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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:SKIV2L2-IGF2R

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SKIV2L2-IGF2R
FusionPDB ID: 82111
FusionGDB2.0 ID: 82111
HgeneTgene
Gene symbol

SKIV2L2

IGF2R

Gene ID

23517

3482

Gene nameMtr4 exosome RNA helicaseinsulin like growth factor 2 receptor
SynonymsDob1|KIAA0052|Mtr4|SKIV2L2|fSAP118CD222|CI-M6PR|CIMPR|M6P-R|M6P/IGF2R|MPR 300|MPR1|MPR300|MPRI
Cytomap

5q11.2

6q25.3

Type of geneprotein-codingprotein-coding
Descriptionexosome RNA helicase MTR4ATP-dependent RNA helicase DOB1ATP-dependent RNA helicase SKIV2L2ATP-dependent helicase SKIV2L2Ski2 like RNA helicase 2TRAMP-like complex helicasefunctional spliceosome-associated protein 118superkiller viralicidic activitycation-independent mannose-6-phosphate receptor300 kDa mannose 6-phosphate receptorCI Man-6-P receptorIGF-II receptorM6P/IGF2 receptorinsulin-like growth factor II receptor
Modification date2020031320200315
UniProtAcc.

P11717

Main function of 5'-partner protein: FUNCTION: Mediates the transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes (PubMed:2963003, PubMed:18817523). Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex (PubMed:2963003, PubMed:18817523). The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer (PubMed:18817523). This receptor also binds IGF2 (PubMed:18046459). Acts as a positive regulator of T-cell coactivation by binding DPP4 (PubMed:10900005). {ECO:0000269|PubMed:10900005, ECO:0000269|PubMed:18046459, ECO:0000269|PubMed:18817523, ECO:0000269|PubMed:2963003}.
Ensembl transtripts involved in fusion geneENST idsENST00000504388, ENST00000230640, 
ENST00000545714, 
ENST00000356956, 
ENST00000475584, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 12 X 8=32643 X 3 X 3=27
# samples 153
** MAII scorelog2(15/3264*10)=-4.44360665147561
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: SKIV2L2 [Title/Abstract] AND IGF2R [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SKIV2L2 [Title/Abstract] AND IGF2R [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SKIV2L2(54603975)-IGF2R(160412216), # samples:2
Anticipated loss of major functional domain due to fusion event.SKIV2L2-IGF2R 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.
SKIV2L2-IGF2R 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.
SKIV2L2-IGF2R 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.
SKIV2L2-IGF2R 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.
SKIV2L2-IGF2R seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
SKIV2L2-IGF2R 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
HgeneSKIV2L2

GO:0006401

RNA catabolic process

29906447



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/chr5:54603975/chr6:160412216)
- 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 SKIV2L2 (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 IGF2R (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)
ENST00000230640SKIV2L2chr554603975+ENST00000356956IGF2Rchr6160412216+918238823377142493

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
ENST00000230640ENST00000356956SKIV2L2chr554603975+IGF2Rchr6160412216+0.0003104430.9996896

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 SKIV2L2-IGF2R

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SKIV2L2chr554603975IGF2Rchr616041221638852KWKGPPGSADKAGYTWEAVDTKNNVL

