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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:LRP1-BCAN

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LRP1-BCAN
FusionPDB ID: 49728
FusionGDB2.0 ID: 49728
HgeneTgene
Gene symbol

LRP1

BCAN

Gene ID

10438

63827

Gene nameC1D nuclear receptor corepressorbrevican
SynonymsLRP1|Rrp47|SUN-CoR|SUNCOR|hC1DBEHAB|CSPG7
Cytomap

2p14

1q23.1

Type of geneprotein-codingprotein-coding
Descriptionnuclear nucleic acid-binding protein C1DC1D DNA-binding proteinC1D nuclear receptor co-repressornuclear DNA-binding proteinsmall unique nuclear receptor co-repressorsmall unique nuclear receptor corepressorbrevican core proteinbrain-enriched hyaluronan-binding proteinchondroitin sulfate proteoglycan 7chondroitin sulfate proteoglycan BEHAB
Modification date2020031320200313
UniProtAcc

Q9NZR2

Main function of 5'-partner protein: FUNCTION: Potential cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis.

Q96GW7

Main function of 5'-partner protein: FUNCTION: May play a role in the terminally differentiating and the adult nervous system during postnatal development. Could stabilize interactions between hyaluronan (HA) and brain proteoglycans.
Ensembl transtripts involved in fusion geneENST idsENST00000243077, ENST00000338962, 
ENST00000553277, ENST00000553446, 
ENST00000554174, 
ENST00000361588, 
ENST00000329117, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 27 X 12=74523 X 1 X 2=6
# samples 263
** MAII scorelog2(26/7452*10)=-4.84104414591318
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/6*10)=2.32192809488736
Fusion gene context

PubMed: LRP1 [Title/Abstract] AND BCAN [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LRP1 [Title/Abstract] AND BCAN [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LRP1(57596320)-BCAN(156627467), # samples:1
Anticipated loss of major functional domain due to fusion event.LRP1-BCAN 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.
LRP1-BCAN 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.
LRP1-BCAN 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.
LRP1-BCAN 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/chr12:57596320/chr1:156627467)
- 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 LRP1 (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 BCAN (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)
ENST00000243077LRP1chr1257596320+ENST00000329117BCANchr1156627467+1209811177442117033753

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
ENST00000243077ENST00000329117LRP1chr1257596320+BCANchr1156627467+0.0049223050.99507767

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 LRP1-BCAN

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LRP1chr1257596320BCANchr1156627467111773579NDCGDNSDEESCNRYREYQWIGLNDR

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Potential FusionNeoAntigen Information of LRP1-BCAN 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.
LRP1-BCAN_57596320_156627467.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)
LRP1-BCANchr1257596320chr115662746711177HLA-B18:01DEESCNRY0.99860.807715
LRP1-BCANchr1257596320chr115662746711177HLA-B44:03EESCNRYREY0.99540.7547818
LRP1-BCANchr1257596320chr115662746711177HLA-B18:01DEESCNRYREY0.99570.7219718
LRP1-BCANchr1257596320chr115662746711177HLA-B18:08DEESCNRY0.99870.6555715
LRP1-BCANchr1257596320chr115662746711177HLA-B18:05DEESCNRY0.99860.807715
LRP1-BCANchr1257596320chr115662746711177HLA-B18:06DEESCNRY0.99830.7995715
LRP1-BCANchr1257596320chr115662746711177HLA-B18:03DEESCNRY0.99810.7979715
LRP1-BCANchr1257596320chr115662746711177HLA-B18:11DEESCNRY0.98560.7611715
LRP1-BCANchr1257596320chr115662746711177HLA-C06:02NRYREYQWI0.05590.98271221
LRP1-BCANchr1257596320chr115662746711177HLA-C06:17NRYREYQWI0.05590.98271221
LRP1-BCANchr1257596320chr115662746711177HLA-B44:26EESCNRYREY0.99540.7547818
LRP1-BCANchr1257596320chr115662746711177HLA-B44:13EESCNRYREY0.99540.7547818
LRP1-BCANchr1257596320chr115662746711177HLA-B44:07EESCNRYREY0.99540.7547818
LRP1-BCANchr1257596320chr115662746711177HLA-B18:05DEESCNRYREY0.99570.7219718

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Potential FusionNeoAntigen Information of LRP1-BCAN 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 LRP1-BCAN

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
8462SDEESCNRYREYQWLRP1BCANchr1257596320chr115662746711177

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LRP1-BCAN

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-B14:023BVN8462SDEESCNRYREYQW-7.15543-7.26883
HLA-B14:023BVN8462SDEESCNRYREYQW-4.77435-5.80965
HLA-B52:013W398462SDEESCNRYREYQW-6.80875-6.92215
HLA-B52:013W398462SDEESCNRYREYQW-4.20386-5.23916
HLA-A11:014UQ28462SDEESCNRYREYQW-7.5194-8.5547
HLA-A11:014UQ28462SDEESCNRYREYQW-6.9601-7.0735
HLA-A24:025HGA8462SDEESCNRYREYQW-7.52403-7.63743
HLA-A24:025HGA8462SDEESCNRYREYQW-5.82433-6.85963
HLA-B27:056PYJ8462SDEESCNRYREYQW-3.28285-4.31815
HLA-B44:053DX88462SDEESCNRYREYQW-5.91172-6.94702
HLA-B44:053DX88462SDEESCNRYREYQW-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of LRP1-BCAN

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
LRP1-BCANchr1257596320chr11566274671221NRYREYQWIGCAACCGGTACCGGGAGTACCAGTGGA
LRP1-BCANchr1257596320chr1156627467715DEESCNRYCCGATGAAGAGAGCTGCAACCGGT
LRP1-BCANchr1257596320chr1156627467718DEESCNRYREYCCGATGAAGAGAGCTGCAACCGGTACCGGGAGT
LRP1-BCANchr1257596320chr1156627467818EESCNRYREYATGAAGAGAGCTGCAACCGGTACCGGGAGT

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 LRP1-BCAN

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
LGGLRP1-BCANchr1257596320ENST00000243077chr1156627467ENST00000329117TCGA-CS-6186-01A

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Potential target of CAR-T therapy development for LRP1-BCAN

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 LRP1-BCAN

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 LRP1-BCAN

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