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Center for Computational Systems Medicine level2
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:FOXK2-AMBRA1

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FOXK2-AMBRA1
FusionPDB ID: 31095
FusionGDB2.0 ID: 31095
HgeneTgene
Gene symbol

FOXK2

AMBRA1

Gene ID

3607

55626

Gene nameforkhead box K2autophagy and beclin 1 regulator 1
SynonymsILF|ILF-1|ILF1|nGTBPDCAF3|WDR94
Cytomap

17q25.3

11p11.2

Type of geneprotein-codingprotein-coding
Descriptionforkhead box protein K2FOXK1G/T-mismatch specific binding proteincellular transcription factor ILF-1interleukin enhancer-binding factor 1activating 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 date2020031320200313
UniProtAcc

Q01167

Q9C0C7

Ensembl transtripts involved in fusion geneENST idsENST00000335255, ENST00000529652, 
ENST00000529963, ENST00000458649, 
ENST00000528950, ENST00000533727, 
ENST00000534300, ENST00000298834, 
ENST00000314845, ENST00000426438, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score31 X 14 X 13=564217 X 12 X 8=1632
# samples 3419
** MAII scorelog2(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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneFOXK2

GO:0045892

negative regulation of transcription, DNA-templated

20810654|25451922

HgeneFOXK2

GO:0045893

positive regulation of transcription, DNA-templated

22083952

HgeneFOXK2

GO:0045944

positive regulation of transcription by RNA polymerase II

9065434

TgeneAMBRA1

GO:0000423

mitophagy

21753002

TgeneAMBRA1

GO:0043552

positive regulation of phosphatidylinositol 3-kinase activity

21753002

TgeneAMBRA1

GO:0098780

response to mitochondrial depolarisation

21753002


check buttonFusion gene breakpoints across FOXK2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across AMBRA1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4CESCTCGA-VS-A9V0-01AFOXK2chr17

80478183

-AMBRA1chr11

46419493

-
ChimerDB4CESCTCGA-VS-A9V0-01AFOXK2chr17

80478183

+AMBRA1chr11

46419493

-
ChimerDB4CESCTCGA-VS-A9V0FOXK2chr17

80478183

+AMBRA1chr11

46419493

-


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Fusion ORF Analysis


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000335255FOXK2chr1780478183+ENST00000298834AMBRA1chr1146419493-21235934451086213
ENST00000335255FOXK2chr1780478183+ENST00000426438AMBRA1chr1146419493-21235934451086213
ENST00000335255FOXK2chr1780478183+ENST00000314845AMBRA1chr1146419493-21235934451086213

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000335255ENST00000298834FOXK2chr1780478183+AMBRA1chr1146419493-0.309833440.6901666
ENST00000335255ENST00000426438FOXK2chr1780478183+AMBRA1chr1146419493-0.309833440.6901666
ENST00000335255ENST00000314845FOXK2chr1780478183+AMBRA1chr1146419493-0.309833440.6901666

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>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


check button Four levels of functional features of fusion genes
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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
FOXK2

Q01167

AMBRA1

Q9C0C7

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}.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneFOXK2chr17:80478183chr11:46419493ENST00000335255+1910_93139.66666666666666661.0Compositional biasNote=Gly-rich
HgeneFOXK2chr17:80478183chr11:46419493ENST00000335255+1954_128139.66666666666666661.0DomainFHA

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneFOXK2chr17:80478183chr11:46419493ENST00000335255+19258_353139.66666666666666661.0DNA bindingFork-head
HgeneFOXK2chr17:80478183chr11:46419493ENST00000335255+19300_318139.66666666666666661.0RegionDNA-binding%3B major groove
HgeneFOXK2chr17:80478183chr11:46419493ENST00000335255+19328_332139.66666666666666661.0RegionDNA-binding%3B minor groove
HgeneFOXK2chr17:80478183chr11:46419493ENST00000335255+19348_353139.66666666666666661.0RegionDNA-binding%3B minor groove
TgeneAMBRA1chr17:80478183chr11:46419493ENST000002988341517268_2771074.33333333333331239.0Compositional biasNote=Poly-Pro
TgeneAMBRA1chr17:80478183chr11:46419493ENST000002988341517592_6391074.33333333333331239.0Compositional biasNote=Ser-rich
TgeneAMBRA1chr17:80478183chr11:46419493ENST000003148451719268_2771044.33333333333331209.0Compositional biasNote=Poly-Pro
TgeneAMBRA1chr17:80478183chr11:46419493ENST000003148451719592_6391044.33333333333331209.0Compositional biasNote=Ser-rich
TgeneAMBRA1chr17:80478183chr11:46419493ENST000004264381517268_2771105.33333333333331270.0Compositional biasNote=Poly-Pro
TgeneAMBRA1chr17:80478183chr11:46419493ENST000004264381517592_6391105.33333333333331270.0Compositional biasNote=Ser-rich
TgeneAMBRA1chr17:80478183chr11:46419493ENST000004586491618268_2771134.33333333333331299.0Compositional biasNote=Poly-Pro
TgeneAMBRA1chr17:80478183chr11:46419493ENST000004586491618592_6391134.33333333333331299.0Compositional biasNote=Ser-rich
TgeneAMBRA1chr17:80478183chr11:46419493ENST000005289501517268_2771105.33333333333331270.0Compositional biasNote=Poly-Pro
TgeneAMBRA1chr17:80478183chr11:46419493ENST000005289501517592_6391105.33333333333331270.0Compositional biasNote=Ser-rich
TgeneAMBRA1chr17:80478183chr11:46419493ENST000005337271618268_2771015.33333333333341180.0Compositional biasNote=Poly-Pro
TgeneAMBRA1chr17:80478183chr11:46419493ENST000005337271618592_6391015.33333333333341180.0Compositional biasNote=Ser-rich
TgeneAMBRA1chr17:80478183chr11:46419493ENST000005343001517268_2771074.33333333333331239.0Compositional biasNote=Poly-Pro
TgeneAMBRA1chr17:80478183chr11:46419493ENST000005343001517592_6391074.33333333333331239.0Compositional biasNote=Ser-rich
TgeneAMBRA1chr17:80478183chr11:46419493ENST000002988341517135_1751074.33333333333331239.0RepeatNote=WD 3
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000298834151751_901074.33333333333331239.0RepeatNote=WD 1
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000298834151793_1331074.33333333333331239.0RepeatNote=WD 2
TgeneAMBRA1chr17:80478183chr11:46419493ENST000003148451719135_1751044.33333333333331209.0RepeatNote=WD 3
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000314845171951_901044.33333333333331209.0RepeatNote=WD 1
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000314845171993_1331044.33333333333331209.0RepeatNote=WD 2
TgeneAMBRA1chr17:80478183chr11:46419493ENST000004264381517135_1751105.33333333333331270.0RepeatNote=WD 3
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000426438151751_901105.33333333333331270.0RepeatNote=WD 1
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000426438151793_1331105.33333333333331270.0RepeatNote=WD 2
TgeneAMBRA1chr17:80478183chr11:46419493ENST000004586491618135_1751134.33333333333331299.0RepeatNote=WD 3
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000458649161851_901134.33333333333331299.0RepeatNote=WD 1
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000458649161893_1331134.33333333333331299.0RepeatNote=WD 2
TgeneAMBRA1chr17:80478183chr11:46419493ENST000005289501517135_1751105.33333333333331270.0RepeatNote=WD 3
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000528950151751_901105.33333333333331270.0RepeatNote=WD 1
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000528950151793_1331105.33333333333331270.0RepeatNote=WD 2
TgeneAMBRA1chr17:80478183chr11:46419493ENST000005337271618135_1751015.33333333333341180.0RepeatNote=WD 3
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000533727161851_901015.33333333333341180.0RepeatNote=WD 1
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000533727161893_1331015.33333333333341180.0RepeatNote=WD 2
TgeneAMBRA1chr17:80478183chr11:46419493ENST000005343001517135_1751074.33333333333331239.0RepeatNote=WD 3
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000534300151751_901074.33333333333331239.0RepeatNote=WD 1
TgeneAMBRA1chr17:80478183chr11:46419493ENST00000534300151793_1331074.33333333333331239.0RepeatNote=WD 2


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Fusion Protein Structures

check button PDB and CIF files of the predicted fusion proteins
* 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)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file >>>309_FOXK2_80478183_AMBRA1_46419493_ranked_0.pdbFOXK28047818380478183ENST00000314845AMBRA1chr1146419493-
MAGPLRSCRPRSPGPTPAATSTCAAWARTGYSWTACSRGAGRRRCSCRACEGSEYGASGEDALSRIQRLMAEGGMTAVVQREQSTTMASM
GGFGNNIIVSHRIHRSSQTGTEPGAAHTSSPQPSTSRGLLPEAGQLAERGLSPRTASWDQPGTPGREPTQPTLPSSSPVPIPVSLPSAEG
213


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
FOXK2_pLDDT.png
all structure
all structure
AMBRA1_pLDDT.png
all structure
all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
all structure


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Ramachandran Plot of Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.
Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
FOXK2
AMBRA1


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to FOXK2-AMBRA1


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to FOXK2-AMBRA1


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource