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: MAP4K4

Gene summary for MAP4K4

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

MAP4K4

Gene ID

9448

Gene namemitogen-activated protein kinase kinase kinase kinase 4
Gene AliasFLH21957
Cytomap2q11.2
Gene Typeprotein-coding
GO ID

GO:0000165

UniProtAcc

O95819


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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
9448MAP4K4LZE2THumanEsophagusESCC5.45e-089.26e-010.082
9448MAP4K4LZE4THumanEsophagusESCC1.90e-141.01e-010.0811
9448MAP4K4LZE7THumanEsophagusESCC6.00e-095.96e-010.0667
9448MAP4K4LZE22THumanEsophagusESCC2.98e-033.74e-010.068
9448MAP4K4LZE24THumanEsophagusESCC1.31e-121.70e-010.0596
9448MAP4K4LZE6THumanEsophagusESCC2.12e-031.10e-010.0845
9448MAP4K4P2T-EHumanEsophagusESCC1.75e-142.93e-010.1177
9448MAP4K4P4T-EHumanEsophagusESCC1.09e-184.98e-010.1323
9448MAP4K4P5T-EHumanEsophagusESCC1.79e-202.41e-010.1327
9448MAP4K4P8T-EHumanEsophagusESCC3.31e-232.34e-010.0889
9448MAP4K4P9T-EHumanEsophagusESCC2.70e-175.34e-010.1131
9448MAP4K4P10T-EHumanEsophagusESCC5.54e-417.78e-010.116
9448MAP4K4P11T-EHumanEsophagusESCC4.03e-114.21e-010.1426
9448MAP4K4P12T-EHumanEsophagusESCC1.64e-143.33e-010.1122
9448MAP4K4P15T-EHumanEsophagusESCC6.75e-145.09e-010.1149
9448MAP4K4P16T-EHumanEsophagusESCC2.64e-152.47e-010.1153
9448MAP4K4P17T-EHumanEsophagusESCC9.37e-092.46e-010.1278
9448MAP4K4P19T-EHumanEsophagusESCC3.83e-067.37e-010.1662
9448MAP4K4P21T-EHumanEsophagusESCC1.17e-336.90e-010.1617
9448MAP4K4P22T-EHumanEsophagusESCC8.00e-283.64e-010.1236
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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
LungThe 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.AAH: Atypical adenomatous hyperplasia
AIS: Adenocarcinoma in situ
IAC: Invasive lung adenocarcinoma
MIA: Minimally invasive adenocarcinoma
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:000167817Oral cavityEOLPcellular glucose homeostasis36/2218172/187234.51e-043.98e-0336
GO:00510517Oral cavityEOLPnegative regulation of transport80/2218470/187235.11e-044.44e-0380
GO:0034284110Oral cavityEOLPresponse to monosaccharide44/2218225/187235.38e-044.63e-0344
GO:0009746110Oral cavityEOLPresponse to hexose43/2218219/187235.67e-044.81e-0343
GO:007030224Oral cavityEOLPregulation of stress-activated protein kinase signaling cascade39/2218195/187236.89e-045.70e-0339
GO:00518947Oral cavityEOLPpositive regulation of focal adhesion assembly10/221828/187239.28e-047.08e-0310
GO:00435479Oral cavityEOLPpositive regulation of GTPase activity47/2218255/187231.34e-039.33e-0347
GO:007133317Oral cavityEOLPcellular response to glucose stimulus31/2218151/187231.50e-031.01e-0231
GO:19018889Oral cavityEOLPregulation of cell junction assembly39/2218204/187231.67e-031.11e-0239
GO:003287224Oral cavityEOLPregulation of stress-activated MAPK cascade37/2218192/187231.87e-031.21e-0237
GO:007133117Oral cavityEOLPcellular response to hexose stimulus31/2218153/187231.87e-031.21e-0231
GO:000974918Oral cavityEOLPresponse to glucose40/2218212/187231.89e-031.21e-0240
GO:007132617Oral cavityEOLPcellular response to monosaccharide stimulus31/2218154/187232.08e-031.32e-0231
GO:007132218Oral cavityEOLPcellular response to carbohydrate stimulus32/2218163/187232.70e-031.62e-0232
GO:004259317Oral cavityEOLPglucose homeostasis46/2218258/187232.96e-031.74e-0246
GO:003350017Oral cavityEOLPcarbohydrate homeostasis46/2218259/187233.20e-031.86e-0246
GO:004632814Oral cavityEOLPregulation of JNK cascade27/2218133/187233.44e-031.98e-0227
GO:00311021Oral cavityEOLPneuron projection regeneration15/221860/187233.58e-032.03e-0215
GO:00705701Oral cavityEOLPregulation of neuron projection regeneration10/221833/187233.76e-032.10e-0210
GO:01501177Oral cavityEOLPpositive regulation of cell-substrate junction organization10/221833/187233.76e-032.10e-0210
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa040108LungIACMAPK signaling pathway62/1053302/84653.54e-056.38e-044.24e-0462