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Potential FusionNeoAntigen Information of SKIV2L2-IGF2R 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.
SKIV2L2-IGF2R_54603975_160412216.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)
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B58:01SADKAGYTW0.99650.9497716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:01SADKAGYTW0.99380.9673716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B58:02SADKAGYTW0.98890.9158716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B15:17SADKAGYTW0.98030.9343716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B53:01SADKAGYTW0.95540.5793716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B39:06DKAGYTWEA0.95240.9652918
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B15:16SADKAGYTW0.90450.9307716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:03SADKAGYTW0.88910.9832716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B35:08SADKAGYTW0.84450.8126716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-A31:08SADKAGYTW0.81190.5988716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-A32:13SADKAGYTW0.75290.9599716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:01GSADKAGYTW0.99970.9393616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B58:02GSADKAGYTW0.99940.8698616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B58:01GSADKAGYTW0.99940.912616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B15:17GSADKAGYTW0.99790.8676616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:03GSADKAGYTW0.99360.9753616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B15:16GSADKAGYTW0.98690.8817616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-A32:13GSADKAGYTW0.91830.9523616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C04:10SADKAGYTW0.99460.9324716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C04:07SADKAGYTW0.99410.9303716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C05:09SADKAGYTW0.9930.9491716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C08:15SADKAGYTW0.95550.9764716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B73:01DKAGYTWEA0.50610.9497918
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B44:08SADKAGYTW0.4180.7078716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C08:03SADKAGYTW0.0070.9836716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-A11:01GYTWEAVDTK0.63780.53041222
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-A11:01AGYTWEAVDTK0.99810.55061122
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B44:21ADKAGYTW0.99290.5696816
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:04SADKAGYTW0.99520.7485716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C04:01SADKAGYTW0.99410.9303716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:10SADKAGYTW0.99380.9673716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C04:03SADKAGYTW0.99310.9327716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C05:01SADKAGYTW0.9930.9491716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:02SADKAGYTW0.97840.9548716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B58:06SADKAGYTW0.97690.9256716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C08:02SADKAGYTW0.95550.9764716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B53:02SADKAGYTW0.89920.5273716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B15:13SADKAGYTW0.88890.8907716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-A32:01SADKAGYTW0.78230.9408716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B15:24SADKAGYTW0.12590.95716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B51:06SADKAGYTW0.11860.6535716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-C08:01SADKAGYTW0.0070.9836716
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:04GSADKAGYTW0.99980.7045616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:10GSADKAGYTW0.99970.9393616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B58:06GSADKAGYTW0.99930.8739616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-B57:02GSADKAGYTW0.99670.9472616
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-A11:02GYTWEAVDTK0.63780.53041222
SKIV2L2-IGF2Rchr554603975chr6160412216388HLA-A11:02AGYTWEAVDTK0.99810.55061122

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Potential FusionNeoAntigen Information of SKIV2L2-IGF2R 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 SKIV2L2-IGF2R

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
3105GSADKAGYTWEAVDSKIV2L2IGF2Rchr554603975chr6160412216388

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SKIV2L2-IGF2R

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-B14:023BVN3105GSADKAGYTWEAVD-7.9962-8.1096
HLA-B14:023BVN3105GSADKAGYTWEAVD-5.70842-6.74372
HLA-B52:013W393105GSADKAGYTWEAVD-6.83737-6.95077
HLA-B52:013W393105GSADKAGYTWEAVD-4.4836-5.5189
HLA-A11:014UQ23105GSADKAGYTWEAVD-10.0067-10.1201
HLA-A11:014UQ23105GSADKAGYTWEAVD-9.03915-10.0745
HLA-A24:025HGA3105GSADKAGYTWEAVD-6.56204-6.67544
HLA-A24:025HGA3105GSADKAGYTWEAVD-5.42271-6.45801
HLA-B44:053DX83105GSADKAGYTWEAVD-7.85648-8.89178
HLA-B44:053DX83105GSADKAGYTWEAVD-5.3978-5.5112
HLA-A02:016TDR3105GSADKAGYTWEAVD-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SKIV2L2-IGF2R

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
SKIV2L2-IGF2Rchr554603975chr61604122161122AGYTWEAVDTKGGCAGGTTATACATGGGAAGCTGTTGATACCAA
SKIV2L2-IGF2Rchr554603975chr61604122161222GYTWEAVDTKAGGTTATACATGGGAAGCTGTTGATACCAA
SKIV2L2-IGF2Rchr554603975chr6160412216616GSADKAGYTWAGGGTCTGCAGACAAGGCAGGTTATACATG
SKIV2L2-IGF2Rchr554603975chr6160412216716SADKAGYTWGTCTGCAGACAAGGCAGGTTATACATG
SKIV2L2-IGF2Rchr554603975chr6160412216816ADKAGYTWTGCAGACAAGGCAGGTTATACATG
SKIV2L2-IGF2Rchr554603975chr6160412216918DKAGYTWEAAGACAAGGCAGGTTATACATGGGAAGC

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 SKIV2L2-IGF2R

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
GBMSKIV2L2-IGF2Rchr554603975ENST00000230640chr6160412216ENST00000356956TCGA-02-2486-01A

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Potential target of CAR-T therapy development for SKIV2L2-IGF2R

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
TgeneIGF2Rchr5:54603975chr6:160412216ENST000003569560482305_232702492.0TransmembraneHelical

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 SKIV2L2-IGF2R

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 SKIV2L2-IGF2R

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