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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:PREB-FLNA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PREB-FLNA
FusionPDB ID: 68498
FusionGDB2.0 ID: 68498
HgeneTgene
Gene symbol

PREB

FLNA

Gene ID

10113

2316

Gene nameprolactin regulatory element bindingfilamin A
SynonymsSEC12ABP-280|ABPX|CSBS|CVD1|FGS2|FLN|FLN-A|FLN1|FMD|MNS|NHBP|OPD|OPD1|OPD2|XLVD|XMVD
Cytomap

2p23.3

Xq28

Type of geneprotein-codingprotein-coding
Descriptionprolactin regulatory element-binding proteinmammalian guanine nucleotide exchange factor mSec12filamin-Aactin binding protein 280alpha-filaminendothelial actin-binding proteinepididymis secretory sperm binding proteinfilamin A, alphafilamin-1non-muscle filamin
Modification date2020031320200313
UniProtAcc.

P21333

Main function of 5'-partner protein: FUNCTION: Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}.
Ensembl transtripts involved in fusion geneENST idsENST00000260643, ENST00000406567, 
ENST00000416802, 
ENST00000344736, 
ENST00000369856, ENST00000498491, 
ENST00000360319, ENST00000369850, 
ENST00000422373, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 5 X 2=4025 X 31 X 6=4650
# samples 531
** MAII scorelog2(5/40*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(31/4650*10)=-3.90689059560852
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PREB [Title/Abstract] AND FLNA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PREB [Title/Abstract] AND FLNA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PREB(27356400)-FLNA(153583440), # samples:1
Anticipated loss of major functional domain due to fusion event.PREB-FLNA 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.
PREB-FLNA 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.
PREB-FLNA 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.
PREB-FLNA 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
TgeneFLNA

GO:0016479

negative regulation of transcription by RNA polymerase I

22307607

TgeneFLNA

GO:0030334

regulation of cell migration

16291724

TgeneFLNA

GO:0031532

actin cytoskeleton reorganization

10051605

TgeneFLNA

GO:0034394

protein localization to cell surface

18322202

TgeneFLNA

GO:0043113

receptor clustering

10692483

TgeneFLNA

GO:0043433

negative regulation of DNA-binding transcription factor activity

15684392

TgeneFLNA

GO:0044319

wound healing, spreading of cells

16291724

TgeneFLNA

GO:0045184

establishment of protein localization

18322202

TgeneFLNA

GO:0051764

actin crosslink formation

10051605

TgeneFLNA

GO:0072659

protein localization to plasma membrane

24951510

TgeneFLNA

GO:0090307

mitotic spindle assembly

18548008

TgeneFLNA

GO:1901381

positive regulation of potassium ion transmembrane transport

24951510



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/chr2:27356400/chrX:153583440)
- 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 PREB (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 FLNA (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)
ENST00000260643PREBchr227356400-ENST00000360319FLNAchrX153583440-387757925435531099
ENST00000260643PREBchr227356400-ENST00000422373FLNAchrX153583440-387157925435531099
ENST00000260643PREBchr227356400-ENST00000369850FLNAchrX153583440-375557925435531099
ENST00000406567PREBchr227356400-ENST00000360319FLNAchrX153583440-381451619134901099
ENST00000406567PREBchr227356400-ENST00000422373FLNAchrX153583440-380851619134901099
ENST00000406567PREBchr227356400-ENST00000369850FLNAchrX153583440-369251619134901099

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
ENST00000260643ENST00000360319PREBchr227356400-FLNAchrX153583440-0.0022029210.99779713
ENST00000260643ENST00000422373PREBchr227356400-FLNAchrX153583440-0.0021924240.99780756
ENST00000260643ENST00000369850PREBchr227356400-FLNAchrX153583440-0.002743150.9972568
ENST00000406567ENST00000360319PREBchr227356400-FLNAchrX153583440-0.0021063330.99789363
ENST00000406567ENST00000422373PREBchr227356400-FLNAchrX153583440-0.0020955190.99790454
ENST00000406567ENST00000369850PREBchr227356400-FLNAchrX153583440-0.0026468070.9973532

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 PREB-FLNA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PREBchr227356400FLNAchrX153583440516108QAHQQQGNKAEKAGAGIGPTIQIGEE
PREBchr227356400FLNAchrX153583440516119KAGAGIGPTIQIGEETVITVDTKAAG
PREBchr227356400FLNAchrX153583440579108QAHQQQGNKAEKAGAGIGPTIQIGEE
PREBchr227356400FLNAchrX153583440579119KAGAGIGPTIQIGEETVITVDTKAAG

