO:007121417Oral cavityLPcellular response to abiotic stimulus121/4623331/187238.45e-072.20e-05121
GO:010400417Oral cavityLPcellular response to environmental stimulus121/4623331/187238.45e-072.20e-05121
GO:000941112Oral cavityLPresponse to UV63/4623149/187231.74e-064.05e-0563
GO:000931417Oral cavityLPresponse to radiation155/4623456/187234.12e-068.49e-05155
GO:007147815Oral cavityLPcellular response to radiation73/4623186/187237.44e-061.41e-0473
GO:005160711Oral cavityLPdefense response to virus97/4623265/187239.31e-061.74e-0497
GO:014054611Oral cavityLPdefense response to symbiont97/4623265/187239.31e-061.74e-0497
GO:0031668110Oral cavityLPcellular response to extracellular stimulus91/4623246/187231.07e-051.94e-0491
GO:005109015Oral cavityLPregulation of DNA-binding transcription factor activity147/4623440/187232.00e-053.35e-04147
GO:014046712Oral cavityLPintegrated stress response signaling15/462322/187232.08e-053.44e-0415
GO:004355512Oral cavityLPregulation of translation in response to stress14/462320/187232.51e-054.04e-0414
GO:003464412Oral cavityLPcellular response to UV40/462390/187233.28e-055.02e-0440
GO:004355812Oral cavityLPregulation of translational initiation in response to stress11/462314/187233.49e-055.22e-0411
GO:003166919Oral cavityLPcellular response to nutrient levels79/4623215/187235.16e-057.21e-0479
GO:001604918Oral cavityLPcell growth155/4623482/187231.08e-041.31e-03155
GO:004578612Oral cavityLPnegative regulation of cell cycle127/4623385/187231.33e-041.53e-03127
GO:000926718Oral cavityLPcellular response to starvation59/4623156/187231.78e-041.99e-0359
GO:004478814Oral cavityLPmodulation by host of viral process17/462330/187231.81e-042.01e-0317
GO:005181713Oral cavityLPmodulation of process of other organism involved in symbiotic interaction35/462381/187231.97e-042.16e-0335
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa04141211EsophagusESCCProtein processing in endoplasmic reticulum147/4205174/84653.29e-221.10e-195.64e-20147
hsa0414010EsophagusESCCAutophagy - animal101/4205141/84657.60e-086.21e-073.18e-07101
hsa051609EsophagusESCCHepatitis C107/4205157/84651.75e-061.08e-055.55e-06107
hsa051629EsophagusESCCMeasles90/4205139/84652.16e-047.87e-044.03e-0490
hsa04141310EsophagusESCCProtein processing in endoplasmic reticulum147/4205174/84653.29e-221.10e-195.64e-20147
hsa0414015EsophagusESCCAutophagy - animal101/4205141/84657.60e-086.21e-073.18e-07101
hsa0516016EsophagusESCCHepatitis C107/4205157/84651.75e-061.08e-055.55e-06107
hsa0516213EsophagusESCCMeasles90/4205139/84652.16e-047.87e-044.03e-0490
hsa0414122LiverHCCProtein processing in endoplasmic reticulum146/4020174/84657.34e-242.46e-211.37e-21146
hsa0414021LiverHCCAutophagy - animal99/4020141/84653.08e-084.70e-072.61e-0799
hsa0516021LiverHCCHepatitis C94/4020157/84651.11e-034.10e-032.28e-0394
hsa0414132LiverHCCProtein processing in endoplasmic reticulum146/4020174/84657.34e-242.46e-211.37e-21146
hsa0414031LiverHCCAutophagy - animal99/4020141/84653.08e-084.70e-072.61e-0799
hsa0516031LiverHCCHepatitis C94/4020157/84651.11e-034.10e-032.28e-0394
hsa0414130Oral cavityOSCCProtein processing in endoplasmic reticulum143/3704174/84656.82e-262.28e-231.16e-23143
hsa051608Oral cavityOSCCHepatitis C103/3704157/84652.17e-081.96e-079.99e-08103
