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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:LTK-ITGB4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LTK-ITGB4
FusionPDB ID: 50316
FusionGDB2.0 ID: 50316
HgeneTgene
Gene symbol

LTK

ITGB4

Gene ID

4058

3691

Gene nameleukocyte receptor tyrosine kinaseintegrin subunit beta 4
SynonymsTYK1CD104|GP150
Cytomap

15q15.1

17q25.1

Type of geneprotein-codingprotein-coding
Descriptionleukocyte tyrosine kinase receptorprotein tyrosine kinase 1integrin beta-4CD104 antigen
Modification date2020032020200329
UniProtAcc

P29376

Main function of 5'-partner protein: FUNCTION: Receptor with a tyrosine-protein kinase activity. The exact function of this protein is not known. Studies with chimeric proteins (replacing its extracellular region with that of several known growth factor receptors, such as EGFR and CSFIR) demonstrate its ability to promote growth and specifically neurite outgrowth, and cell survival. Signaling appears to involve the PI3 kinase pathway. Involved in regulation of the secretory pathway involving endoplasmic reticulum (ER) export sites (ERESs) and ER to Golgi transport. {ECO:0000269|PubMed:20548102}.

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 idsENST00000263800, ENST00000355166, 
ENST00000453182, ENST00000561619, 
ENST00000584558, ENST00000200181, 
ENST00000339591, ENST00000449880, 
ENST00000450894, ENST00000579662, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score1 X 1 X 1=18 X 8 X 7=448
# samples 19
** MAII scorelog2(1/1*10)=3.32192809488736log2(9/448*10)=-2.31550182572793
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LTK(41799292)-ITGB4(73746760), # samples:1
Anticipated loss of major functional domain due to fusion event.LTK-ITGB4 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.
LTK-ITGB4 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.
LTK-ITGB4 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.
LTK-ITGB4 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.
LTK-ITGB4 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
LTK-ITGB4 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
LTK-ITGB4 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
LTK-ITGB4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
HgeneLTK

GO:0006468

protein phosphorylation

9223670

HgeneLTK

GO:0008283

cell proliferation

10445845

HgeneLTK

GO:0010666

positive regulation of cardiac muscle cell apoptotic process

10445845

TgeneITGB4

GO:0009611

response to wounding

19403692

TgeneITGB4

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/chr15:41799292/chr17:73746760)
- 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 LTK (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 ITGB4 (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)
ENST00000453182LTKchr1541799292-ENST00000579662ITGB4chr1773746760+3254142017832041008
ENST00000453182LTKchr1541799292-ENST00000339591ITGB4chr1773746760+3626142017833631061
ENST00000453182LTKchr1541799292-ENST00000200181ITGB4chr1773746760+3678142017834141078
ENST00000453182LTKchr1541799292-ENST00000450894ITGB4chr1773746760+3465142017832041008
ENST00000453182LTKchr1541799292-ENST00000449880ITGB4chr1773746760+3627142017833631061

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
ENST00000453182ENST00000579662LTKchr1541799292-ITGB4chr1773746760+0.0047244460.9952755
ENST00000453182ENST00000339591LTKchr1541799292-ITGB4chr1773746760+0.0075857160.9924143
ENST00000453182ENST00000200181LTKchr1541799292-ITGB4chr1773746760+0.0049205120.9950795
ENST00000453182ENST00000450894LTKchr1541799292-ITGB4chr1773746760+0.0044213850.9955786
ENST00000453182ENST00000449880LTKchr1541799292-ITGB4chr1773746760+0.0075989370.992401

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 LTK-ITGB4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LTKchr1541799292ITGB4chr17737467601420414CHRGFPSQCYSAQVKYWIQGDSESEA