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Potential FusionNeoAntigen Information of PREB-FLNA 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.
PREB-FLNA_27356400_153583440.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)
PREB-FLNAchr227356400chrX153583440579HLA-B41:01GEETVITV0.92470.98391220
PREB-FLNAchr227356400chrX153583440579HLA-B48:01IQIGEETVI0.92050.5835918
PREB-FLNAchr227356400chrX153583440579HLA-B13:02IQIGEETVI0.63490.8058918
PREB-FLNAchr227356400chrX153583440579HLA-B13:01IQIGEETVI0.59950.9823918
PREB-FLNAchr227356400chrX153583440579HLA-B39:13IQIGEETVI0.43180.9375918
PREB-FLNAchr227356400chrX153583440579HLA-B52:01IQIGEETVI0.0980.994918
PREB-FLNAchr227356400chrX153583440579HLA-A02:21IQIGEETVITV0.99660.8871920
PREB-FLNAchr227356400chrX153583440579HLA-B13:02IQIGEETVITV0.95690.972920
PREB-FLNAchr227356400chrX153583440579HLA-B40:06GEETVITV0.99990.86561220
PREB-FLNAchr227356400chrX153583440579HLA-C08:15IGEETVITV0.99940.99031120
PREB-FLNAchr227356400chrX153583440579HLA-B40:04GEETVITV0.99920.83991220
PREB-FLNAchr227356400chrX153583440579HLA-B41:03GEETVITV0.9730.781220
PREB-FLNAchr227356400chrX153583440579HLA-C08:02IGEETVITV0.99940.99031120
PREB-FLNAchr227356400chrX153583440579HLA-B15:73IQIGEETVI0.980.9596918
PREB-FLNAchr227356400chrX153583440579HLA-B15:30IQIGEETVI0.97280.916918
PREB-FLNAchr227356400chrX153583440579HLA-B39:02IQIGEETVI0.50450.9406918
PREB-FLNAchr227356400chrX153583440579HLA-B40:21IQIGEETVI0.48050.5136918
PREB-FLNAchr227356400chrX153583440579HLA-A02:06IQIGEETVITV0.99660.8871920

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Potential FusionNeoAntigen Information of PREB-FLNA 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.
PREB-FLNA_27356400_153583440.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)
PREB-FLNAchr227356400chrX153583440579DRB1-0301IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0303IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0307IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0310IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0313IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0315IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0318IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0320IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0322IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0324IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0326IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0328IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0330IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0332IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0334IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0336IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0342IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0344IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0346IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0348IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0350IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0352IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0354IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0458IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0478IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-0906GPTIQIGEETVITVD621
PREB-FLNAchr227356400chrX153583440579DRB1-1107IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-1394IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-1476IGEETVITVDTKAAG1126
PREB-FLNAchr227356400chrX153583440579DRB1-1479IGEETVITVDTKAAG1126

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Fusion breakpoint peptide structures of PREB-FLNA

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
3041GPTIQIGEETVITVPREBFLNAchr227356400chrX153583440579

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PREB-FLNA

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-B14:023BVN3041GPTIQIGEETVITV-7.9962-8.1096
HLA-B14:023BVN3041GPTIQIGEETVITV-5.70842-6.74372
HLA-B52:013W393041GPTIQIGEETVITV-6.83737-6.95077
HLA-B52:013W393041GPTIQIGEETVITV-4.4836-5.5189
HLA-A11:014UQ23041GPTIQIGEETVITV-10.0067-10.1201
HLA-A11:014UQ23041GPTIQIGEETVITV-9.03915-10.0745
HLA-A24:025HGA3041GPTIQIGEETVITV-6.56204-6.67544
HLA-A24:025HGA3041GPTIQIGEETVITV-5.42271-6.45801
HLA-B44:053DX83041GPTIQIGEETVITV-7.85648-8.89178
HLA-B44:053DX83041GPTIQIGEETVITV-5.3978-5.5112
HLA-A02:016TDR3041GPTIQIGEETVITV-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PREB-FLNA

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
PREB-FLNAchr227356400chrX1535834401120IGEETVITVAGGCCGGTGCTGGCATCGGCCCCACCA
PREB-FLNAchr227356400chrX1535834401220GEETVITVCCGGTGCTGGCATCGGCCCCACCA
PREB-FLNAchr227356400chrX153583440918IQIGEETVICAGAGAAGGCCGGTGCTGGCATCGGCC
PREB-FLNAchr227356400chrX153583440920IQIGEETVITVCAGAGAAGGCCGGTGCTGGCATCGGCCCCACCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PREB-FLNAchr227356400chrX1535834401126IGEETVITVDTKAAGAGGCCGGTGCTGGCATCGGCCCCACCATTCAGATTGGGGAGGAGA
PREB-FLNAchr227356400chrX153583440621GPTIQIGEETVITVDGCAACAAGGCAGAGAAGGCCGGTGCTGGCATCGGCCCCACCATTC

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Information of the samples that have these potential fusion neoantigens of PREB-FLNA

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
BRCAPREB-FLNAchr227356400ENST00000260643chrX153583440ENST00000360319TCGA-AR-A1AK-01A

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Potential target of CAR-T therapy development for PREB-FLNA

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 PREB-FLNA

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 PREB-FLNA

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