hsa041409Oral cavityOSCCAutophagy - animal94/3704141/84652.73e-082.38e-071.21e-0794
hsa051628Oral cavityOSCCMeasles90/3704139/84654.10e-072.50e-061.27e-0690
hsa04141113Oral cavityOSCCProtein processing in endoplasmic reticulum143/3704174/84656.82e-262.28e-231.16e-23143
hsa0516015Oral cavityOSCCHepatitis C103/3704157/84652.17e-081.96e-079.99e-08103
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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
∗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
EIF2AK4SNVMissense_Mutationnovelc.1790N>Tp.Gly597Valp.G597VQ9P2K8protein_codingdeleterious(0)probably_damaging(1)TCGA-A2-A4RX-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
EIF2AK4SNVMissense_Mutationnovelc.236N>Ap.Cys79Tyrp.C79YQ9P2K8protein_codingdeleterious(0)probably_damaging(1)TCGA-A7-A6VV-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycyclophosphamideCR
EIF2AK4SNVMissense_Mutationc.3685G>Ap.Asp1229Asnp.D1229NQ9P2K8protein_codingdeleterious(0.03)probably_damaging(0.999)TCGA-AC-A23H-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownPD
EIF2AK4SNVMissense_Mutationc.3796G>Ap.Asp1266Asnp.D1266NQ9P2K8protein_codingtolerated(0.96)benign(0.01)TCGA-AC-A23H-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownPD
EIF2AK4SNVMissense_Mutationc.1724N>Cp.Phe575Serp.F575SQ9P2K8protein_codingtolerated(0.2)benign(0.003)TCGA-AO-A1KR-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycyclophosphamideSD
EIF2AK4SNVMissense_Mutationrs763402151c.1378N>Cp.Glu460Glnp.E460QQ9P2K8protein_codingtolerated(0.09)probably_damaging(0.999)TCGA-BH-A0B6-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
EIF2AK4SNVMissense_Mutationc.4701N>Cp.Gln1567Hisp.Q1567HQ9P2K8protein_codingtolerated(0.76)benign(0.007)TCGA-BH-A0H5-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapycytoxanCR
EIF2AK4SNVMissense_Mutationrs752767858c.2345N>Cp.Gly782Alap.G782AQ9P2K8protein_codingtolerated(0.67)benign(0.019)TCGA-C8-A12X-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
EIF2AK4SNVMissense_Mutationnovelc.301G>Ap.Glu101Lysp.E101KQ9P2K8protein_codingdeleterious(0.01)possibly_damaging(0.808)TCGA-C8-A26Y-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
EIF2AK4SNVMissense_Mutationc.3791A>Cp.Lys1264Thrp.K1264TQ9P2K8protein_codingdeleterious(0.01)probably_damaging(1)TCGA-D8-A1JL-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
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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
440275EIF2AK4KINASE, ENZYME, SERINE THREONINE KINASE, DRUGGABLE GENOMEolanzapineOLANZAPINE24751813
440275EIF2AK4KINASE, ENZYME, SERINE THREONINE KINASE, DRUGGABLE GENOMErisperidoneRISPERIDONE24751813
440275EIF2AK4KINASE, ENZYME, SERINE THREONINE KINASE, DRUGGABLE GENOMEinhibitor249565849
440275EIF2AK4KINASE, ENZYME, SERINE THREONINE KINASE, DRUGGABLE GENOMEquetiapineQUETIAPINE24751813
440275EIF2AK4KINASE, ENZYME, SERINE THREONINE KINASE, DRUGGABLE GENOMEinhibitorHESPERADINHESPERADIN19035792
440275EIF2AK4KINASE, ENZYME, SERINE THREONINE KINASE, DRUGGABLE GENOMEhaloperidolHALOPERIDOL27023437,24751813
440275EIF2AK4KINASE, ENZYME, SERINE THREONINE KINASE, DRUGGABLE GENOMEziprasidoneZIPRASIDONE24751813
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