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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:LDLR-ASF1B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LDLR-ASF1B
FusionPDB ID: 44402
FusionGDB2.0 ID: 44402
HgeneTgene
Gene symbol

LDLR

ASF1B

Gene ID

3949

55723

Gene namelow density lipoprotein receptoranti-silencing function 1B histone chaperone
SynonymsFH|FHC|FHCL1|LDLCQ2CIA-II
Cytomap

19p13.2

19p13.12

Type of geneprotein-codingprotein-coding
Descriptionlow-density lipoprotein receptorLDL receptorlow-density lipoprotein receptor class A domain-containing protein 3histone chaperone ASF1BASF1 anti-silencing function 1 homolog BCCG1-interacting factor A-IIanti-silencing function protein 1 homolog BhAsf1hAsf1bhCIA-II
Modification date2020032220200313
UniProtAcc

Q5SW96

Main function of 5'-partner protein: FUNCTION: Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Required for trafficking of LRP2 to the endocytic recycling compartment which is necessary for LRP2 proteolysis, releasing a tail fragment which translocates to the nucleus and mediates transcriptional repression (By similarity). {ECO:0000250|UniProtKB:D3ZAR1, ECO:0000269|PubMed:15728179}.

Q9NVP2

Main function of 5'-partner protein: FUNCTION: Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly. Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly. Does not participate in replication-independent nucleosome deposition which is mediated by ASF1A and HIRA. Required for spermatogenesis. {ECO:0000269|PubMed:11897662, ECO:0000269|PubMed:12842904, ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15664198, ECO:0000269|PubMed:16151251}.
Ensembl transtripts involved in fusion geneENST idsENST00000455727, ENST00000535915, 
ENST00000545707, ENST00000557933, 
ENST00000558013, ENST00000558518, 
ENST00000560628, 
ENST00000263382, 
ENST00000474890, ENST00000592798, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 17 X 15=58657 X 5 X 6=210
# samples 338
** MAII scorelog2(33/5865*10)=-4.15159317867005
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/210*10)=-1.39231742277876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LDLR [Title/Abstract] AND ASF1B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LDLR [Title/Abstract] AND ASF1B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LDLR(11218190)-ASF1B(14237049), # samples:1
Anticipated loss of major functional domain due to fusion event.LDLR-ASF1B 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.
LDLR-ASF1B 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.
LDLR-ASF1B 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.
LDLR-ASF1B 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
TgeneASF1B

GO:0006335

DNA replication-dependent nucleosome assembly

14718166

TgeneASF1B

GO:0006336

DNA replication-independent nucleosome assembly

14718166



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/chr19:11218190/chr19:14237049)
- 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 LDLR (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 ASF1B (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)
ENST00000558518LDLRchr1911218190+ENST00000263382ASF1Bchr1914237049-257711271691626485
ENST00000558518LDLRchr1911218190+ENST00000592798ASF1Bchr1914237049-169011271691449426
ENST00000558518LDLRchr1911218190+ENST00000474890ASF1Bchr1914237049-166511271691515448
ENST00000557933LDLRchr1911218190+ENST00000263382ASF1Bchr1914237049-24771027691526485
ENST00000557933LDLRchr1911218190+ENST00000592798ASF1Bchr1914237049-15901027691349426
ENST00000557933LDLRchr1911218190+ENST00000474890ASF1Bchr1914237049-15651027691415448
ENST00000455727LDLRchr1911218190+ENST00000263382ASF1Bchr1914237049-1972522681021317
ENST00000455727LDLRchr1911218190+ENST00000592798ASF1Bchr1914237049-108552268844258
ENST00000455727LDLRchr1911218190+ENST00000474890ASF1Bchr1914237049-106052268910280
ENST00000535915LDLRchr1911218190+ENST00000263382ASF1Bchr1914237049-2353903681402444
ENST00000535915LDLRchr1911218190+ENST00000592798ASF1Bchr1914237049-1466903681225385
ENST00000535915LDLRchr1911218190+ENST00000474890ASF1Bchr1914237049-1441903681291407
ENST00000545707LDLRchr1911218190+ENST00000263382ASF1Bchr1914237049-2095645681144358
ENST00000545707LDLRchr1911218190+ENST00000592798ASF1Bchr1914237049-120864568967299
ENST00000545707LDLRchr1911218190+ENST00000474890ASF1Bchr1914237049-1183645681033321
ENST00000558013LDLRchr1911218190+ENST00000263382ASF1Bchr1914237049-24611011531510485
ENST00000558013LDLRchr1911218190+ENST00000592798ASF1Bchr1914237049-15741011531333426
ENST00000558013LDLRchr1911218190+ENST00000474890ASF1Bchr1914237049-15491011531399448

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
ENST00000558518ENST00000263382LDLRchr1911218190+ASF1Bchr1914237049-0.0090183270.99098164
ENST00000558518ENST00000592798LDLRchr1911218190+ASF1Bchr1914237049-0.0188154190.98118454
ENST00000558518ENST00000474890LDLRchr1911218190+ASF1Bchr1914237049-0.0105063720.9894936
ENST00000557933ENST00000263382LDLRchr1911218190+ASF1Bchr1914237049-0.0089965820.9910034
ENST00000557933ENST00000592798LDLRchr1911218190+ASF1Bchr1914237049-0.0192813150.98071873
ENST00000557933ENST00000474890LDLRchr1911218190+ASF1Bchr1914237049-0.0107280350.989272
ENST00000455727ENST00000263382LDLRchr1911218190+ASF1Bchr1914237049-0.0085509980.99144894
ENST00000455727ENST00000592798LDLRchr1911218190+ASF1Bchr1914237049-0.0167782590.98322177
ENST00000455727ENST00000474890LDLRchr1911218190+ASF1Bchr1914237049-0.0145658080.9854342
ENST00000535915ENST00000263382LDLRchr1911218190+ASF1Bchr1914237049-0.0066445140.9933555
ENST00000535915ENST00000592798LDLRchr1911218190+ASF1Bchr1914237049-0.0153559880.98464406
ENST00000535915ENST00000474890LDLRchr1911218190+ASF1Bchr1914237049-0.007186340.99281365
ENST00000545707ENST00000263382LDLRchr1911218190+ASF1Bchr1914237049-0.0046230670.99537694
ENST00000545707ENST00000592798LDLRchr1911218190+ASF1Bchr1914237049-0.0128776940.98712236
ENST00000545707ENST00000474890LDLRchr1911218190+ASF1Bchr1914237049-0.0052348970.99476504
ENST00000558013ENST00000263382LDLRchr1911218190+ASF1Bchr1914237049-0.0088389260.991161
ENST00000558013ENST00000592798LDLRchr1911218190+ASF1Bchr1914237049-0.018959350.98104066
ENST00000558013ENST00000474890LDLRchr1911218190+ASF1Bchr1914237049-0.0107625060.9892374

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 LDLR-ASF1B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LDLRchr1911218190ASF1Bchr19142370491011319DCRDWSDEPIKECDLEWKIIYVGSAE
LDLRchr1911218190ASF1Bchr19142370491027319DCRDWSDEPIKECDLEWKIIYVGSAE
LDLRchr1911218190ASF1Bchr19142370491127319DCRDWSDEPIKECDLEWKIIYVGSAE
LDLRchr1911218190ASF1Bchr1914237049522151DCRDWSDEPIKECDLEWKIIYVGSAE
LDLRchr1911218190ASF1Bchr1914237049645192DCRDWSDEPIKECDLEWKIIYVGSAE
LDLRchr1911218190ASF1Bchr1914237049903278DCRDWSDEPIKECDLEWKIIYVGSAE

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Potential FusionNeoAntigen Information of LDLR-ASF1B 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.
LDLR-ASF1B_11218190_14237049.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)
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B13:01KECDLEWKI0.97320.91051019
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B47:01KECDLEWKI0.85620.60371019
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B39:13KECDLEWKI0.04780.92191019
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B44:03KECDLEWKIIY0.99820.87131021
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B40:06KECDLEWKI0.99550.63751019
LDLR-ASF1Bchr1911218190chr1914237049522HLA-C05:09WSDEPIKECDL10.8742415
LDLR-ASF1Bchr1911218190chr1914237049522HLA-C08:15WSDEPIKECDL10.9153415
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B40:04KECDLEWKI0.98610.71941019
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B41:03KECDLEWKI0.44640.54581019
LDLR-ASF1Bchr1911218190chr1914237049522HLA-C08:02WSDEPIKECDL10.9153415
LDLR-ASF1Bchr1911218190chr1914237049522HLA-C05:01WSDEPIKECDL10.8742415
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B44:13KECDLEWKIIY0.99820.87131021
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B44:07KECDLEWKIIY0.99820.87131021
LDLR-ASF1Bchr1911218190chr1914237049522HLA-B44:26KECDLEWKIIY0.99820.87131021

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Potential FusionNeoAntigen Information of LDLR-ASF1B 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 LDLR-ASF1B

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
1075DEPIKECDLEWKIILDLRASF1Bchr1911218190chr1914237049522

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LDLR-ASF1B

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-B14:023BVN1075DEPIKECDLEWKII-7.4838-7.5956
HLA-B14:023BVN1075DEPIKECDLEWKII-3.16066-4.20376
HLA-B52:013W391075DEPIKECDLEWKII-6.93679-7.04859
HLA-B52:013W391075DEPIKECDLEWKII-6.10064-7.14374
HLA-A11:014UQ21075DEPIKECDLEWKII-7.21307-7.32487
HLA-A24:025HGA1075DEPIKECDLEWKII-6.56769-6.67949
HLA-A24:025HGA1075DEPIKECDLEWKII-4.65311-5.69621
HLA-B44:053DX81075DEPIKECDLEWKII-6.68002-6.79182
HLA-B44:053DX81075DEPIKECDLEWKII-3.22493-4.26803

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Vaccine Design for the FusionNeoAntigens of LDLR-ASF1B

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
LDLR-ASF1Bchr1911218190chr19142370491019KECDLEWKIAAGAGTGCGACCTGGAGTGGAAGATCA
LDLR-ASF1Bchr1911218190chr19142370491021KECDLEWKIIYAAGAGTGCGACCTGGAGTGGAAGATCATTTATG
LDLR-ASF1Bchr1911218190chr1914237049415WSDEPIKECDLGGTCAGATGAACCCATCAAAGAGTGCGACCTGG

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 LDLR-ASF1B

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
STADLDLR-ASF1Bchr1911218190ENST00000455727chr1914237049ENST00000263382TCGA-HU-A4GP

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Potential target of CAR-T therapy development for LDLR-ASF1B

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 LDLR-ASF1B

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 LDLR-ASF1B

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