hsa0401011LungIACMAPK signaling pathway62/1053302/84653.54e-056.38e-044.24e-0462
hsa0401021LungAISMAPK signaling pathway57/961302/84656.41e-059.43e-046.03e-0457
hsa0401031LungAISMAPK signaling pathway57/961302/84656.41e-059.43e-046.03e-0457
hsa0401014Oral cavityOSCCMAPK signaling pathway165/3704302/84657.11e-052.74e-041.40e-04165
hsa0401015Oral cavityOSCCMAPK signaling pathway165/3704302/84657.11e-052.74e-041.40e-04165
hsa0401023Oral cavityEOLPMAPK signaling pathway68/1218302/84657.48e-053.40e-042.01e-0468
hsa0401033Oral cavityEOLPMAPK signaling pathway68/1218302/84657.48e-053.40e-042.01e-0468
hsa0401041Oral cavityNEOLPMAPK signaling pathway59/1112302/84659.40e-044.67e-032.94e-0359
hsa0401051Oral cavityNEOLPMAPK signaling pathway59/1112302/84659.40e-044.67e-032.94e-0359
hsa0401010ProstateBPHMAPK signaling pathway87/1718302/84652.05e-041.13e-036.98e-0487
hsa0401013ProstateBPHMAPK signaling pathway87/1718302/84652.05e-041.13e-036.98e-0487
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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
MAP4K4SNVMissense_Mutationc.3526N>Tp.Val1176Phep.V1176Fprotein_codingdeleterious_low_confidence(0.01)probably_damaging(0.98)TCGA-A8-A09X-01Breastbreast invasive carcinomaFemale<65III/IVUnknownUnknownSD
MAP4K4SNVMissense_Mutationc.3715N>Cp.Phe1239Leup.F1239Lprotein_codingdeleterious_low_confidence(0)probably_damaging(0.931)TCGA-AC-A23H-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownPD
MAP4K4SNVMissense_Mutationc.451N>Tp.His151Tyrp.H151Yprotein_codingdeleterious_low_confidence(0)probably_damaging(0.957)TCGA-AC-A2FG-01Breastbreast invasive carcinomaFemale>=65I/IIHormone TherapyarimidexCR
MAP4K4SNVMissense_Mutationnovelc.643N>Ap.Asp215Asnp.D215Nprotein_codingdeleterious_low_confidence(0)probably_damaging(0.994)TCGA-BH-A0B6-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
MAP4K4SNVMissense_Mutationc.1246G>Cp.Glu416Glnp.E416Qprotein_codingtolerated_low_confidence(0.09)possibly_damaging(0.888)TCGA-D8-A27G-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
MAP4K4SNVMissense_Mutationc.592N>Ap.Glu198Lysp.E198Kprotein_codingdeleterious_low_confidence(0)probably_damaging(0.991)TCGA-E2-A1LG-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapydoxorubicinSD
MAP4K4SNVMissense_Mutationc.673N>Cp.Glu225Glnp.E225Qprotein_codingdeleterious_low_confidence(0.02)probably_damaging(0.991)TCGA-E2-A1LG-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapydoxorubicinSD
MAP4K4SNVMissense_Mutationc.2322N>Cp.Leu774Phep.L774Fprotein_codingtolerated_low_confidence(0.59)probably_damaging(0.991)TCGA-GM-A2DI-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapytaxotereCR
MAP4K4SNVMissense_Mutationnovelc.2741N>Cp.Gly914Alap.G914Aprotein_codingtolerated_low_confidence(0.39)probably_damaging(0.997)TCGA-OL-A5RW-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapyadriamycinCR
MAP4K4insertionNonsense_Mutationnovelc.1598_1599insGGAGGGTCAGACATAGACACAAGAGACGTAGATp.Asp533delinsGluGluGlyGlnThrTerThrGlnGluThrTerIlep.D533delinsEEGQT*TQET*Iprotein_codingTCGA-AO-A0J9-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapycyclophosphamidePD
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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
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMECYC-116CYC-116
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMESOTRASTAURINSOTRASTAURIN
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMEPAZOPANIBPAZOPANIB
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMEDNDI1417467CHEMBL1997335
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMEAST-487AST-487
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMEPD-0166285PD-0166285
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMESB-220025SB-220025
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMECEDIRANIBCEDIRANIB
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMEOSI-632OSI-632
9448MAP4K4DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYMEAZD-1152-HQPAAZD-1152-HQPA
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