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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:STK39-ITGB6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: STK39-ITGB6
FusionPDB ID: 87556
FusionGDB2.0 ID: 87556
HgeneTgene
Gene symbol

STK39

ITGB6

Gene ID

27347

3694

Gene nameserine/threonine kinase 39integrin subunit beta 6
SynonymsDCHT|PASK|SPAKAI1H
Cytomap

2q24.3

2q24.2

Type of geneprotein-codingprotein-coding
DescriptionSTE20/SPS1-related proline-alanine-rich protein kinaseSTE20/SPS1 homologSte20-like protein kinaseproline-alanine-rich STE20-related kinaseserine threonine kinase 39 (STE20/SPS1 homolog, yeast)serine/threonine-protein kinase 39small intestine SPAK-liintegrin beta-6integrin, beta 6
Modification date2020031320200313
UniProtAcc.

P18564

Main function of 5'-partner protein: FUNCTION: Integrin alpha-V:beta-6 (ITGAV:ITGB6) is a receptor for fibronectin and cytotactin (PubMed:17545607, PubMed:17158881). It recognizes the sequence R-G-D in its ligands (PubMed:17545607, PubMed:17158881). Internalisation of integrin alpha-V/beta-6 via clathrin-mediated endocytosis promotes carcinoma cell invasion (PubMed:17545607, PubMed:17158881). ITGAV:ITGB6 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:17158881). Integrin alpha-V:beta-6 (ITGAV:ITGB6) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (PubMed:15184403, PubMed:22278742, PubMed:28117447). {ECO:0000269|PubMed:15184403, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:17545607, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:28117447}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for Coxsackievirus A9 and Coxsackievirus B1. {ECO:0000269|PubMed:15194773, ECO:0000269|PubMed:9426447}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for Herpes simplex virus-1/HHV-1 (PubMed:24367260). {ECO:0000269|PubMed:24367260}.
Ensembl transtripts involved in fusion geneENST idsENST00000355999, ENST00000487143, 
ENST00000409872, ENST00000409967, 
ENST00000428609, ENST00000485635, 
ENST00000283249, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 9 X 9=9728 X 6 X 8=384
# samples 1210
** MAII scorelog2(12/972*10)=-3.01792190799726
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/384*10)=-1.94110631094643
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: STK39 [Title/Abstract] AND ITGB6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: STK39 [Title/Abstract] AND ITGB6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)STK39(168921829)-ITGB6(160994710), # samples:3
Anticipated loss of major functional domain due to fusion event.STK39-ITGB6 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.
STK39-ITGB6 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.
STK39-ITGB6 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.
STK39-ITGB6 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
HgeneSTK39

GO:0018105

peptidyl-serine phosphorylation

24393035

HgeneSTK39

GO:0018107

peptidyl-threonine phosphorylation

24393035

HgeneSTK39

GO:0023014

signal transduction by protein phosphorylation

24393035

HgeneSTK39

GO:0035556

intracellular signal transduction

24393035

HgeneSTK39

GO:1901017

negative regulation of potassium ion transmembrane transporter activity

24393035

HgeneSTK39

GO:1901380

negative regulation of potassium ion transmembrane transport

24393035

HgeneSTK39

GO:1905408

negative regulation of creatine transmembrane transporter activity

25531585

HgeneSTK39

GO:2000650

negative regulation of sodium ion transmembrane transporter activity

25531585

TgeneITGB6

GO:0033627

cell adhesion mediated by integrin

17158881

TgeneITGB6

GO:1901388

regulation of transforming growth factor beta activation

22278742



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/chr2:168921829/chr2:160994710)
- 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 STK39 (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 ITGB6 (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)
ENST00000355999STK39chr2168921829-ENST00000283249ITGB6chr2160994710-534120114543270938

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
ENST00000355999ENST00000283249STK39chr2168921829-ITGB6chr2160994710-0.0003367590.99966323

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 STK39-ITGB6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
STK39chr2168921829ITGB6chr21609947102011519PEQIQSLSVHDSQELRSEVELEVLGD

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Potential FusionNeoAntigen Information of STK39-ITGB6 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.
STK39-ITGB6_168921829_160994710.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)
STK39-ITGB6chr2168921829chr21609947102011HLA-B13:01QELRSEVEL0.99390.92861221
STK39-ITGB6chr2168921829chr21609947102011HLA-B44:03QELRSEVEL0.98980.96431221
STK39-ITGB6chr2168921829chr21609947102011HLA-B45:01QELRSEVEL0.96620.90691221
STK39-ITGB6chr2168921829chr21609947102011HLA-B18:01QELRSEVEL0.86570.88431221
STK39-ITGB6chr2168921829chr21609947102011HLA-B39:13QELRSEVEL0.82010.92451221
STK39-ITGB6chr2168921829chr21609947102011HLA-B41:01QELRSEVEL0.76350.9791221
STK39-ITGB6chr2168921829chr21609947102011HLA-B39:13SQELRSEVEL0.91650.87931121
STK39-ITGB6chr2168921829chr21609947102011HLA-C03:07LSVHDSQEL0.99960.9456615
STK39-ITGB6chr2168921829chr21609947102011HLA-C03:19LSVHDSQEL0.99960.9805615
STK39-ITGB6chr2168921829chr21609947102011HLA-B40:06QELRSEVEL0.99950.61851221
STK39-ITGB6chr2168921829chr21609947102011HLA-C03:08LSVHDSQEL0.99950.8889615
STK39-ITGB6chr2168921829chr21609947102011HLA-B51:07DSQELRSEV0.99840.74731019
STK39-ITGB6chr2168921829chr21609947102011HLA-B44:10QELRSEVEL0.99810.50741221
STK39-ITGB6chr2168921829chr21609947102011HLA-C08:13LSVHDSQEL0.98310.8659615
STK39-ITGB6chr2168921829chr21609947102011HLA-C08:04LSVHDSQEL0.98310.8659615
STK39-ITGB6chr2168921829chr21609947102011HLA-C08:03LSVHDSQEL0.87520.9407615
STK39-ITGB6chr2168921829chr21609947102011HLA-B39:08QELRSEVEL0.84250.90131221
STK39-ITGB6chr2168921829chr21609947102011HLA-B39:08SQELRSEVEL0.95380.74221121
STK39-ITGB6chr2168921829chr21609947102011HLA-C03:03LSVHDSQEL0.99960.9783615
STK39-ITGB6chr2168921829chr21609947102011HLA-C03:04LSVHDSQEL0.99960.9783615
STK39-ITGB6chr2168921829chr21609947102011HLA-B40:04QELRSEVEL0.99940.7341221
STK39-ITGB6chr2168921829chr21609947102011HLA-C03:17LSVHDSQEL0.99930.942615
STK39-ITGB6chr2168921829chr21609947102011HLA-C03:05LSVHDSQEL0.99920.8754615
STK39-ITGB6chr2168921829chr21609947102011HLA-C03:06LSVHDSQEL0.99020.9757615
STK39-ITGB6chr2168921829chr21609947102011HLA-B44:07QELRSEVEL0.98980.96431221
STK39-ITGB6chr2168921829chr21609947102011HLA-B44:26QELRSEVEL0.98980.96431221
STK39-ITGB6chr2168921829chr21609947102011HLA-B44:13QELRSEVEL0.98980.96431221
STK39-ITGB6chr2168921829chr21609947102011HLA-B41:03QELRSEVEL0.91210.75441221
STK39-ITGB6chr2168921829chr21609947102011HLA-C08:01LSVHDSQEL0.87520.9407615
STK39-ITGB6chr2168921829chr21609947102011HLA-B18:05QELRSEVEL0.86570.88431221
STK39-ITGB6chr2168921829chr21609947102011HLA-B18:11QELRSEVEL0.84440.87631221
STK39-ITGB6chr2168921829chr21609947102011HLA-B39:02QELRSEVEL0.82990.92941221
STK39-ITGB6chr2168921829chr21609947102011HLA-B39:31QELRSEVEL0.82280.92851221
STK39-ITGB6chr2168921829chr21609947102011HLA-B39:11QELRSEVEL0.79160.93241221
STK39-ITGB6chr2168921829chr21609947102011HLA-B35:13LSVHDSQEL0.7810.9068615
STK39-ITGB6chr2168921829chr21609947102011HLA-B40:04SQELRSEVEL0.9640.7041121
STK39-ITGB6chr2168921829chr21609947102011HLA-B39:11VHDSQELRSEV0.99210.7964819

