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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:NAP1L4-CFTR

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NAP1L4-CFTR
FusionPDB ID: 57200
FusionGDB2.0 ID: 57200
HgeneTgene
Gene symbol

NAP1L4

CFTR

Gene ID

4676

1080

Gene namenucleosome assembly protein 1 like 4CF transmembrane conductance regulator
SynonymsNAP1L4b|NAP2|NAP2L|hNAP2ABC35|ABCC7|CF|CFTR/MRP|MRP7|TNR-CFTR|dJ760C5.1
Cytomap

11p15.4

7q31.2

Type of geneprotein-codingprotein-coding
Descriptionnucleosome assembly protein 1-like 4NAP-2nucleosome assembly protein 1-like 4bnucleosome assembly protein 2cystic fibrosis transmembrane conductance regulatorcAMP-dependent chloride channelchannel conductance-controlling ATPasecystic fibrosis transmembrane conductance regulatingcystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-f
Modification date2020032220200329
UniProtAcc

Q99733

Main function of 5'-partner protein: FUNCTION: Acts as histone chaperone in nucleosome assembly. {ECO:0000269|PubMed:9325046}.

P13569

Main function of 5'-partner protein: FUNCTION: Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:15010471, PubMed:12588899, PubMed:17036051, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:1712898, PubMed:8910473, PubMed:9804160, PubMed:12529365, PubMed:17182731, PubMed:26846474, PubMed:28087700). Channel activity is coupled to ATP hydrolysis (PubMed:8910473). The ion channel is also permeable to HCO(3-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22178883, PubMed:22121115, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17434346, PubMed:27941075, PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810). {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:14668433, ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:16645176, ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:19019741, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064, ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:26823428, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27714810, ECO:0000269|PubMed:27941075, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:9804160, ECO:0000305|PubMed:19923167}.
Ensembl transtripts involved in fusion geneENST idsENST00000380542, ENST00000526115, 
ENST00000469089, 
ENST00000608965, 
ENST00000003084, ENST00000454343, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 18 X 7=163813 X 15 X 10=1950
# samples 1813
** MAII scorelog2(18/1638*10)=-3.18586654531133
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/1950*10)=-3.90689059560852
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NAP1L4 [Title/Abstract] AND CFTR [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NAP1L4 [Title/Abstract] AND CFTR [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NAP1L4(2972489)-CFTR(117227793), # samples:2
Anticipated loss of major functional domain due to fusion event.NAP1L4-CFTR 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.
NAP1L4-CFTR 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.
NAP1L4-CFTR 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.
NAP1L4-CFTR 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.
NAP1L4-CFTR seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
NAP1L4-CFTR seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NAP1L4-CFTR seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
NAP1L4-CFTR 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
HgeneNAP1L4

GO:0006334

nucleosome assembly

9325046

TgeneCFTR

GO:0015701

bicarbonate transport

15010471|19019741

TgeneCFTR

GO:0034976

response to endoplasmic reticulum stress

21884936|28067262

TgeneCFTR

GO:1902476

chloride transmembrane transport

11524016|11707463|19019741

TgeneCFTR

GO:1902943

positive regulation of voltage-gated chloride channel activity

22006324

TgeneCFTR

GO:1904322

cellular response to forskolin

15010471|19621064



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/chr11:2972489/chr7:117227793)
- 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 NAP1L4 (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 CFTR (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)
ENST00000526115NAP1L4chr112972489-ENST00000003084CFTRchr7117227793+5818140628442641326
ENST00000526115NAP1L4chr112972489-ENST00000454343CFTRchr7117227793+5822140628442641326
ENST00000526115NAP1L4chr112972488-ENST00000003084CFTRchr7117227792+5818140628442641326
ENST00000526115NAP1L4chr112972488-ENST00000454343CFTRchr7117227792+5822140628442641326

