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Fusion Protein:FOXK2-AMBRA1 |
Fusion Protein Summary |
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Fusion partner gene information | Fusion gene name: FOXK2-AMBRA1 | FusionPDB ID: 31095 | FusionGDB2.0 ID: 31095 | Hgene | Tgene | Gene symbol | FOXK2 | AMBRA1 | Gene ID | 3607 | 55626 |
Gene name | forkhead box K2 | autophagy and beclin 1 regulator 1 | |
Synonyms | ILF|ILF-1|ILF1|nGTBP | DCAF3|WDR94 | |
Cytomap | 17q25.3 | 11p11.2 | |
Type of gene | protein-coding | protein-coding | |
Description | forkhead box protein K2FOXK1G/T-mismatch specific binding proteincellular transcription factor ILF-1interleukin enhancer-binding factor 1 | activating molecule in BECN1-regulated autophagy protein 1DDB1 and CUL4 associated factor 3WD repeat domain 94activating molecule in beclin-1-regulated autophagyautophagy/beclin-1 regulator 1 | |
Modification date | 20200313 | 20200313 | |
UniProtAcc | Q01167 | Q9C0C7 | |
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000335255, ENST00000529652, | ENST00000529963, ENST00000458649, ENST00000528950, ENST00000533727, ENST00000534300, ENST00000298834, ENST00000314845, ENST00000426438, |
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 31 X 14 X 13=5642 | 17 X 12 X 8=1632 |
# samples | 34 | 19 | |
** MAII score | log2(34/5642*10)=-4.05260001444787 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(19/1632*10)=-3.10256973364055 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
Context (manual curation of fusion genes in FusionPDB) | PubMed: FOXK2 [Title/Abstract] AND AMBRA1 [Title/Abstract] AND fusion [Title/Abstract] | ||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | FOXK2(80478183)-AMBRA1(46419493), # samples:3 | ||
Anticipated loss of major functional domain due to fusion event. | FOXK2-AMBRA1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. FOXK2-AMBRA1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. FOXK2-AMBRA1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. FOXK2-AMBRA1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. FOXK2-AMBRA1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. FOXK2-AMBRA1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF. FOXK2-AMBRA1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF. |
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
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Partner | Gene | GO ID | GO term | PubMed ID |
Hgene | FOXK2 | GO:0045892 | negative regulation of transcription, DNA-templated | 20810654|25451922 |
Hgene | FOXK2 | GO:0045893 | positive regulation of transcription, DNA-templated | 22083952 |
Hgene | FOXK2 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 9065434 |
Tgene | AMBRA1 | GO:0000423 | mitophagy | 21753002 |
Tgene | AMBRA1 | GO:0043552 | positive regulation of phosphatidylinositol 3-kinase activity | 21753002 |
Tgene | AMBRA1 | GO:0098780 | response to mitochondrial depolarisation | 21753002 |
![]() * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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![]() * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Fusion Gene Sample Information |
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![]() * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
ChimerDB4 | CESC | TCGA-VS-A9V0-01A | FOXK2 | chr17 | 80478183 | - | AMBRA1 | chr11 | 46419493 | - |
ChimerDB4 | CESC | TCGA-VS-A9V0-01A | FOXK2 | chr17 | 80478183 | + | AMBRA1 | chr11 | 46419493 | - |
ChimerDB4 | CESC | TCGA-VS-A9V0 | FOXK2 | chr17 | 80478183 | + | AMBRA1 | chr11 | 46419493 | - |
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Fusion ORF Analysis |
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Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
ENST00000335255 | FOXK2 | chr17 | 80478183 | + | ENST00000298834 | AMBRA1 | chr11 | 46419493 | - | 2123 | 593 | 445 | 1086 | 213 |
