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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:ITGB4-SLC16A5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ITGB4-SLC16A5
FusionPDB ID: 40550
FusionGDB2.0 ID: 40550
HgeneTgene
Gene symbol

ITGB4

SLC16A5

Gene ID

3691

9121

Gene nameintegrin subunit beta 4solute carrier family 16 member 5
SynonymsCD104|GP150MCT5|MCT6
Cytomap

17q25.1

17q25.1

Type of geneprotein-codingprotein-coding
Descriptionintegrin beta-4CD104 antigenmonocarboxylate transporter 6monocarboxylate transporter 5solute carrier family 16 (monocarboxylate transporter), member 5solute carrier family 16 (monocarboxylic acid transporters), member 5solute carrier family 16, member 5 (monocarboxylic acid tran
Modification date2020032920200313
UniProtAcc

P16144

Main function of 5'-partner protein: FUNCTION: Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000200181, ENST00000339591, 
ENST00000449880, ENST00000450894, 
ENST00000579662, ENST00000584558, 
ENST00000329783, ENST00000450736, 
ENST00000538213, ENST00000585293, 
ENST00000580123, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 19 X 10=43707 X 6 X 5=210
# samples 298
** MAII scorelog2(29/4370*10)=-3.91350847437303
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/210*10)=-1.39231742277876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ITGB4 [Title/Abstract] AND SLC16A5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ITGB4 [Title/Abstract] AND SLC16A5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ITGB4(73747192)-SLC16A5(73094133), # samples:3
Anticipated loss of major functional domain due to fusion event.ITGB4-SLC16A5 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.
ITGB4-SLC16A5 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.
ITGB4-SLC16A5 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.
ITGB4-SLC16A5 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
HgeneITGB4

GO:0009611

response to wounding

19403692

HgeneITGB4

GO:0031581

hemidesmosome assembly

12482924



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/chr17:73747192/chr17:73094133)
- 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 ITGB4 (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 SLC16A5 (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)
ENST00000579662ITGB4chr1773747192+ENST00000580123SLC16A5chr1773094133+5487403924653571703
ENST00000339591ITGB4chr1773747192+ENST00000580123SLC16A5chr1773094133+5428398016352981711
ENST00000200181ITGB4chr1773747192+ENST00000580123SLC16A5chr1773094133+5428398016352981711
ENST00000450894ITGB4chr1773747192+ENST00000580123SLC16A5chr1773094133+5367391910252371711
ENST00000449880ITGB4chr1773747192+ENST00000580123SLC16A5chr1773094133+52493801851191703

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
ENST00000579662ENST00000580123ITGB4chr1773747192+SLC16A5chr1773094133+0.0036704130.9963296
ENST00000339591ENST00000580123ITGB4chr1773747192+SLC16A5chr1773094133+0.0036566040.99634343
ENST00000200181ENST00000580123ITGB4chr1773747192+SLC16A5chr1773094133+0.0036566040.99634343
ENST00000450894ENST00000580123ITGB4chr1773747192+SLC16A5chr1773094133+0.0034798720.99652016
ENST00000449880ENST00000580123ITGB4chr1773747192+SLC16A5chr1773094133+0.0030699950.99693006

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 ITGB4-SLC16A5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ITGB4chr1773747192SLC16A5chr177309413338011265YEVCYGLVNDDNRPLCSILVGRFGCR
ITGB4chr1773747192SLC16A5chr177309413339191273YEVCYGLVNDDNRPLCSILVGRFGCR
ITGB4chr1773747192SLC16A5chr177309413339801273YEVCYGLVNDDNRPLCSILVGRFGCR
ITGB4chr1773747192SLC16A5chr177309413340391265YEVCYGLVNDDNRPLCSILVGRFGCR

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Potential FusionNeoAntigen Information of ITGB4-SLC16A5 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.
ITGB4-SLC16A5_73747192_73094133.msa