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Potential FusionNeoAntigen Information of STK39-ITGB6 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.
STK39-ITGB6_168921829_160994710.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)
STK39-ITGB6chr2168921829chr21609947102011DRB1-0415PEQIQSLSVHDSQEL015
STK39-ITGB6chr2168921829chr21609947102011DRB1-0436PEQIQSLSVHDSQEL015
STK39-ITGB6chr2168921829chr21609947102011DRB1-0453PEQIQSLSVHDSQEL015
STK39-ITGB6chr2168921829chr21609947102011DRB1-0458PEQIQSLSVHDSQEL015
STK39-ITGB6chr2168921829chr21609947102011DRB1-1002PEQIQSLSVHDSQEL015
STK39-ITGB6chr2168921829chr21609947102011DRB1-1503SQELRSEVELEVLGD1126
STK39-ITGB6chr2168921829chr21609947102011DRB1-1523SQELRSEVELEVLGD1126

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Fusion breakpoint peptide structures of STK39-ITGB6

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
5677LSVHDSQELRSEVESTK39ITGB6chr2168921829chr21609947102011

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of STK39-ITGB6

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-B14:023BVN5677LSVHDSQELRSEVE-7.15543-7.26883
HLA-B14:023BVN5677LSVHDSQELRSEVE-4.77435-5.80965
HLA-B52:013W395677LSVHDSQELRSEVE-6.80875-6.92215
HLA-B52:013W395677LSVHDSQELRSEVE-4.20386-5.23916
HLA-A11:014UQ25677LSVHDSQELRSEVE-7.5194-8.5547
HLA-A11:014UQ25677LSVHDSQELRSEVE-6.9601-7.0735
HLA-A24:025HGA5677LSVHDSQELRSEVE-7.52403-7.63743
HLA-A24:025HGA5677LSVHDSQELRSEVE-5.82433-6.85963
HLA-B27:056PYJ5677LSVHDSQELRSEVE-3.28285-4.31815
HLA-B44:053DX85677LSVHDSQELRSEVE-5.91172-6.94702
HLA-B44:053DX85677LSVHDSQELRSEVE-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of STK39-ITGB6

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
STK39-ITGB6chr2168921829chr21609947101019DSQELRSEVGACTCTCAGGAACTGCGGTCTGAGGTG
STK39-ITGB6chr2168921829chr21609947101121SQELRSEVELTCTCAGGAACTGCGGTCTGAGGTGGAACTG
STK39-ITGB6chr2168921829chr21609947101221QELRSEVELCAGGAACTGCGGTCTGAGGTGGAACTG
STK39-ITGB6chr2168921829chr2160994710615LSVHDSQELCTCTCTGTGCACGACTCTCAGGAACTG
STK39-ITGB6chr2168921829chr2160994710819VHDSQELRSEVGTGCACGACTCTCAGGAACTGCGGTCTGAGGTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
STK39-ITGB6chr2168921829chr2160994710015PEQIQSLSVHDSQELCCCGAACAAATACAGTCCCTCTCTGTGCACGACTCTCAGGAACTG
STK39-ITGB6chr2168921829chr21609947101126SQELRSEVELEVLGDTCTCAGGAACTGCGGTCTGAGGTGGAACTGGAAGTATTAGGAGAC

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Information of the samples that have these potential fusion neoantigens of STK39-ITGB6

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
BRCASTK39-ITGB6chr2168921829ENST00000355999chr2160994710ENST00000283249TCGA-E2-A14Z-01A

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Potential target of CAR-T therapy development for STK39-ITGB6

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
TgeneITGB6chr2:168921829chr2:160994710ENST00000283249715710_7300789.0TransmembraneHelical
TgeneITGB6chr2:168921829chr2:160994710ENST00000409872816710_7300789.0TransmembraneHelical

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 STK39-ITGB6

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 STK39-ITGB6

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