ENST00000335255 | FOXK2 | chr17 | 80478183 | + | ENST00000426438 | AMBRA1 | chr11 | 46419493 | - | 2123 | 593 | 445 | 1086 | 213 |
ENST00000335255 | FOXK2 | chr17 | 80478183 | + | ENST00000314845 | AMBRA1 | chr11 | 46419493 | - | 2123 | 593 | 445 | 1086 | 213 |
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Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
ENST00000335255 | ENST00000298834 | FOXK2 | chr17 | 80478183 | + | AMBRA1 | chr11 | 46419493 | - | 0.30983344 | 0.6901666 |
ENST00000335255 | ENST00000426438 | FOXK2 | chr17 | 80478183 | + | AMBRA1 | chr11 | 46419493 | - | 0.30983344 | 0.6901666 |
ENST00000335255 | ENST00000314845 | FOXK2 | chr17 | 80478183 | + | AMBRA1 | chr11 | 46419493 | - | 0.30983344 | 0.6901666 |
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Fusion Amino Acid Sequences |
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>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >31095_31095_1_FOXK2-AMBRA1_FOXK2_chr17_80478183_ENST00000335255_AMBRA1_chr11_46419493_ENST00000298834_length(amino acids)=213AA_BP=50 MAGPLRSCRPRSPGPTPAATSTCAAWARTGYSWTACSRGAGRRRCSCRACEGSEYGASGEDALSRIQRLMAEGGMTAVVQREQSTTMASM GGFGNNIIVSHRIHRSSQTGTEPGAAHTSSPQPSTSRGLLPEAGQLAERGLSPRTASWDQPGTPGREPTQPTLPSSSPVPIPVSLPSAEG -------------------------------------------------------------- >31095_31095_2_FOXK2-AMBRA1_FOXK2_chr17_80478183_ENST00000335255_AMBRA1_chr11_46419493_ENST00000314845_length(amino acids)=213AA_BP=50 MAGPLRSCRPRSPGPTPAATSTCAAWARTGYSWTACSRGAGRRRCSCRACEGSEYGASGEDALSRIQRLMAEGGMTAVVQREQSTTMASM GGFGNNIIVSHRIHRSSQTGTEPGAAHTSSPQPSTSRGLLPEAGQLAERGLSPRTASWDQPGTPGREPTQPTLPSSSPVPIPVSLPSAEG -------------------------------------------------------------- >31095_31095_3_FOXK2-AMBRA1_FOXK2_chr17_80478183_ENST00000335255_AMBRA1_chr11_46419493_ENST00000426438_length(amino acids)=213AA_BP=50 MAGPLRSCRPRSPGPTPAATSTCAAWARTGYSWTACSRGAGRRRCSCRACEGSEYGASGEDALSRIQRLMAEGGMTAVVQREQSTTMASM GGFGNNIIVSHRIHRSSQTGTEPGAAHTSSPQPSTSRGLLPEAGQLAERGLSPRTASWDQPGTPGREPTQPTLPSSSPVPIPVSLPSAEG -------------------------------------------------------------- |
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Fusion Protein Functional Features |
![]() Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:80478183/chr11:46419493) - FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels. - How to search 1. Put your fusion gene symbol. 2. Press the tab key until there will be shown the breakpoint information filled. 4. Go down and press 'Search' tab twice. 4. Go down to have the hyperlink of the search result. 5. Click the hyperlink. 6. See the FGviewer result for your fusion gene. |
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Hgene | Tgene |
FOXK2 | AMBRA1 |
FUNCTION: Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:22083952, PubMed:25451922). Together with FOXK1, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Together with FOXK1, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). In addition to the 5'-GTAAACA-3' DNA motif, also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates with JUN/AP-1 to activate transcription (PubMed:22083952). Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence (PubMed:20097901). Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390). Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027). {ECO:0000250|UniProtKB:Q3UCQ1, ECO:0000269|PubMed:1339390, ECO:0000269|PubMed:1909027, ECO:0000269|PubMed:20097901, ECO:0000269|PubMed:22083952, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:25805136}. | FUNCTION: Regulates autophagy and development of the nervous system. Involved in autophagy in controlling protein turnover during neuronal development, and in regulating normal cell survival and proliferation (By similarity). {ECO:0000250}. |
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- Retained protein feature among the 13 regional features. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