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)
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-A74:09RPLCSILVGR0.88480.55031222
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-A74:03RPLCSILVGR0.88480.55031222
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-A74:11RPLCSILVGR0.88480.55031222
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-C03:08LVNDDNRPL0.99780.9098615
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-C03:19LVNDDNRPL0.99680.9876615
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-C03:07LVNDDNRPL0.99630.9521615
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-C03:03LVNDDNRPL0.99810.9874615
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-C03:04LVNDDNRPL0.99810.9874615
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-C03:05LVNDDNRPL0.99330.9241615
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-C03:06LVNDDNRPL0.97550.9875615
ITGB4-SLC16A5chr1773747192chr17730941333980HLA-A74:01RPLCSILVGR0.88480.55031222

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Potential FusionNeoAntigen Information of ITGB4-SLC16A5 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 ITGB4-SLC16A5

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.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
5785LVNDDNRPLCSILVITGB4SLC16A5chr1773747192chr17730941333980

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ITGB4-SLC16A5

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
HLA-B14:023BVN5785LVNDDNRPLCSILV-7.15543-7.26883
HLA-B14:023BVN5785LVNDDNRPLCSILV-4.77435-5.80965
HLA-B52:013W395785LVNDDNRPLCSILV-6.80875-6.92215
HLA-B52:013W395785LVNDDNRPLCSILV-4.20386-5.23916
HLA-A11:014UQ25785LVNDDNRPLCSILV-7.5194-8.5547
HLA-A11:014UQ25785LVNDDNRPLCSILV-6.9601-7.0735
HLA-A24:025HGA5785LVNDDNRPLCSILV-7.52403-7.63743
HLA-A24:025HGA5785LVNDDNRPLCSILV-5.82433-6.85963
HLA-B27:056PYJ5785LVNDDNRPLCSILV-3.28285-4.31815
HLA-B44:053DX85785LVNDDNRPLCSILV-5.91172-6.94702
HLA-B44:053DX85785LVNDDNRPLCSILV-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ITGB4-SLC16A5

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
ITGB4-SLC16A5chr1773747192chr17730941331222RPLCSILVGRACCGGCCCCTGTGCAGCATCCTGGTGGGAC
ITGB4-SLC16A5chr1773747192chr1773094133615LVNDDNRPLGCCTGGTCAACGATGACAACCGGCCCC

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 ITGB4-SLC16A5

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
BRCAITGB4-SLC16A5chr1773747192ENST00000200181chr1773094133ENST00000580123TCGA-C8-A26X-01A

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Potential target of CAR-T therapy development for ITGB4-SLC16A5

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
HgeneITGB4chr17:73747192chr17:73094133ENST00000200181+3040711_73312641823.0TransmembraneHelical
HgeneITGB4chr17:73747192chr17:73094133ENST00000339591+3040711_73312641806.0TransmembraneHelical
HgeneITGB4chr17:73747192chr17:73094133ENST00000449880+2939711_73312641806.0TransmembraneHelical
HgeneITGB4chr17:73747192chr17:73094133ENST00000450894+3039711_73312641753.0TransmembraneHelical
HgeneITGB4chr17:73747192chr17:73094133ENST00000579662+3039711_73312641753.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000032978327111_1310506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000032978327138_1580506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000032978327172_1920506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000032978327240_2600506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000032978327275_2950506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000032978327306_3260506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000032978327330_3500506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000032978327368_3880506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000032978327397_4170506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST000003297832781_1010506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000045073616111_1310506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000045073616138_1580506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000045073616172_1920506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000045073616240_2600506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000045073616275_2950506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000045073616306_3260506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000045073616330_3500506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000045073616368_3880506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000045073616397_4170506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST000004507361681_1010506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000058012327111_1310506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000058012327138_1580506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000058012327172_1920506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000058012327240_2600506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000058012327275_2950506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000058012327306_3260506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000058012327330_3500506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000058012327368_3880506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST0000058012327397_4170506.0TransmembraneHelical
TgeneSLC16A5chr17:73747192chr17:73094133ENST000005801232781_1010506.0TransmembraneHelical

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
ITGB4chr1773747192ENST00000200181SLC16A5chr1773094133ENST00000580123
ITGB4chr1773747192ENST00000449880SLC16A5chr1773094133ENST00000580123

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Related Drugs to ITGB4-SLC16A5

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 ITGB4-SLC16A5

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