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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:PAN3-KPNA3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PAN3-KPNA3
FusionPDB ID: 62523
FusionGDB2.0 ID: 62523
HgeneTgene
Gene symbol

PAN3

KPNA3

Gene ID

255967

3839

Gene namepoly(A) specific ribonuclease subunit PAN3karyopherin subunit alpha 3
Synonyms-IPOA4|SRP1|SRP1gamma|SRP4|hSRP1
Cytomap

13q12.2

13q14.2

Type of geneprotein-codingprotein-coding
DescriptionPAN2-PAN3 deadenylation complex subunit PAN3PAB-dependent poly(A)-specific ribonuclease subunit 3PAB-dependent poly(A)-specific ribonuclease subunit PAN3PAB1P-dependent poly(A)-nucleasePAB1P-dependent poly(A)-specific ribonucleasePABP-dependent poly(importin subunit alpha-4SRP1-gammaimportin alpha 4importin alpha Q2importin alpha-3importin subunit alpha-3karyopherin alpha 3 (importin alpha 4)qip2
Modification date2020032020200313
UniProtAcc.

O00505

Main function of 5'-partner protein: FUNCTION: Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. Recognizes NLSs of influenza A virus nucleoprotein probably through ARM repeats 7-9.
Ensembl transtripts involved in fusion geneENST idsENST00000380958, ENST00000399613, 
ENST00000282391, ENST00000483842, 
ENST00000261667, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 9 X 12=205211 X 9 X 5=495
# samples 2011
** MAII scorelog2(20/2052*10)=-3.35895882583233
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/495*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PAN3 [Title/Abstract] AND KPNA3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PAN3 [Title/Abstract] AND KPNA3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PAN3(28752072)-KPNA3(50321129), # samples:1
Anticipated loss of major functional domain due to fusion event.PAN3-KPNA3 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.
PAN3-KPNA3 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.
PAN3-KPNA3 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.
PAN3-KPNA3 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


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/chr13:28752072/chr13:50321129)
- 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 PAN3 (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 KPNA3 (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)
ENST00000380958PAN3chr1328752072+ENST00000261667KPNA3chr1350321129-48288421522338728
ENST00000399613PAN3chr1328752072+ENST00000261667KPNA3chr1350321129-4301315481811587

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
ENST00000380958ENST00000261667PAN3chr1328752072+KPNA3chr1350321129-0.0002734240.9997266
ENST00000399613ENST00000261667PAN3chr1328752072+KPNA3chr1350321129-0.0001802890.9998197

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 PAN3-KPNA3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PAN3chr1328752072KPNA3chr135032112931589NDFGALNISQRRKTMRRHRNEVTVEL
PAN3chr1328752072KPNA3chr1350321129842230NDFGALNISQRRKTMRRHRNEVTVEL

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Potential FusionNeoAntigen Information of PAN3-KPNA3 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.
PAN3-KPNA3_28752072_50321129.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)
PAN3-KPNA3chr1328752072chr1350321129842HLA-C16:01ISQRRKTM0.88240.9822715
PAN3-KPNA3chr1328752072chr1350321129842HLA-A30:01SQRRKTMRR0.97440.8102817
PAN3-KPNA3chr1328752072chr1350321129842HLA-B08:12NISQRRKTM0.6670.5764615

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Potential FusionNeoAntigen Information of PAN3-KPNA3 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.
PAN3-KPNA3_28752072_50321129.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)
PAN3-KPNA3chr1328752072chr1350321129842DRB1-1170ALNISQRRKTMRRHR419
PAN3-KPNA3chr1328752072chr1350321129842DRB1-1315ALNISQRRKTMRRHR419
PAN3-KPNA3chr1328752072chr1350321129842DRB1-1357ALNISQRRKTMRRHR419
PAN3-KPNA3chr1328752072chr1350321129842DRB1-1361ALNISQRRKTMRRHR419
PAN3-KPNA3chr1328752072chr1350321129842DRB1-1361GALNISQRRKTMRRH318
PAN3-KPNA3chr1328752072chr1350321129842DRB1-1376FGALNISQRRKTMRR217

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Fusion breakpoint peptide structures of PAN3-KPNA3

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
6212NISQRRKTMRRHRNPAN3KPNA3chr1328752072chr1350321129842

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PAN3-KPNA3

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-B14:023BVN6212NISQRRKTMRRHRN-7.15543-7.26883
HLA-B14:023BVN6212NISQRRKTMRRHRN-4.77435-5.80965
HLA-B52:013W396212NISQRRKTMRRHRN-6.80875-6.92215
HLA-B52:013W396212NISQRRKTMRRHRN-4.20386-5.23916
HLA-A11:014UQ26212NISQRRKTMRRHRN-7.5194-8.5547
HLA-A11:014UQ26212NISQRRKTMRRHRN-6.9601-7.0735
HLA-A24:025HGA6212NISQRRKTMRRHRN-7.52403-7.63743
HLA-A24:025HGA6212NISQRRKTMRRHRN-5.82433-6.85963
HLA-B27:056PYJ6212NISQRRKTMRRHRN-3.28285-4.31815
HLA-B44:053DX86212NISQRRKTMRRHRN-5.91172-6.94702
HLA-B44:053DX86212NISQRRKTMRRHRN-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PAN3-KPNA3

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
PAN3-KPNA3chr1328752072chr1350321129615NISQRRKTMAACATCTCTCAGAGACGAAAGACAATG
PAN3-KPNA3chr1328752072chr1350321129715ISQRRKTMATCTCTCAGAGACGAAAGACAATG
PAN3-KPNA3chr1328752072chr1350321129817SQRRKTMRRTCTCAGAGACGAAAGACAATGCGAAGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PAN3-KPNA3chr1328752072chr1350321129217FGALNISQRRKTMRRTTTGGTGCCCTCAACATCTCTCAGAGACGAAAGACAATGCGAAGA
PAN3-KPNA3chr1328752072chr1350321129318GALNISQRRKTMRRHGGTGCCCTCAACATCTCTCAGAGACGAAAGACAATGCGAAGACAT
PAN3-KPNA3chr1328752072chr1350321129419ALNISQRRKTMRRHRGCCCTCAACATCTCTCAGAGACGAAAGACAATGCGAAGACATAGA

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Information of the samples that have these potential fusion neoantigens of PAN3-KPNA3

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
ESCAPAN3-KPNA3chr1328752072ENST00000380958chr1350321129ENST00000261667TCGA-JY-A939

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Potential target of CAR-T therapy development for PAN3-KPNA3

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 PAN3-KPNA3

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 PAN3-KPNA3

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