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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:IGFBP2-XRCC5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: IGFBP2-XRCC5
FusionPDB ID: 38569
FusionGDB2.0 ID: 38569
HgeneTgene
Gene symbol

IGFBP2

XRCC5

Gene ID

3485

7520

Gene nameinsulin like growth factor binding protein 2X-ray repair cross complementing 5
SynonymsIBP2|IGF-BP53KARP-1|KARP1|KU80|KUB2|Ku86|NFIV
Cytomap

2q35

2q35

Type of geneprotein-codingprotein-coding
Descriptioninsulin-like growth factor-binding protein 2IGF-binding protein 2insulin-like growth factor binding protein 2, 36kDaX-ray repair cross-complementing protein 586 kDa subunit of Ku antigenATP-dependent DNA helicase 2 subunit 2ATP-dependent DNA helicase II 80 kDa subunitCTC box-binding factor 85 kDa subunitCTC85CTCBFDNA repair protein XRCC5Ku autoantigen, 80kDaKu
Modification date2020031320200313
UniProtAcc

P18065

Main function of 5'-partner protein: FUNCTION: Inhibits IGF-mediated growth and developmental rates. IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. {ECO:0000269|PubMed:19081843}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000233809, ENST00000456764, 
ENST00000471649, ENST00000392132, 
ENST00000392133, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 5 X 4=1409 X 6 X 5=270
# samples 710
** MAII scorelog2(7/140*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/270*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: IGFBP2 [Title/Abstract] AND XRCC5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: IGFBP2 [Title/Abstract] AND XRCC5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)IGFBP2(217498688)-XRCC5(217054947), # samples:1
Anticipated loss of major functional domain due to fusion event.IGFBP2-XRCC5 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.
IGFBP2-XRCC5 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.
IGFBP2-XRCC5 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.
IGFBP2-XRCC5 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
HgeneIGFBP2

GO:0042104

positive regulation of activated T cell proliferation

15694994

TgeneXRCC5

GO:0002218

activation of innate immune response

28712728

TgeneXRCC5

GO:0006303

double-strand break repair via nonhomologous end joining

26359349

TgeneXRCC5

GO:0045860

positive regulation of protein kinase activity

22504299

TgeneXRCC5

GO:0071480

cellular response to gamma radiation

26359349



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/chr2:217498688/chr2:217054947)
- 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 IGFBP2 (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 XRCC5 (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)
ENST00000233809IGFBP2chr2217498688+ENST00000392133XRCC5chr2217054947+2037571114935273
ENST00000233809IGFBP2chr2217498688+ENST00000392132XRCC5chr2217054947+2025571114935273

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
ENST00000233809ENST00000392133IGFBP2chr2217498688+XRCC5chr2217054947+0.0022279940.9977719
ENST00000233809ENST00000392132IGFBP2chr2217498688+XRCC5chr2217054947+0.0021457840.9978542

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 IGFBP2-XRCC5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
IGFBP2chr2217498688XRCC5chr2217054947571150KRRDAEYGASPEQVAASNQLINHIEQ

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Potential FusionNeoAntigen Information of IGFBP2-XRCC5 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.
IGFBP2-XRCC5_217498688_217054947.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)
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B39:01EQVAASNQL0.98370.87031120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B39:13EQVAASNQL0.97650.91511120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B38:02EQVAASNQL0.96670.94581120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B38:01EQVAASNQL0.95720.93121120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B15:10EQVAASNQL0.86020.53311120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B15:37EQVAASNQL0.68960.63821120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B13:01EQVAASNQL0.67910.93471120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B40:02AEYGASPEQV0.99930.506414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B45:01AEYGASPEQV0.99740.9839414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B50:02AEYGASPEQV0.99720.8482414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B40:01AEYGASPEQV0.99050.7837414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B40:05AEYGASPEQV0.94090.6546414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B44:05AEYGASPEQV0.92420.7366414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B50:01AEYGASPEQV0.86750.9649414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B41:01AEYGASPEQV0.8460.958414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B41:02AEYGASPEQV0.84180.5632414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B45:01AEYGASPEQVA0.99960.9928415
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B50:02AEYGASPEQVA0.99960.9541415
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B41:01AEYGASPEQVA0.99630.9769415
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B50:01AEYGASPEQVA0.99520.9787415
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B35:03SPEQVAASNQL0.94850.6378920
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B35:04SPEQVAASNQL0.88950.8536920
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B35:02SPEQVAASNQL0.88950.8536920
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B39:09EQVAASNQL0.98710.67931120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B39:05EQVAASNQL0.97380.85371120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B39:08EQVAASNQL0.91240.7781120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B40:06AEYGASPEQV0.99920.8821414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B44:10AEYGASPEQV0.98640.9488414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B40:06AEYGASPEQVA0.99980.9525415
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B35:12SPEQVAASNQL0.88950.8536920
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B39:10SPEQVAASNQL0.84110.8278920
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B39:02EQVAASNQL0.98530.91041120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B39:31EQVAASNQL0.98390.87151120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B38:05EQVAASNQL0.95720.93121120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B39:11EQVAASNQL0.90090.75071120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B15:73EQVAASNQL0.74930.90161120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B15:09EQVAASNQL0.69510.68081120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B15:30EQVAASNQL0.66510.81691120
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B40:40AEYGASPEQV0.99850.5465414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B40:04AEYGASPEQV0.99570.9608414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B40:36AEYGASPEQV0.9910.775414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B40:49AEYGASPEQV0.98810.7985414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B50:04AEYGASPEQV0.86750.9649414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B50:05AEYGASPEQV0.86750.9649414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B41:03AEYGASPEQV0.78180.9116414
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B50:05AEYGASPEQVA0.99520.9787415
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B50:04AEYGASPEQVA0.99520.9787415
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B15:73SPEQVAASNQL0.9650.8611920
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B35:09SPEQVAASNQL0.88950.8536920
IGFBP2-XRCC5chr2217498688chr2217054947571HLA-B67:01SPEQVAASNQL0.83640.7556920

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Potential FusionNeoAntigen Information of IGFBP2-XRCC5 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.
IGFBP2-XRCC5_217498688_217054947.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)
IGFBP2-XRCC5chr2217498688chr2217054947571DRB1-0901DAEYGASPEQVAASN318
IGFBP2-XRCC5chr2217498688chr2217054947571DRB1-0901RDAEYGASPEQVAAS217
IGFBP2-XRCC5chr2217498688chr2217054947571DRB1-0903DAEYGASPEQVAASN318
IGFBP2-XRCC5chr2217498688chr2217054947571DRB1-0908DAEYGASPEQVAASN318
IGFBP2-XRCC5chr2217498688chr2217054947571DRB1-0909DAEYGASPEQVAASN318
IGFBP2-XRCC5chr2217498688chr2217054947571DRB1-0909RDAEYGASPEQVAAS217

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Fusion breakpoint peptide structures of IGFBP2-XRCC5

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
10639YGASPEQVAASNQLIGFBP2XRCC5chr2217498688chr2217054947571

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of IGFBP2-XRCC5

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-B14:023BVN10639YGASPEQVAASNQL-7.15543-7.26883
HLA-B14:023BVN10639YGASPEQVAASNQL-4.77435-5.80965
HLA-B52:013W3910639YGASPEQVAASNQL-6.80875-6.92215
HLA-B52:013W3910639YGASPEQVAASNQL-4.20386-5.23916
HLA-A11:014UQ210639YGASPEQVAASNQL-7.5194-8.5547
HLA-A11:014UQ210639YGASPEQVAASNQL-6.9601-7.0735
HLA-A24:025HGA10639YGASPEQVAASNQL-7.52403-7.63743
HLA-A24:025HGA10639YGASPEQVAASNQL-5.82433-6.85963
HLA-B27:056PYJ10639YGASPEQVAASNQL-3.28285-4.31815
HLA-B44:053DX810639YGASPEQVAASNQL-5.91172-6.94702
HLA-B44:053DX810639YGASPEQVAASNQL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of IGFBP2-XRCC5

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
IGFBP2-XRCC5chr2217498688chr22170549471120EQVAASNQLTTGCAGCGAGTAACCAGCTCATAAATC
IGFBP2-XRCC5chr2217498688chr2217054947414AEYGASPEQVATGGCGCCAGCCCGGAGCAGGTTGCAGCGA
IGFBP2-XRCC5chr2217498688chr2217054947415AEYGASPEQVAATGGCGCCAGCCCGGAGCAGGTTGCAGCGAGTA
IGFBP2-XRCC5chr2217498688chr2217054947920SPEQVAASNQLAGCAGGTTGCAGCGAGTAACCAGCTCATAAATC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
IGFBP2-XRCC5chr2217498688chr2217054947217RDAEYGASPEQVAASCCGAGTATGGCGCCAGCCCGGAGCAGGTTGCAGCGAGTAACCAGC
IGFBP2-XRCC5chr2217498688chr2217054947318DAEYGASPEQVAASNAGTATGGCGCCAGCCCGGAGCAGGTTGCAGCGAGTAACCAGCTCA

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Information of the samples that have these potential fusion neoantigens of IGFBP2-XRCC5

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
OVIGFBP2-XRCC5chr2217498688ENST00000233809chr2217054947ENST00000392132TCGA-29-1695

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Potential target of CAR-T therapy development for IGFBP2-XRCC5

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 IGFBP2-XRCC5

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 IGFBP2-XRCC5

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