Hgene | FOXK2 | chr17:80478183 | chr11:46419493 | ENST00000335255 | + | 1 | 9 | 10_93 | 139.66666666666666 | 661.0 | Compositional bias | Note=Gly-rich |
Hgene | FOXK2 | chr17:80478183 | chr11:46419493 | ENST00000335255 | + | 1 | 9 | 54_128 | 139.66666666666666 | 661.0 | Domain | FHA |
- Not-retained protein feature among the 13 regional features. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
Hgene | FOXK2 | chr17:80478183 | chr11:46419493 | ENST00000335255 | + | 1 | 9 | 258_353 | 139.66666666666666 | 661.0 | DNA binding | Fork-head |
Hgene | FOXK2 | chr17:80478183 | chr11:46419493 | ENST00000335255 | + | 1 | 9 | 300_318 | 139.66666666666666 | 661.0 | Region | DNA-binding%3B major groove |
Hgene | FOXK2 | chr17:80478183 | chr11:46419493 | ENST00000335255 | + | 1 | 9 | 328_332 | 139.66666666666666 | 661.0 | Region | DNA-binding%3B minor groove |
Hgene | FOXK2 | chr17:80478183 | chr11:46419493 | ENST00000335255 | + | 1 | 9 | 348_353 | 139.66666666666666 | 661.0 | Region | DNA-binding%3B minor groove |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000298834 | 15 | 17 | 268_277 | 1074.3333333333333 | 1239.0 | Compositional bias | Note=Poly-Pro | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000298834 | 15 | 17 | 592_639 | 1074.3333333333333 | 1239.0 | Compositional bias | Note=Ser-rich | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000314845 | 17 | 19 | 268_277 | 1044.3333333333333 | 1209.0 | Compositional bias | Note=Poly-Pro | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000314845 | 17 | 19 | 592_639 | 1044.3333333333333 | 1209.0 | Compositional bias | Note=Ser-rich | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000426438 | 15 | 17 | 268_277 | 1105.3333333333333 | 1270.0 | Compositional bias | Note=Poly-Pro | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000426438 | 15 | 17 | 592_639 | 1105.3333333333333 | 1270.0 | Compositional bias | Note=Ser-rich | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000458649 | 16 | 18 | 268_277 | 1134.3333333333333 | 1299.0 | Compositional bias | Note=Poly-Pro | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000458649 | 16 | 18 | 592_639 | 1134.3333333333333 | 1299.0 | Compositional bias | Note=Ser-rich | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000528950 | 15 | 17 | 268_277 | 1105.3333333333333 | 1270.0 | Compositional bias | Note=Poly-Pro | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000528950 | 15 | 17 | 592_639 | 1105.3333333333333 | 1270.0 | Compositional bias | Note=Ser-rich | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000533727 | 16 | 18 | 268_277 | 1015.3333333333334 | 1180.0 | Compositional bias | Note=Poly-Pro | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000533727 | 16 | 18 | 592_639 | 1015.3333333333334 | 1180.0 | Compositional bias | Note=Ser-rich | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000534300 | 15 | 17 | 268_277 | 1074.3333333333333 | 1239.0 | Compositional bias | Note=Poly-Pro | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000534300 | 15 | 17 | 592_639 | 1074.3333333333333 | 1239.0 | Compositional bias | Note=Ser-rich | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000298834 | 15 | 17 | 135_175 | 1074.3333333333333 | 1239.0 | Repeat | Note=WD 3 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000298834 | 15 | 17 | 51_90 | 1074.3333333333333 | 1239.0 | Repeat | Note=WD 1 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000298834 | 15 | 17 | 93_133 | 1074.3333333333333 | 1239.0 | Repeat | Note=WD 2 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000314845 | 17 | 19 | 135_175 | 1044.3333333333333 | 1209.0 | Repeat | Note=WD 3 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000314845 | 17 | 19 | 51_90 | 1044.3333333333333 | 1209.0 | Repeat | Note=WD 1 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000314845 | 17 | 19 | 93_133 | 1044.3333333333333 | 1209.0 | Repeat | Note=WD 2 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000426438 | 15 | 17 | 135_175 | 1105.3333333333333 | 1270.0 | Repeat | Note=WD 3 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000426438 | 15 | 17 | 51_90 | 1105.3333333333333 | 1270.0 | Repeat | Note=WD 1 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000426438 | 15 | 17 | 93_133 | 1105.3333333333333 | 1270.0 | Repeat | Note=WD 2 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000458649 | 16 | 18 | 135_175 | 1134.3333333333333 | 1299.0 | Repeat | Note=WD 3 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000458649 | 16 | 18 | 51_90 | 1134.3333333333333 | 1299.0 | Repeat | Note=WD 1 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000458649 | 16 | 18 | 93_133 | 1134.3333333333333 | 1299.0 | Repeat | Note=WD 2 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000528950 | 15 | 17 | 135_175 | 1105.3333333333333 | 1270.0 | Repeat | Note=WD 3 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000528950 | 15 | 17 | 51_90 | 1105.3333333333333 | 1270.0 | Repeat | Note=WD 1 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000528950 | 15 | 17 | 93_133 | 1105.3333333333333 | 1270.0 | Repeat | Note=WD 2 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000533727 | 16 | 18 | 135_175 | 1015.3333333333334 | 1180.0 | Repeat | Note=WD 3 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000533727 | 16 | 18 | 51_90 | 1015.3333333333334 | 1180.0 | Repeat | Note=WD 1 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000533727 | 16 | 18 | 93_133 | 1015.3333333333334 | 1180.0 | Repeat | Note=WD 2 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000534300 | 15 | 17 | 135_175 | 1074.3333333333333 | 1239.0 | Repeat | Note=WD 3 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000534300 | 15 | 17 | 51_90 | 1074.3333333333333 | 1239.0 | Repeat | Note=WD 1 | |
Tgene | AMBRA1 | chr17:80478183 | chr11:46419493 | ENST00000534300 | 15 | 17 | 93_133 | 1074.3333333333333 | 1239.0 | Repeat | Note=WD 2 |
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Fusion Protein Structures |
![]() * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
Fusion protein PDB link (fusion AA seq ID in FusionPDB) | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | AA seq | Len(AA seq) |
PDB file >>>309_FOXK2_80478183_AMBRA1_46419493_ranked_0.pdb | FOXK2 | 80478183 | 80478183 | ENST00000314845 | AMBRA1 | chr11 | 46419493 | - | MAGPLRSCRPRSPGPTPAATSTCAAWARTGYSWTACSRGAGRRRCSCRACEGSEYGASGEDALSRIQRLMAEGGMTAVVQREQSTTMASM GGFGNNIIVSHRIHRSSQTGTEPGAAHTSSPQPSTSRGLLPEAGQLAERGLSPRTASWDQPGTPGREPTQPTLPSSSPVPIPVSLPSAEG | 213 |
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pLDDT score distribution |
![]() * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
FOXK2_pLDDT.png![]() |
AMBRA1_pLDDT.png![]() |
![]() * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
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Ramachandran Plot of Fusion Protein Structure |
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Fusion AA seq ID in FusionPDB and their Ramachandran plots |
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Fusion Protein-Protein Interaction |
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Gene | PPI interactors |
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Gene | STRING network |
FOXK2 | |
AMBRA1 |
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Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
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Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs to FOXK2-AMBRA1 |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to FOXK2-AMBRA1 |
![]() (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Disease | Source | PMID |
![]() (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |