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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:GAS6-GTPBP4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GAS6-GTPBP4
FusionPDB ID: 32533
FusionGDB2.0 ID: 32533
HgeneTgene
Gene symbol

GAS6

GTPBP4

Gene ID

2621

23560

Gene namegrowth arrest specific 6GTP binding protein 4
SynonymsAXLLG|AXSFCRFG|NGB|NOG1
Cytomap

13q34

10p15.3

Type of geneprotein-codingprotein-coding
Descriptiongrowth arrest-specific protein 6AXL receptor tyrosine kinase ligandAXL stimulatory factornucleolar GTP-binding protein 1G protein-binding protein CRFGGTP-binding protein NGBchronic renal failure gene protein
Modification date2020031320200313
UniProtAcc

Q14393

Main function of 5'-partner protein: FUNCTION: Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and MER whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. {ECO:0000269|PubMed:12364394, ECO:0000269|PubMed:18840707}.; FUNCTION: (Microbial infection) Can bridge virus envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry by apoptotic mimicry (PubMed:21501828). Plays a role in Dengue cell entry by apoptotic mimicry (PubMed:23084921). Plays a role in Vaccinia virus cell entry by apoptotic mimicry (PubMed:21501828). Plays a role in ebolavirus and marburgvirus cell entry by apoptotic mimicry (PubMed:17005688). {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:21501828, ECO:0000269|PubMed:23084921}.

Q9BZE4

Main function of 5'-partner protein: FUNCTION: Involved in the biogenesis of the 60S ribosomal subunit. {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000327773, ENST00000357389, 
ENST00000476291, ENST00000355761, 
ENST00000418959, ENST00000450766, 
ENST00000491635, ENST00000538293, 
ENST00000545048, ENST00000360803, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score21 X 12 X 12=30245 X 5 X 2=50
# samples 295
** MAII scorelog2(29/3024*10)=-3.38233333420614
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/50*10)=0
Fusion gene context

PubMed: GAS6 [Title/Abstract] AND GTPBP4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GAS6 [Title/Abstract] AND GTPBP4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GAS6(114566547)-GTPBP4(1060186), # samples:1
Anticipated loss of major functional domain due to fusion event.GAS6-GTPBP4 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.
GAS6-GTPBP4 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.
* 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
HgeneGAS6

