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: ARAF

Gene summary for ARAF

check button Gene summary.

Gene informationSpeciesHuman
Gene symbol

ARAF

Gene ID

369

Gene nameA-Raf proto-oncogene, serine/threonine kinase
Gene AliasA-RAF
CytomapXp11.3
Gene Typeprotein-coding
GO ID

GO:0000165

UniProtAcc

P10398


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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
369ARAFLZE4THumanEsophagusESCC4.91e-051.73e-010.0811
369ARAFLZE7THumanEsophagusESCC2.54e-021.88e-010.0667
369ARAFLZE8THumanEsophagusESCC2.89e-081.65e-010.067
369ARAFLZE20THumanEsophagusESCC3.73e-021.29e-010.0662
369ARAFLZE24THumanEsophagusESCC1.61e-052.26e-010.0596
369ARAFP1T-EHumanEsophagusESCC7.77e-052.17e-010.0875
369ARAFP2T-EHumanEsophagusESCC5.91e-324.51e-010.1177
369ARAFP4T-EHumanEsophagusESCC8.61e-103.02e-010.1323
369ARAFP5T-EHumanEsophagusESCC1.06e-112.03e-010.1327
369ARAFP8T-EHumanEsophagusESCC3.11e-326.07e-010.0889
369ARAFP9T-EHumanEsophagusESCC1.66e-112.77e-010.1131
369ARAFP10T-EHumanEsophagusESCC1.99e-152.61e-010.116
369ARAFP11T-EHumanEsophagusESCC1.26e-185.62e-010.1426
369ARAFP12T-EHumanEsophagusESCC7.89e-232.72e-010.1122
369ARAFP15T-EHumanEsophagusESCC4.20e-152.67e-010.1149
369ARAFP16T-EHumanEsophagusESCC1.33e-203.58e-010.1153
369ARAFP17T-EHumanEsophagusESCC2.20e-063.36e-010.1278
369ARAFP19T-EHumanEsophagusESCC1.12e-065.70e-010.1662
369ARAFP20T-EHumanEsophagusESCC2.78e-194.49e-010.1124
369ARAFP21T-EHumanEsophagusESCC3.52e-202.84e-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
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:001095913BreastIDCregulation of metal ion transport52/1434406/187231.76e-042.97e-0352
GO:0051924BreastIDCregulation of calcium ion transport32/1434255/187233.94e-033.22e-0232
GO:001095921BreastDCISregulation of metal ion transport50/1390406/187232.86e-044.22e-0350
GO:0010959ColorectumFAPregulation of metal ion transport83/2622406/187232.06e-042.96e-0383
GO:00109597EndometriumAEHregulation of metal ion transport66/2100406/187231.24e-031.07e-0266
GO:001095914EndometriumEECregulation of metal ion transport70/2168406/187234.12e-044.35e-0370
GO:0010498111EsophagusESCCproteasomal protein catabolic process369/8552490/187231.13e-411.80e-38369
GO:0043161111EsophagusESCCproteasome-mediated ubiquitin-dependent protein catabolic process312/8552412/187233.53e-364.48e-33312
GO:0042176111EsophagusESCCregulation of protein catabolic process280/8552391/187238.65e-262.39e-23280
GO:1903362111EsophagusESCCregulation of cellular protein catabolic process188/8552255/187235.12e-206.62e-18188
GO:1903050111EsophagusESCCregulation of proteolysis involved in cellular protein catabolic process163/8552221/187231.44e-171.27e-15163
GO:0061136111EsophagusESCCregulation of proteasomal protein catabolic process142/8552187/187232.40e-172.00e-15142
GO:0032434111EsophagusESCCregulation of proteasomal ubiquitin-dependent protein catabolic process107/8552134/187234.06e-162.93e-14107
GO:2000058111EsophagusESCCregulation of ubiquitin-dependent protein catabolic process125/8552164/187231.17e-157.76e-14125
GO:00182099EsophagusESCCpeptidyl-serine modification196/8552338/187233.07e-063.47e-05196
GO:001810515EsophagusESCCpeptidyl-serine phosphorylation184/8552315/187233.22e-063.61e-05184
GO:00319294EsophagusESCCTOR signaling79/8552126/187238.57e-056.21e-0479
GO:00320061EsophagusESCCregulation of TOR signaling63/8552104/187231.55e-037.29e-0363
GO:00331355EsophagusESCCregulation of peptidyl-serine phosphorylation81/8552144/187236.79e-032.48e-0281
GO:00331383EsophagusESCCpositive regulation of peptidyl-serine phosphorylation61/8552108/187231.54e-024.96e-0261
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check button Enriched KEGG pathways.
Pathway IDTissueDisease StageDescriptionGene RatioBg Ratiopvaluep.adjustqvalueCount
hsa0516111LiverHCCHepatitis B91/4020162/84651.56e-023.76e-022.09e-0291
hsa052211LiverHCCAcute myeloid leukemia41/402067/84651.64e-023.90e-022.17e-0241
hsa0501028Oral cavityOSCCAlzheimer disease244/3704384/84651.18e-153.60e-141.83e-14244
hsa0502228Oral cavityOSCCPathways of neurodegeneration - multiple diseases292/3704476/84651.60e-154.47e-142.28e-14292
