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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:SKAP1-IKZF3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SKAP1-IKZF3
FusionPDB ID: 82057
FusionGDB2.0 ID: 82057
HgeneTgene
Gene symbol

SKAP1

IKZF3

Gene ID

8631

22806

Gene namesrc kinase associated phosphoprotein 1IKAROS family zinc finger 3
SynonymsHEL-S-81p|SCAP1|SKAP55AIO|AIOLOS|ZNFN1A3
Cytomap

17q21.32

17q12-q21.1

Type of geneprotein-codingprotein-coding
Descriptionsrc kinase-associated phosphoprotein 1SKAP-55epididymis secretory sperm binding protein Li 81ppp55src family-associated phosphoprotein 1src kinase-associated phosphoprotein of 55 kDazinc finger protein Aioloszinc finger DNA binding protein Aioloszinc finger protein, subfamily 1A, 3 (Aiolos)
Modification date2020031320200327
UniProtAcc.

Q9UKT9

Main function of 5'-partner protein: FUNCTION: Transcription factor that plays an important role in the regulation of lymphocyte differentiation. Plays an essential role in regulation of B-cell differentiation, proliferation and maturation to an effector state. Involved in regulating BCL2 expression and controlling apoptosis in T-cells in an IL2-dependent manner. {ECO:0000269|PubMed:10369681}.
Ensembl transtripts involved in fusion geneENST idsENST00000336915, ENST00000584924, 
ENST00000346243, ENST00000350532, 
ENST00000351680, ENST00000439016, 
ENST00000467757, ENST00000583368, 
ENST00000346872, ENST00000377944, 
ENST00000377945, ENST00000377952, 
ENST00000377958, ENST00000394189, 
ENST00000439167, ENST00000535189, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score26 X 10 X 10=260034 X 12 X 14=5712
# samples 3549
** MAII scorelog2(35/2600*10)=-2.89308479608349
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(49/5712*10)=-3.54314232502653
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SKAP1 [Title/Abstract] AND IKZF3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SKAP1 [Title/Abstract] AND IKZF3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SKAP1(46423267)-IKZF3(37922746), # samples:3
Anticipated loss of major functional domain due to fusion event.SKAP1-IKZF3 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.
SKAP1-IKZF3 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.
SKAP1-IKZF3 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.
SKAP1-IKZF3 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.
SKAP1-IKZF3 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
SKAP1-IKZF3 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
SKAP1-IKZF3 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
SKAP1-IKZF3 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
SKAP1-IKZF3 seems lost the major protein functional domain in Tgene 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
HgeneSKAP1

GO:0002821

positive regulation of adaptive immune response

12652296

HgeneSKAP1

GO:0033625

positive regulation of integrin activation

12652296

HgeneSKAP1

GO:0034116

positive regulation of heterotypic cell-cell adhesion

12652296

HgeneSKAP1

GO:0045944

positive regulation of transcription by RNA polymerase II

11909961

HgeneSKAP1

GO:1903039

positive regulation of leukocyte cell-cell adhesion

12652296



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/chr17:46423267/chr17:37922746)
- 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 SKAP1 (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 IKZF3 (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)
ENST00000336915SKAP1chr1746423267-ENST00000346872IKZF3chr1737922746-1899350701053327
ENST00000336915SKAP1chr1746423267-ENST00000394189IKZF3chr1737922746-1560350701053327
ENST00000336915SKAP1chr1746423267-ENST00000439167IKZF3chr1737922746-1560350701053327
ENST00000336915SKAP1chr1746423267-ENST00000535189IKZF3chr1737922746-1560350701053327
ENST00000336915SKAP1chr1746423267-ENST00000377944IKZF3chr1737922746-1560350701053327
ENST00000336915SKAP1chr1746423267-ENST00000377945IKZF3chr1737922746-1560350701053327
ENST00000336915SKAP1chr1746423267-ENST00000377952IKZF3chr1737922746-1560350701053327
ENST00000336915SKAP1chr1746423267-ENST00000377958IKZF3chr1737922746-1560350701053327
ENST00000584924SKAP1chr1746423267-ENST00000346872IKZF3chr1737922746-1928379991082327
ENST00000584924SKAP1chr1746423267-ENST00000394189IKZF3chr1737922746-1589379991082327
ENST00000584924SKAP1chr1746423267-ENST00000439167IKZF3chr1737922746-1589379991082327
ENST00000584924SKAP1chr1746423267-ENST00000535189IKZF3chr1737922746-1589379991082327
ENST00000584924SKAP1chr1746423267-ENST00000377944IKZF3chr1737922746-1589379991082327
ENST00000584924SKAP1chr1746423267-ENST00000377945IKZF3chr1737922746-1589379991082327
ENST00000584924SKAP1chr1746423267-ENST00000377952IKZF3chr1737922746-1589379991082327
ENST00000584924SKAP1chr1746423267-ENST00000377958IKZF3chr1737922746-1589379991082327

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
ENST00000336915ENST00000346872SKAP1chr1746423267-IKZF3chr1737922746-0.0009214850.9990785
ENST00000336915ENST00000394189SKAP1chr1746423267-IKZF3chr1737922746-0.0011688470.9988312
ENST00000336915ENST00000439167SKAP1chr1746423267-IKZF3chr1737922746-0.0011688470.9988312
ENST00000336915ENST00000535189SKAP1chr1746423267-IKZF3chr1737922746-0.0011688470.9988312
ENST00000336915ENST00000377944SKAP1chr1746423267-IKZF3chr1737922746-0.0011688470.9988312
ENST00000336915ENST00000377945SKAP1chr1746423267-IKZF3chr1737922746-0.0011688470.9988312
ENST00000336915ENST00000377952SKAP1chr1746423267-IKZF3chr1737922746-0.0011688470.9988312
ENST00000336915ENST00000377958SKAP1chr1746423267-IKZF3chr1737922746-0.0011688470.9988312
ENST00000584924ENST00000346872SKAP1chr1746423267-IKZF3chr1737922746-0.0009396650.99906033
ENST00000584924ENST00000394189SKAP1chr1746423267-IKZF3chr1737922746-0.0011906430.99880934
ENST00000584924ENST00000439167SKAP1chr1746423267-IKZF3chr1737922746-0.0011906430.99880934
ENST00000584924ENST00000535189SKAP1chr1746423267-IKZF3chr1737922746-0.0011906430.99880934
ENST00000584924ENST00000377944SKAP1chr1746423267-IKZF3chr1737922746-0.0011906430.99880934
ENST00000584924ENST00000377945SKAP1chr1746423267-IKZF3chr1737922746-0.0011906430.99880934
ENST00000584924ENST00000377952SKAP1chr1746423267-IKZF3chr1737922746-0.0011906430.99880934
ENST00000584924ENST00000377958SKAP1chr1746423267-IKZF3chr1737922746-0.0011906430.99880934

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 SKAP1-IKZF3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SKAP1chr1746423267IKZF3chr173792274635093TSDAPFLSDYQDEGEKRHCFDVNYNS
SKAP1chr1746423267IKZF3chr173792274637993TSDAPFLSDYQDEGEKRHCFDVNYNS

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Potential FusionNeoAntigen Information of SKAP1-IKZF3 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.
SKAP1-IKZF3_46423267_37922746.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)
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B18:01DEGEKRHCF0.98960.90751120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B44:03DEGEKRHCF0.98370.90681120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B13:01YQDEGEKRHCF0.98090.9825920
SKAP1-IKZF3chr1746423267chr1737922746350HLA-C05:09YQDEGEKRHCF10.9722920
SKAP1-IKZF3chr1746423267chr1737922746350HLA-C08:15YQDEGEKRHCF10.9831920
SKAP1-IKZF3chr1746423267chr1737922746350HLA-C04:10YQDEGEKRHCF10.7854920
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B39:08YQDEGEKRHCF0.99520.9342920
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B18:04DEGEKRHCF0.99210.9251120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B18:07DEGEKRHCF0.99050.85251120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B18:08DEGEKRHCF0.99030.72521120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B18:05DEGEKRHCF0.98960.90751120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B18:06DEGEKRHCF0.98950.92821120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B18:03DEGEKRHCF0.9860.90161120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B44:07DEGEKRHCF0.98370.90681120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B44:26DEGEKRHCF0.98370.90681120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B44:13DEGEKRHCF0.98370.90681120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-B18:11DEGEKRHCF0.81230.89451120
SKAP1-IKZF3chr1746423267chr1737922746350HLA-C05:01YQDEGEKRHCF10.9722920
SKAP1-IKZF3chr1746423267chr1737922746350HLA-C08:02YQDEGEKRHCF10.9831920

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Potential FusionNeoAntigen Information of SKAP1-IKZF3 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 SKAP1-IKZF3

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
5606LSDYQDEGEKRHCFSKAP1IKZF3chr1746423267chr1737922746350

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SKAP1-IKZF3

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-B14:023BVN5606LSDYQDEGEKRHCF-7.9962-8.1096
HLA-B14:023BVN5606LSDYQDEGEKRHCF-5.70842-6.74372
HLA-B52:013W395606LSDYQDEGEKRHCF-6.83737-6.95077
HLA-B52:013W395606LSDYQDEGEKRHCF-4.4836-5.5189
HLA-A11:014UQ25606LSDYQDEGEKRHCF-10.0067-10.1201
HLA-A11:014UQ25606LSDYQDEGEKRHCF-9.03915-10.0745
HLA-A24:025HGA5606LSDYQDEGEKRHCF-6.56204-6.67544
HLA-A24:025HGA5606LSDYQDEGEKRHCF-5.42271-6.45801
HLA-B44:053DX85606LSDYQDEGEKRHCF-7.85648-8.89178
HLA-B44:053DX85606LSDYQDEGEKRHCF-5.3978-5.5112
HLA-A02:016TDR5606LSDYQDEGEKRHCF-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SKAP1-IKZF3

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
SKAP1-IKZF3chr1746423267chr17379227461120DEGEKRHCFATGAGGGTGAGAAGCGCCACTGCTTTG
SKAP1-IKZF3chr1746423267chr1737922746920YQDEGEKRHCFATCAGGATGAGGGTGAGAAGCGCCACTGCTTTG

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 SKAP1-IKZF3

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
BRCASKAP1-IKZF3chr1746423267ENST00000336915chr1737922746ENST00000346872TCGA-AR-A24U-01A

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Potential target of CAR-T therapy development for SKAP1-IKZF3

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 SKAP1-IKZF3

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 SKAP1-IKZF3

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