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Potential FusionNeoAntigen Information of LTK-ITGB4 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.
LTK-ITGB4_41799292_73746760.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)
LTK-ITGB4chr1541799292chr17737467601420HLA-B57:01YSAQVKYW0.99990.85917
LTK-ITGB4chr1541799292chr17737467601420HLA-B58:02YSAQVKYW0.99940.7116917
LTK-ITGB4chr1541799292chr17737467601420HLA-B58:01YSAQVKYW0.99930.7079917
LTK-ITGB4chr1541799292chr17737467601420HLA-B57:03YSAQVKYW0.99890.8764917
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:25QCYSAQVKY0.94350.6189716
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:02QCYSAQVKY0.92220.6434716
LTK-ITGB4chr1541799292chr17737467601420HLA-B57:01QCYSAQVKYW0.99980.8471717
LTK-ITGB4chr1541799292chr17737467601420HLA-B58:02QCYSAQVKYW0.99910.741717
LTK-ITGB4chr1541799292chr17737467601420HLA-B58:01QCYSAQVKYW0.99730.7728717
LTK-ITGB4chr1541799292chr17737467601420HLA-B57:03QCYSAQVKYW0.99020.856717
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:02SQCYSAQVKY0.94660.5229616
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:21QCYSAQVKY0.93030.6279716
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:05QCYSAQVKY0.84830.6037716
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:31QCYSAQVKY0.7850.6154716
LTK-ITGB4chr1541799292chr17737467601420HLA-C15:04QCYSAQVKY0.44810.7123716
LTK-ITGB4chr1541799292chr17737467601420HLA-B54:01FPSQCYSAQV0.99630.5564414
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:04SQCYSAQVKY0.95580.5276616
LTK-ITGB4chr1541799292chr17737467601420HLA-B57:10YSAQVKYW0.99990.85917
LTK-ITGB4chr1541799292chr17737467601420HLA-B57:04YSAQVKYW0.99970.5946917
LTK-ITGB4chr1541799292chr17737467601420HLA-B58:06YSAQVKYW0.99910.6235917
LTK-ITGB4chr1541799292chr17737467601420HLA-B57:02YSAQVKYW0.99870.7104917
LTK-ITGB4chr1541799292chr17737467601420HLA-B35:11QCYSAQVKY0.92140.6298716
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:20QCYSAQVKY0.85790.6923716
LTK-ITGB4chr1541799292chr17737467601420HLA-B35:28QCYSAQVKY0.82640.703716
LTK-ITGB4chr1541799292chr17737467601420HLA-B35:23QCYSAQVKY0.80420.6808716
LTK-ITGB4chr1541799292chr17737467601420HLA-B35:20QCYSAQVKY0.79430.7293716
LTK-ITGB4chr1541799292chr17737467601420HLA-C15:09QCYSAQVKY0.44810.7123716
LTK-ITGB4chr1541799292chr17737467601420HLA-B18:04QCYSAQVKY0.21970.7467716
LTK-ITGB4chr1541799292chr17737467601420HLA-B57:10QCYSAQVKYW0.99980.8471717
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:135SQCYSAQVKY0.99960.5654616
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:50SQCYSAQVKY0.99950.5094616
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:24SQCYSAQVKY0.9990.5047616
LTK-ITGB4chr1541799292chr17737467601420HLA-B57:04QCYSAQVKYW0.99840.6181717
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:20SQCYSAQVKY0.92450.54616
LTK-ITGB4chr1541799292chr17737467601420HLA-B35:28SQCYSAQVKY0.89580.5613616
LTK-ITGB4chr1541799292chr17737467601420HLA-B35:20SQCYSAQVKY0.79690.5775616
LTK-ITGB4chr1541799292chr17737467601420HLA-B48:02SQCYSAQVKY0.69690.5316616
LTK-ITGB4chr1541799292chr17737467601420HLA-B18:04SQCYSAQVKY0.46680.5738616
LTK-ITGB4chr1541799292chr17737467601420HLA-B15:24SQCYSAQVKYW0.99890.7646617

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Potential FusionNeoAntigen Information of LTK-ITGB4 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.
LTK-ITGB4_41799292_73746760.msa

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)
LTK-ITGB4chr1541799292chr17737467601420DRB1-0401AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0419AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0433AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0435AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0438AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0461AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0463AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0464AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0472AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0475AQVKYWIQGDSESEA1126
LTK-ITGB4chr1541799292chr17737467601420DRB1-0476AQVKYWIQGDSESEA1126

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Fusion breakpoint peptide structures of LTK-ITGB4

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
8912SQCYSAQVKYWIQGLTKITGB4chr1541799292chr17737467601420

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

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-B14:023BVN8912SQCYSAQVKYWIQG-7.9962-8.1096
HLA-B14:023BVN8912SQCYSAQVKYWIQG-5.70842-6.74372
HLA-B52:013W398912SQCYSAQVKYWIQG-6.83737-6.95077
HLA-B52:013W398912SQCYSAQVKYWIQG-4.4836-5.5189
HLA-A11:014UQ28912SQCYSAQVKYWIQG-10.0067-10.1201
HLA-A11:014UQ28912SQCYSAQVKYWIQG-9.03915-10.0745
HLA-A24:025HGA8912SQCYSAQVKYWIQG-6.56204-6.67544
HLA-A24:025HGA8912SQCYSAQVKYWIQG-5.42271-6.45801
HLA-B44:053DX88912SQCYSAQVKYWIQG-7.85648-8.89178
HLA-B44:053DX88912SQCYSAQVKYWIQG-5.3978-5.5112
HLA-A02:016TDR8912SQCYSAQVKYWIQG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LTK-ITGB4

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
LTK-ITGB4chr1541799292chr1773746760414FPSQCYSAQVTTCCCCAGCCAATGTTACTCTGCTCAGGTA
LTK-ITGB4chr1541799292chr1773746760616SQCYSAQVKYAGCCAATGTTACTCTGCTCAGGTAAAGTAC
LTK-ITGB4chr1541799292chr1773746760617SQCYSAQVKYWAGCCAATGTTACTCTGCTCAGGTAAAGTACTGG
LTK-ITGB4chr1541799292chr1773746760716QCYSAQVKYCAATGTTACTCTGCTCAGGTAAAGTAC
LTK-ITGB4chr1541799292chr1773746760717QCYSAQVKYWCAATGTTACTCTGCTCAGGTAAAGTACTGG
LTK-ITGB4chr1541799292chr1773746760917YSAQVKYWTACTCTGCTCAGGTAAAGTACTGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LTK-ITGB4chr1541799292chr17737467601126AQVKYWIQGDSESEAGCTCAGGTAAAGTACTGGATTCAGGGTGACTCCGAATCCGAAGCC

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Information of the samples that have these potential fusion neoantigens of LTK-ITGB4

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
Non-CancerLTK-ITGB4chr1541799292ENST00000453182chr1773746760ENST00000200181161N

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

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
HgeneLTKchr15:41799292chr17:73746760ENST00000263800-1120425_449513865.0TransmembraneHelical
HgeneLTKchr15:41799292chr17:73746760ENST00000355166-1019425_449452804.0TransmembraneHelical

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

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Related Drugs to LTK-ITGB4

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 LTK-ITGB4

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