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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:STAT3-RAB5C

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: STAT3-RAB5C
FusionPDB ID: 87249
FusionGDB2.0 ID: 87249
HgeneTgene
Gene symbol

STAT3

RAB5C

Gene ID

6774

5878

Gene namesignal transducer and activator of transcription 3RAB5C, member RAS oncogene family
SynonymsADMIO|ADMIO1|APRF|HIESL1880|RAB5CL|RAB5L|RABL
Cytomap

17q21.2

17q21.2

Type of geneprotein-codingprotein-coding
Descriptionsignal transducer and activator of transcription 3DNA-binding protein APRFacute-phase response factorras-related protein Rab-5CRAB5C, member of RAS oncogene family
Modification date2020032920200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000389272, ENST00000404395, 
ENST00000588969, ENST00000264657, 
ENST00000585517, ENST00000590776, 
ENST00000346213, ENST00000393860, 
ENST00000547517, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 20 X 10=36008 X 7 X 6=336
# samples 2310
** MAII scorelog2(23/3600*10)=-3.96829114027266
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/336*10)=-1.74846123300404
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: STAT3 [Title/Abstract] AND RAB5C [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: STAT3 [Title/Abstract] AND RAB5C [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)STAT3(40475022)-RAB5C(40278866), # samples:1
Anticipated loss of major functional domain due to fusion event.STAT3-RAB5C 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.
STAT3-RAB5C 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.
STAT3-RAB5C 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.
STAT3-RAB5C 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.
STAT3-RAB5C seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
STAT3-RAB5C seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
STAT3-RAB5C seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
STAT3-RAB5C seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor 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
HgeneSTAT3

GO:0006355

regulation of transcription, DNA-templated

15664994|17344214

HgeneSTAT3

GO:0006606

protein import into nucleus

18234692

HgeneSTAT3

GO:0010507

negative regulation of autophagy

26962683

HgeneSTAT3

GO:0010628

positive regulation of gene expression

23820254

HgeneSTAT3

GO:0030522

intracellular receptor signaling pathway

17324931

HgeneSTAT3

GO:0032355

response to estradiol

12552091

HgeneSTAT3

GO:0032870

cellular response to hormone stimulus

12552091

HgeneSTAT3

GO:0033210

leptin-mediated signaling pathway

17344214

HgeneSTAT3

GO:0035278

miRNA mediated inhibition of translation

23820254

HgeneSTAT3

GO:0044320

cellular response to leptin stimulus

17344214

HgeneSTAT3

GO:0044321

response to leptin

17344214

HgeneSTAT3

GO:0045893

positive regulation of transcription, DNA-templated

19390056

HgeneSTAT3

GO:0045944

positive regulation of transcription by RNA polymerase II

17324931|27050391|31462771

HgeneSTAT3

GO:0051726

regulation of cell cycle

17344214

HgeneSTAT3

GO:0060396

growth hormone receptor signaling pathway

10925297

HgeneSTAT3

GO:0060397

JAK-STAT cascade involved in growth hormone signaling pathway

12552091

HgeneSTAT3

GO:0070102

interleukin-6-mediated signaling pathway

12359225|12552091|17324931|24429361

HgeneSTAT3

GO:1902895

positive regulation of pri-miRNA transcription by RNA polymerase II

19390056|23820254

HgeneSTAT3

GO:2000637

positive regulation of gene silencing by miRNA

23820254



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/chr17:40475022/chr17:40278866)
- 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 STAT3 (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 RAB5C (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)
ENST00000264657STAT3chr1740475022-ENST00000346213RAB5Cchr1740278866-321822013132298661
ENST00000264657STAT3chr1740475022-ENST00000393860RAB5Cchr1740278866-321422013132298661
ENST00000264657STAT3chr1740475022-ENST00000547517RAB5Cchr1740278866-252722013132298661
ENST00000585517STAT3chr1740475022-ENST00000346213RAB5Cchr1740278866-30702053302150706
ENST00000585517STAT3chr1740475022-ENST00000393860RAB5Cchr1740278866-30662053302150706
ENST00000585517STAT3chr1740475022-ENST00000547517RAB5Cchr1740278866-23792053302150706

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
ENST00000264657ENST00000346213STAT3chr1740475022-RAB5Cchr1740278866-0.0201937280.97980624
ENST00000264657ENST00000393860STAT3chr1740475022-RAB5Cchr1740278866-0.0202071010.97979295
ENST00000264657ENST00000547517STAT3chr1740475022-RAB5Cchr1740278866-0.0207642730.9792357
ENST00000585517ENST00000346213STAT3chr1740475022-RAB5Cchr1740278866-0.0204946510.9795053
ENST00000585517ENST00000393860STAT3chr1740475022-RAB5Cchr1740278866-0.0205262940.97947377
ENST00000585517ENST00000547517STAT3chr1740475022-RAB5Cchr1740278866-0.0215476570.9784524

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 STAT3-RAB5C

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 STAT3-RAB5C 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 STAT3-RAB5C 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 STAT3-RAB5C

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 STAT3-RAB5C

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 STAT3-RAB5C

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 STAT3-RAB5C

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 STAT3-RAB5C

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 STAT3-RAB5C

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 STAT3-RAB5C

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