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
ENST00000526115ENST00000003084NAP1L4chr112972489-CFTRchr7117227793+0.0002271570.99977285
ENST00000526115ENST00000454343NAP1L4chr112972489-CFTRchr7117227793+0.0002258560.99977416
ENST00000526115ENST00000003084NAP1L4chr112972488-CFTRchr7117227792+0.0002271570.99977285
ENST00000526115ENST00000454343NAP1L4chr112972488-CFTRchr7117227792+0.0002258560.99977416

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 NAP1L4-CFTR

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NAP1L4chr112972488CFTRchr71172277921406374EGEDEDDAEINPKDISKFAEKDNIVL
NAP1L4chr112972489CFTRchr71172277931406374EGEDEDDAEINPKDISKFAEKDNIVL

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Potential FusionNeoAntigen Information of NAP1L4-CFTR 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.
NAP1L4-CFTR_2972488_117227792.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)
NAP1L4-CFTRchr112972488chr71172277921406HLA-B45:01AEINPKDIS0.98640.7547716
NAP1L4-CFTRchr112972488chr71172277921406HLA-B41:01AEINPKDIS0.30490.9161716
NAP1L4-CFTRchr112972488chr71172277921406HLA-B44:03AEINPKDISKF10.9372718
NAP1L4-CFTRchr112972488chr71172277921406HLA-B35:24NPKDISKF0.96440.87791018
NAP1L4-CFTRchr112972488chr71172277921406HLA-B18:07NPKDISKF0.77340.81611018
NAP1L4-CFTRchr112972488chr71172277921406HLA-A25:01EINPKDISKF0.99710.8141818
NAP1L4-CFTRchr112972488chr71172277921406HLA-B44:26AEINPKDISKF10.9372718
NAP1L4-CFTRchr112972488chr71172277921406HLA-B15:53AEINPKDISKF10.8841718
NAP1L4-CFTRchr112972488chr71172277921406HLA-B44:13AEINPKDISKF10.9372718
NAP1L4-CFTRchr112972488chr71172277921406HLA-B44:07AEINPKDISKF10.9372718
NAP1L4-CFTRchr112972488chr71172277921406HLA-B40:04AEINPKDISKF0.99970.5659718
NAP1L4-CFTRchr112972488chr71172277921406HLA-B48:02AEINPKDISKF0.99970.8836718
NAP1L4-CFTRchr112972488chr71172277921406HLA-B41:03AEINPKDISKF0.99810.5858718

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Potential FusionNeoAntigen Information of NAP1L4-CFTR 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 NAP1L4-CFTR

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
985DAEINPKDISKFAENAP1L4CFTRchr112972488chr71172277921406

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NAP1L4-CFTR

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-B14:023BVN985DAEINPKDISKFAE-5.16857-5.28197
HLA-B14:023BVN985DAEINPKDISKFAE-4.21097-5.24627
HLA-B52:013W39985DAEINPKDISKFAE-4.32839-4.44179
HLA-B52:013W39985DAEINPKDISKFAE-4.10962-5.14492
HLA-A24:025HGA985DAEINPKDISKFAE-6.03661-6.15001
HLA-A24:025HGA985DAEINPKDISKFAE-5.99594-7.03124
HLA-B44:053DX8985DAEINPKDISKFAE-6.27779-6.39119
HLA-B44:053DX8985DAEINPKDISKFAE-4.76488-5.80018

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Vaccine Design for the FusionNeoAntigens of NAP1L4-CFTR

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
NAP1L4-CFTRchr112972488chr71172277921018NPKDISKFAACCCCAAGGACATCTCCAAGTTT
NAP1L4-CFTRchr112972488chr7117227792716AEINPKDISGCGGAAATTAACCCCAAGGACATCTCC
NAP1L4-CFTRchr112972488chr7117227792718AEINPKDISKFGCGGAAATTAACCCCAAGGACATCTCCAAGTTT
NAP1L4-CFTRchr112972488chr7117227792818EINPKDISKFGAAATTAACCCCAAGGACATCTCCAAGTTT

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 NAP1L4-CFTR

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
OVNAP1L4-CFTRchr112972488ENST00000526115chr7117227792ENST00000003084TCGA-24-1417

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Potential target of CAR-T therapy development for NAP1L4-CFTR

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
TgeneCFTRchr11:2972488chr7:117227792ENST0000000308410271014_103401481.0TransmembraneHelical%3B Name%3D10
TgeneCFTRchr11:2972488chr7:117227792ENST0000000308410271096_111601481.0TransmembraneHelical%3B Name%3D11
TgeneCFTRchr11:2972488chr7:117227792ENST0000000308410271131_115101481.0TransmembraneHelical%3B Name%3D12
TgeneCFTRchr11:2972488chr7:117227792ENST000000030841027859_87901481.0TransmembraneHelical%3B Name%3D7
TgeneCFTRchr11:2972488chr7:117227792ENST000000030841027919_93901481.0TransmembraneDiscontinuously helical%3B Name%3D8
TgeneCFTRchr11:2972488chr7:117227792ENST000000030841027991_101101481.0TransmembraneHelical%3B Name%3D9
TgeneCFTRchr11:2972488chr7:117227792ENST000004543439261014_103401420.0TransmembraneHelical%3B Name%3D10
TgeneCFTRchr11:2972488chr7:117227792ENST000004543439261096_111601420.0TransmembraneHelical%3B Name%3D11
TgeneCFTRchr11:2972488chr7:117227792ENST000004543439261131_115101420.0TransmembraneHelical%3B Name%3D12
TgeneCFTRchr11:2972488chr7:117227792ENST00000454343926859_87901420.0TransmembraneHelical%3B Name%3D7
TgeneCFTRchr11:2972488chr7:117227792ENST00000454343926919_93901420.0TransmembraneDiscontinuously helical%3B Name%3D8
TgeneCFTRchr11:2972488chr7:117227792ENST00000454343926991_101101420.0TransmembraneHelical%3B Name%3D9
TgeneCFTRchr11:2972489chr7:117227793ENST0000000308410271014_103401481.0TransmembraneHelical%3B Name%3D10
TgeneCFTRchr11:2972489chr7:117227793ENST0000000308410271096_111601481.0TransmembraneHelical%3B Name%3D11
TgeneCFTRchr11:2972489chr7:117227793ENST0000000308410271131_115101481.0TransmembraneHelical%3B Name%3D12
TgeneCFTRchr11:2972489chr7:117227793ENST000000030841027859_87901481.0TransmembraneHelical%3B Name%3D7
TgeneCFTRchr11:2972489chr7:117227793ENST000000030841027919_93901481.0TransmembraneDiscontinuously helical%3B Name%3D8
TgeneCFTRchr11:2972489chr7:117227793ENST000000030841027991_101101481.0TransmembraneHelical%3B Name%3D9
TgeneCFTRchr11:2972489chr7:117227793ENST000004543439261014_103401420.0TransmembraneHelical%3B Name%3D10
TgeneCFTRchr11:2972489chr7:117227793ENST000004543439261096_111601420.0TransmembraneHelical%3B Name%3D11
TgeneCFTRchr11:2972489chr7:117227793ENST000004543439261131_115101420.0TransmembraneHelical%3B Name%3D12
TgeneCFTRchr11:2972489chr7:117227793ENST00000454343926859_87901420.0TransmembraneHelical%3B Name%3D7
TgeneCFTRchr11:2972489chr7:117227793ENST00000454343926919_93901420.0TransmembraneDiscontinuously helical%3B Name%3D8
TgeneCFTRchr11:2972489chr7:117227793ENST00000454343926991_101101420.0TransmembraneHelical%3B Name%3D9

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 NAP1L4-CFTR

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 NAP1L4-CFTR

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