hsa0520830Oral cavityOSCCChemical carcinogenesis - reactive oxygen species150/3704223/84656.45e-131.20e-116.11e-12150
hsa0521210Oral cavityOSCCPancreatic cancer60/370476/84653.32e-104.45e-092.26e-0960
hsa0521018Oral cavityOSCCColorectal cancer66/370486/84653.99e-104.95e-092.52e-0966
hsa051608Oral cavityOSCCHepatitis C103/3704157/84652.17e-081.96e-079.99e-08103
hsa0520526Oral cavityOSCCProteoglycans in cancer128/3704205/84654.00e-083.12e-071.59e-07128
hsa0522018Oral cavityOSCCChronic myeloid leukemia56/370476/84651.04e-077.43e-073.78e-0756
hsa051618Oral cavityOSCCHepatitis B103/3704162/84652.34e-071.51e-067.69e-07103
hsa0521116Oral cavityOSCCRenal cell carcinoma51/370469/84653.30e-072.05e-061.04e-0651
hsa040688Oral cavityOSCCFoxO signaling pathway85/3704131/84657.50e-074.33e-062.21e-0685
hsa0521510Oral cavityOSCCProstate cancer66/370497/84651.05e-065.89e-063.00e-0666
hsa015219Oral cavityOSCCEGFR tyrosine kinase inhibitor resistance54/370479/84658.11e-063.72e-051.89e-0554
hsa015226Oral cavityOSCCEndocrine resistance63/370498/84653.09e-051.31e-046.67e-0563
hsa049108Oral cavityOSCCInsulin signaling pathway83/3704137/84654.83e-052.00e-041.02e-0483
hsa0401014Oral cavityOSCCMAPK signaling pathway165/3704302/84657.11e-052.74e-041.40e-04165
hsa0481026Oral cavityOSCCRegulation of actin cytoskeleton129/3704229/84657.14e-052.74e-041.40e-04129
hsa0401216Oral cavityOSCCErbB signaling pathway55/370485/84657.46e-052.81e-041.43e-0455
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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
ARAFSNVMissense_Mutationnovelc.1089N>Cp.Lys363Asnp.K363Nprotein_codingdeleterious(0)probably_damaging(0.975)TCGA-5L-AAT1-01Breastbreast invasive carcinomaFemale<65III/IVHormone TherapyletrozolSD
ARAFSNVMissense_Mutationnovelc.766N>Cp.Thr256Prop.T256Pprotein_codingtolerated(0.42)benign(0)TCGA-A2-A0EW-01Breastbreast invasive carcinomaFemale<65III/IVChemotherapyadriamycinPD
ARAFSNVMissense_Mutationnovelc.486G>Tp.Gln162Hisp.Q162Hprotein_codingtolerated(0.12)benign(0.359)TCGA-AN-A046-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
ARAFSNVMissense_Mutationc.1213G>Ap.Asp405Asnp.D405Nprotein_codingdeleterious(0.02)possibly_damaging(0.872)TCGA-AN-A046-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
ARAFSNVMissense_Mutationrs764281834c.1745N>Ap.Arg582Glnp.R582Qprotein_codingdeleterious(0.02)benign(0.068)TCGA-AO-A03V-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapyfluorouracilSD
ARAFSNVMissense_Mutationrs777037087c.572G>Ap.Arg191Hisp.R191Hprotein_codingtolerated(0.35)benign(0.042)TCGA-AO-A128-01Breastbreast invasive carcinomaFemale<65I/IIChemotherapydoxorubicinSD
ARAFSNVMissense_Mutationrs62636600c.370N>Tp.Arg124Cysp.R124Cprotein_codingdeleterious(0.03)probably_damaging(0.999)TCGA-B6-A0RQ-01Breastbreast invasive carcinomaFemale>=65I/IIUnknownUnknownSD
ARAFSNVMissense_Mutationnovelc.766N>Cp.Thr256Prop.T256Pprotein_codingtolerated(0.42)benign(0)TCGA-BH-A1F5-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
ARAFSNVMissense_Mutationc.1810N>Ap.Ala604Thrp.A604Tprotein_codingtolerated(1)benign(0)TCGA-BH-A1F5-01Breastbreast invasive carcinomaFemale<65I/IIUnknownUnknownSD
ARAFSNVMissense_Mutationc.1496N>Ap.Gly499Glup.G499Eprotein_codingdeleterious(0)probably_damaging(1)TCGA-BH-A204-01Breastbreast 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
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMEsorafenibSORAFENIB24569458
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMEinhibitorLGX818ENCORAFENIB
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMEinhibitor310264724LY-3009120
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMESorafenibSORAFENIB
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMEinhibitorCHEMBL3545195LY-3009120
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMECobimetinibCOBIMETINIB
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMEinhibitorCHEMBL3348923MLN-2480
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMEinhibitor310264739LIFIRAFENIB
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMEinhibitor1096708-71-2
369ARAFCLINICALLY ACTIONABLE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYMEinhibitorXL281XL-281
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