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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:ST5-DENND5A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ST5-DENND5A
FusionPDB ID: 86969
FusionGDB2.0 ID: 86969
HgeneTgene
Gene symbol

ST5

DENND5A

Gene ID

6764

23258

Gene nameDENN domain containing 2BDENN domain containing 5A
SynonymsHTS1|ST5|p126EIEE49|RAB6IP1
Cytomap

11p15.4

11p15.4

Type of geneprotein-codingprotein-coding
Descriptionsuppression of tumorigenicity 5 proteinDENN/MADD domain containing 2BheLa tumor suppression 1DENN domain-containing protein 5ADENN/MADD domain containing 5ARAB6 interacting protein 1rab6-interacting protein 1
Modification date2020031320200313
UniProtAcc.

Q6IQ26

Main function of 5'-partner protein: FUNCTION: Guanine nucleotide exchange factor (GEF) which may activate RAB6A and RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Involved in the negative regulation of neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:G3V7Q0, ECO:0000269|PubMed:20937701}.
Ensembl transtripts involved in fusion geneENST idsENST00000313726, ENST00000357665, 
ENST00000526757, ENST00000530438, 
ENST00000534127, ENST00000526099, 
ENST00000530991, ENST00000531237, 
ENST00000534278, 
ENST00000526523, 
ENST00000328194, ENST00000527700, 
ENST00000530044, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 11 X 7=77015 X 15 X 6=1350
# samples 1216
** MAII scorelog2(12/770*10)=-2.68182403997375
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1350*10)=-3.07681559705083
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ST5 [Title/Abstract] AND DENND5A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ST5 [Title/Abstract] AND DENND5A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DENND5A(9163487)-ST5(8772272), # samples:1
ST5(8853103)-DENND5A(9171756), # samples:3
Anticipated loss of major functional domain due to fusion event.ST5-DENND5A 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.
ST5-DENND5A 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.
ST5-DENND5A seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
ST5-DENND5A seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
ST5-DENND5A 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


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/chr11:9163487/chr11:8772272)
- 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 ST5 (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 DENND5A (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)
ENST00000534127ST5chr118772168-ENST00000328194DENND5Achr119163655-16654661267154893
ENST00000534127ST5chr118772168-ENST00000530044DENND5Achr119163655-99746688661191
ENST00000534127ST5chr118772168-ENST00000527700DENND5Achr119163655-98646692064591
ENST00000313726ST5chr118772168-ENST00000328194DENND5Achr119163655-16284291230151193
ENST00000313726ST5chr118772168-ENST00000530044DENND5Achr119163655-96042984957491
ENST00000313726ST5chr118772168-ENST00000527700DENND5Achr119163655-94942988360891
ENST00000357665ST5chr118772168-ENST00000328194DENND5Achr119163655-14392401041132293
ENST00000357665ST5chr118772168-ENST00000530044DENND5Achr119163655-77124066038591
ENST00000357665ST5chr118772168-ENST00000527700DENND5Achr119163655-76024069441991
ENST00000530438ST5chr118772168-ENST00000328194DENND5Achr119163655-18046053740125
ENST00000530438ST5chr118772168-ENST00000530044DENND5Achr119163655-1136605102575091
ENST00000530438ST5chr118772168-ENST00000527700DENND5Achr119163655-11256053740125

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
ENST00000534127ENST00000328194ST5chr118772168-DENND5Achr119163655-0.555499260.44450068
ENST00000534127ENST00000530044ST5chr118772168-DENND5Achr119163655-0.299093630.70090634
ENST00000534127ENST00000527700ST5chr118772168-DENND5Achr119163655-0.121675770.8783243
ENST00000313726ENST00000328194ST5chr118772168-DENND5Achr119163655-0.682719350.3172807
ENST00000313726ENST00000530044ST5chr118772168-DENND5Achr119163655-0.45062840.5493716
ENST00000313726ENST00000527700ST5chr118772168-DENND5Achr119163655-0.158943180.8410568
ENST00000357665ENST00000328194ST5chr118772168-DENND5Achr119163655-0.691582140.3084178
ENST00000357665ENST00000530044ST5chr118772168-DENND5Achr119163655-0.2166190.783381
ENST00000357665ENST00000527700ST5chr118772168-DENND5Achr119163655-0.094059610.9059404
ENST00000530438ENST00000328194ST5chr118772168-DENND5Achr119163655-0.93229190.06770802
ENST00000530438ENST00000530044ST5chr118772168-DENND5Achr119163655-0.5154750.48452502
ENST00000530438ENST00000527700ST5chr118772168-DENND5Achr119163655-0.273805860.7261941

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 ST5-DENND5A

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 ST5-DENND5A 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 ST5-DENND5A 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 ST5-DENND5A

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 ST5-DENND5A

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 ST5-DENND5A

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 ST5-DENND5A

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 ST5-DENND5A

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 ST5-DENND5A

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 ST5-DENND5A

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