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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:PAPD4-NUP214

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PAPD4-NUP214
FusionPDB ID: 62576
FusionGDB2.0 ID: 62576
HgeneTgene
Gene symbol

PAPD4

NUP214

Gene ID

167153

8021

Gene nameterminal nucleotidyltransferase 2nucleoporin 214
SynonymsAPD4|GLD2|PAPD4|TUT2CAIN|CAN|IIAE9
Cytomap

5q14.1

9q34.13

Type of geneprotein-codingprotein-coding
Descriptionpoly(A) RNA polymerase GLD2PAP associated domain containing 4PAP-associated domain-containing protein 4TUTase 2hGLD-2poly(A) RNA polymerase D4, non-canonicalterminal uridylyltransferase 2nuclear pore complex protein Nup214CAN protein, putative oncogenenucleoporin 214kDa
Modification date2020032220200322
UniProtAcc.

P35658

Main function of 5'-partner protein: FUNCTION: Part of the nuclear pore complex (PubMed:9049309). Has a critical role in nucleocytoplasmic transport (PubMed:31178128). May serve as a docking site in the receptor-mediated import of substrates across the nuclear pore complex (PubMed:31178128, PubMed:8108440). {ECO:0000269|PubMed:31178128, ECO:0000269|PubMed:9049309, ECO:0000303|PubMed:8108440}.; FUNCTION: (Microbial infection) Required for capsid disassembly of the human adenovirus 5 (HadV-5) leading to release of the viral genome to the nucleus (in vitro). {ECO:0000269|PubMed:25410864}.
Ensembl transtripts involved in fusion geneENST idsENST00000296783, ENST00000423041, 
ENST00000428308, ENST00000453514, 
ENST00000504233, ENST00000502269, 
ENST00000465486, ENST00000359428, 
ENST00000411637, ENST00000451030, 
ENST00000483497, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 3 X 3=3619 X 26 X 11=5434
# samples 429
** MAII scorelog2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0		log2(29/5434*10)=-4.22788976020704
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PAPD4 [Title/Abstract] AND NUP214 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PAPD4 [Title/Abstract] AND NUP214 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PAPD4(78952824)-NUP214(134090599), # samples:1
Anticipated loss of major functional domain due to fusion event.PAPD4-NUP214 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.
PAPD4-NUP214 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.
PAPD4-NUP214 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.
PAPD4-NUP214 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
HgenePAPD4

GO:0043489

RNA stabilization

23200856

HgenePAPD4

GO:0043631

RNA polyadenylation

15070731

HgenePAPD4

GO:2000626

negative regulation of miRNA catabolic process

23200856



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/chr5:78952824/chr9:134090599)
- 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 PAPD4 (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 NUP214 (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)
ENST00000453514PAPD4chr578952824+ENST00000359428NUP214chr9134090599+362817646932444583
ENST00000453514PAPD4chr578952824+ENST00000411637NUP214chr9134090599+362117646932444583
ENST00000453514PAPD4chr578952824+ENST00000451030NUP214chr9134090599+265917646932444583
ENST00000453514PAPD4chr578952824+ENST00000483497NUP214chr9134090599+266117646932444583
ENST00000423041PAPD4chr578952824+ENST00000359428NUP214chr9134090599+332814644052144579
ENST00000423041PAPD4chr578952824+ENST00000411637NUP214chr9134090599+332114644052144579
ENST00000423041PAPD4chr578952824+ENST00000451030NUP214chr9134090599+235914644052144579
ENST00000423041PAPD4chr578952824+ENST00000483497NUP214chr9134090599+236114644052144579
ENST00000504233PAPD4chr578952824+ENST00000359428NUP214chr9134090599+348416206782300540
ENST00000504233PAPD4chr578952824+ENST00000411637NUP214chr9134090599+347716206782300540
ENST00000504233PAPD4chr578952824+ENST00000451030NUP214chr9134090599+251516206782300540
ENST00000504233PAPD4chr578952824+ENST00000483497NUP214chr9134090599+251716206782300540
ENST00000428308PAPD4chr578952824+ENST00000359428NUP214chr9134090599+337715134422193583
ENST00000428308PAPD4chr578952824+ENST00000411637NUP214chr9134090599+337015134422193583
ENST00000428308PAPD4chr578952824+ENST00000451030NUP214chr9134090599+240815134422193583
ENST00000428308PAPD4chr578952824+ENST00000483497NUP214chr9134090599+241015134422193583
ENST00000296783PAPD4chr578952824+ENST00000359428NUP214chr9134090599+323413702992050583
ENST00000296783PAPD4chr578952824+ENST00000411637NUP214chr9134090599+322713702992050583
ENST00000296783PAPD4chr578952824+ENST00000451030NUP214chr9134090599+226513702992050583
ENST00000296783PAPD4chr578952824+ENST00000483497NUP214chr9134090599+226713702992050583

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
ENST00000453514ENST00000359428PAPD4chr578952824+NUP214chr9134090599+0.0077508480.99224913
ENST00000453514ENST00000411637PAPD4chr578952824+NUP214chr9134090599+0.0075914610.9924085
ENST00000453514ENST00000451030PAPD4chr578952824+NUP214chr9134090599+0.0057218090.9942782
ENST00000453514ENST00000483497PAPD4chr578952824+NUP214chr9134090599+0.0055906990.99440926
ENST00000423041ENST00000359428PAPD4chr578952824+NUP214chr9134090599+0.0091349070.99086505
ENST00000423041ENST00000411637PAPD4chr578952824+NUP214chr9134090599+0.0088844540.99111557
ENST00000423041ENST00000451030PAPD4chr578952824+NUP214chr9134090599+0.0063315250.9936685
ENST00000423041ENST00000483497PAPD4chr578952824+NUP214chr9134090599+0.0061446260.9938553
ENST00000504233ENST00000359428PAPD4chr578952824+NUP214chr9134090599+0.0087219080.9912781
ENST00000504233ENST00000411637PAPD4chr578952824+NUP214chr9134090599+0.0085443030.99145573
ENST00000504233ENST00000451030PAPD4chr578952824+NUP214chr9134090599+0.0064033630.9935967
ENST00000504233ENST00000483497PAPD4chr578952824+NUP214chr9134090599+0.0062109770.993789
ENST00000428308ENST00000359428PAPD4chr578952824+NUP214chr9134090599+0.0097222570.9902777
ENST00000428308ENST00000411637PAPD4chr578952824+NUP214chr9134090599+0.0094120120.99058795
ENST00000428308ENST00000451030PAPD4chr578952824+NUP214chr9134090599+0.0069760620.9930239
ENST00000428308ENST00000483497PAPD4chr578952824+NUP214chr9134090599+0.0067181130.99328184
ENST00000296783ENST00000359428PAPD4chr578952824+NUP214chr9134090599+0.0085511930.9914488
ENST00000296783ENST00000411637PAPD4chr578952824+NUP214chr9134090599+0.008301740.99169827
ENST00000296783ENST00000451030PAPD4chr578952824+NUP214chr9134090599+0.0057501220.99424994
ENST00000296783ENST00000483497PAPD4chr578952824+NUP214chr9134090599+0.0056239630.99437606

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 PAPD4-NUP214

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PAPD4chr578952824NUP214chr91340905991370357PEPILPSLQKIYPQSSSSSGSVFGSG
PAPD4chr578952824NUP214chr91340905991464353PEPILPSLQKIYPQSSSSSGSVFGSG
PAPD4chr578952824NUP214chr91340905991513357PEPILPSLQKIYPQSSSSSGSVFGSG
PAPD4chr578952824NUP214chr91340905991620314PEPILPSLQKIYPQSSSSSGSVFGSG
PAPD4chr578952824NUP214chr91340905991764357PEPILPSLQKIYPQSSSSSGSVFGSG

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Potential FusionNeoAntigen Information of PAPD4-NUP214 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.
PAPD4-NUP214_78952824_134090599.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)
PAPD4-NUP214chr578952824chr91340905991370HLA-A30:08KIYPQSSSS0.72920.7397918
PAPD4-NUP214chr578952824chr91340905991370HLA-B67:01YPQSSSSSGSV0.81790.80931122

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Potential FusionNeoAntigen Information of PAPD4-NUP214 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.
PAPD4-NUP214_78952824_134090599.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)
PAPD4-NUP214chr578952824chr91340905991370DRB1-0413LQKIYPQSSSSSGSV722
PAPD4-NUP214chr578952824chr91340905991370DRB1-0413SLQKIYPQSSSSSGS621
PAPD4-NUP214chr578952824chr91340905991370DRB1-0437LQKIYPQSSSSSGSV722
PAPD4-NUP214chr578952824chr91340905991370DRB1-0440LQKIYPQSSSSSGSV722
PAPD4-NUP214chr578952824chr91340905991370DRB1-0444LQKIYPQSSSSSGSV722
PAPD4-NUP214chr578952824chr91340905991370DRB1-0444SLQKIYPQSSSSSGS621
PAPD4-NUP214chr578952824chr91340905991370DRB1-0468LQKIYPQSSSSSGSV722
PAPD4-NUP214chr578952824chr91340905991370DRB1-0470LQKIYPQSSSSSGSV722
PAPD4-NUP214chr578952824chr91340905991370DRB1-0470SLQKIYPQSSSSSGS621
PAPD4-NUP214chr578952824chr91340905991370DRB1-0473LQKIYPQSSSSSGSV722
PAPD4-NUP214chr578952824chr91340905991370DRB1-0479LQKIYPQSSSSSGSV722
PAPD4-NUP214chr578952824chr91340905991370DRB1-0479SLQKIYPQSSSSSGS621
PAPD4-NUP214chr578952824chr91340905991370DRB1-1201PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1203PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1205PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1206PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1207PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1208PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1210PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1211PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1212PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1213PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1214PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1215PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1217PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1218PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1219PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1220PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1221PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1223PEPILPSLQKIYPQS015
PAPD4-NUP214chr578952824chr91340905991370DRB1-1377PEPILPSLQKIYPQS015

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Fusion breakpoint peptide structures of PAPD4-NUP214

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
8778SLQKIYPQSSSSSGPAPD4NUP214chr578952824chr91340905991370

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PAPD4-NUP214

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-B14:023BVN8778SLQKIYPQSSSSSG-7.15543-7.26883
HLA-B14:023BVN8778SLQKIYPQSSSSSG-4.77435-5.80965
HLA-B52:013W398778SLQKIYPQSSSSSG-6.80875-6.92215
HLA-B52:013W398778SLQKIYPQSSSSSG-4.20386-5.23916
HLA-A11:014UQ28778SLQKIYPQSSSSSG-7.5194-8.5547
HLA-A11:014UQ28778SLQKIYPQSSSSSG-6.9601-7.0735
HLA-A24:025HGA8778SLQKIYPQSSSSSG-7.52403-7.63743
HLA-A24:025HGA8778SLQKIYPQSSSSSG-5.82433-6.85963
HLA-B27:056PYJ8778SLQKIYPQSSSSSG-3.28285-4.31815
HLA-B44:053DX88778SLQKIYPQSSSSSG-5.91172-6.94702
HLA-B44:053DX88778SLQKIYPQSSSSSG-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PAPD4-NUP214

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
PAPD4-NUP214chr578952824chr91340905991122YPQSSSSSGSVTACCCACAATCATCCTCTTCCAGTGGTAGCGTG
PAPD4-NUP214chr578952824chr9134090599918KIYPQSSSSAAAATTTACCCACAATCATCCTCTTCC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PAPD4-NUP214chr578952824chr9134090599015PEPILPSLQKIYPQSCCTGAACCCATCCTTCCATCCCTCCAAAAAATTTACCCACAATCA
PAPD4-NUP214chr578952824chr9134090599621SLQKIYPQSSSSSGSTCCCTCCAAAAAATTTACCCACAATCATCCTCTTCCAGTGGTAGC
PAPD4-NUP214chr578952824chr9134090599722LQKIYPQSSSSSGSVCTCCAAAAAATTTACCCACAATCATCCTCTTCCAGTGGTAGCGTG

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Information of the samples that have these potential fusion neoantigens of PAPD4-NUP214

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
Non-CancerPAPD4-NUP214chr578952824ENST00000296783chr9134090599ENST00000359428ERR315488

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Potential target of CAR-T therapy development for PAPD4-NUP214

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 PAPD4-NUP214

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 PAPD4-NUP214

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
TgeneNUP214C0025958Microcephaly1GENOMICS_ENGLAND
TgeneNUP214C0543888Epileptic encephalopathy1GENOMICS_ENGLAND
TgeneNUP214C1836830Developmental regression1GENOMICS_ENGLAND
TgeneNUP214C1961099Precursor T-Cell Lymphoblastic Leukemia-Lymphoma1ORPHANET