GO:0001934

positive regulation of protein phosphorylation

7854420|16723520|20103767

HgeneGAS6

GO:0006468

protein phosphorylation

16359517

HgeneGAS6

GO:0006909

phagocytosis

21501828

HgeneGAS6

GO:0007165

signal transduction

7854420|18680538

HgeneGAS6

GO:0010628

positive regulation of gene expression

19657094

HgeneGAS6

GO:0010804

negative regulation of tumor necrosis factor-mediated signaling pathway

19657094

HgeneGAS6

GO:0018105

peptidyl-serine phosphorylation

18680538|20103767

HgeneGAS6

GO:0019064

fusion of virus membrane with host plasma membrane

21501828

HgeneGAS6

GO:0019079

viral genome replication

21501828

HgeneGAS6

GO:0032689

negative regulation of interferon-gamma production

18840707

HgeneGAS6

GO:0032715

negative regulation of interleukin-6 production

19657094

HgeneGAS6

GO:0032720

negative regulation of tumor necrosis factor production

19657094|20103767

HgeneGAS6

GO:0032825

positive regulation of natural killer cell differentiation

18840707

HgeneGAS6

GO:0033138

positive regulation of peptidyl-serine phosphorylation

16723520

HgeneGAS6

GO:0035457

cellular response to interferon-alpha

19657094

HgeneGAS6

GO:0035690

cellular response to drug

16359517

HgeneGAS6

GO:0035754

B cell chemotaxis

19922767

HgeneGAS6

GO:0043066

negative regulation of apoptotic process

19922767

HgeneGAS6

GO:0043154

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

16723520

HgeneGAS6

GO:0043277

apoptotic cell clearance

21501828

HgeneGAS6

GO:0043433

negative regulation of DNA-binding transcription factor activity

18680538

HgeneGAS6

GO:0043491

protein kinase B signaling

16723520|20103767

HgeneGAS6

GO:0045860

positive regulation of protein kinase activity

7854420

HgeneGAS6

GO:0045892

negative regulation of transcription, DNA-templated

18680538

HgeneGAS6

GO:0046718

viral entry into host cell

21501828

HgeneGAS6

GO:0046813

receptor-mediated virion attachment to host cell

21501828

HgeneGAS6

GO:0046827

positive regulation of protein export from nucleus

18680538

HgeneGAS6

GO:0048146

positive regulation of fibroblast proliferation

7854420|15184064

HgeneGAS6

GO:0050711

negative regulation of interleukin-1 secretion

20103767

HgeneGAS6

GO:0050766

positive regulation of phagocytosis

18395422

HgeneGAS6

GO:0051897

positive regulation of protein kinase B signaling

16359517|16723520|18680538

HgeneGAS6

GO:0061098

positive regulation of protein tyrosine kinase activity

20103767

HgeneGAS6

GO:0070168

negative regulation of biomineral tissue development

20048160

HgeneGAS6

GO:0070374

positive regulation of ERK1 and ERK2 cascade

15184064

HgeneGAS6

GO:0070588

calcium ion transmembrane transport

18395422

HgeneGAS6

GO:0071307

cellular response to vitamin K

16359517

HgeneGAS6

GO:0072659

protein localization to plasma membrane

16359517

HgeneGAS6

GO:0097241

hematopoietic stem cell migration to bone marrow

19922767

HgeneGAS6

GO:1900142

negative regulation of oligodendrocyte apoptotic process

16723520

HgeneGAS6

GO:1900165

negative regulation of interleukin-6 secretion

20103767

HgeneGAS6

GO:2000270

negative regulation of fibroblast apoptotic process

16359517

HgeneGAS6

GO:2000352

negative regulation of endothelial cell apoptotic process

16359517|18680538|18760998

HgeneGAS6

GO:2000510

positive regulation of dendritic cell chemotaxis

19657094

HgeneGAS6

GO:2000669

negative regulation of dendritic cell apoptotic process

19657094

TgeneGTPBP4

GO:0000079

regulation of cyclin-dependent protein serine/threonine kinase activity

17210637

TgeneGTPBP4

GO:0022408

negative regulation of cell-cell adhesion

17210637

TgeneGTPBP4

GO:0030336

negative regulation of cell migration

17210637

TgeneGTPBP4

GO:0031397

negative regulation of protein ubiquitination

17210637

TgeneGTPBP4

GO:0050821

protein stabilization

17210637



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/chr13:114566547/chr10:1060186)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across GAS6 (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 GTPBP4 (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 Amino Acid Sequences


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)
ENST00000357389GAS6chr13114566547-ENST00000360803GTPBP4chr101060186+348040884254262
ENST00000327773GAS6chr13114566547-ENST00000360803GTPBP4chr101060186+347440283648262

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
ENST00000357389ENST00000360803GAS6chr13114566547-GTPBP4chr101060186+0.001408830.9985911
ENST00000327773ENST00000360803GAS6chr13114566547-GTPBP4chr101060186+0.0013682020.9986318

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

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for GAS6-GTPBP4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide

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Potential FusionNeoAntigen Information of GAS6-GTPBP4 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Potential FusionNeoAntigen Information of GAS6-GTPBP4 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of GAS6-GTPBP4

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GAS6-GTPBP4

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score

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Vaccine Design for the FusionNeoAntigens of GAS6-GTPBP4

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of GAS6-GTPBP4

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample

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Potential target of CAR-T therapy development for GAS6-GTPBP4

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to GAS6-GTPBP4

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 GAS6-GTPBP4

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