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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:LRP5-HSCB

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LRP5-HSCB
FusionPDB ID: 49797
FusionGDB2.0 ID: 49797
HgeneTgene
Gene symbol

LRP5

HSCB

Gene ID

4041

150274

Gene nameLDL receptor related protein 5HscB mitochondrial iron-sulfur cluster cochaperone
SynonymsBMND1|EVR1|EVR4|HBM|LR3|LRP-5|LRP-7|LRP7|OPPG|OPS|OPTA1|PCLD4|VBCH2DNAJC20|HSC20|JAC1
Cytomap

11q13.2

22q12.1

Type of geneprotein-codingprotein-coding
Descriptionlow-density lipoprotein receptor-related protein 5low density lipoprotein receptor-related protein 5low density lipoprotein receptor-related protein 7iron-sulfur cluster co-chaperone protein HscBDnaJ (Hsp40) homolog, subfamily C, member 20HscB iron-sulfur cluster co-chaperone homologHscB mitochondrial iron-sulfur cluster co-chaperoneJ-type co-chaperone HSC20epididymis secretory sperm binding prote
Modification date2020032920200320
UniProtAcc

A4QPB2

Main function of 5'-partner protein:

Q8IWL3

Main function of 5'-partner protein: FUNCTION: Acts as a co-chaperone in iron-sulfur cluster assembly in both mitochondria and the cytoplasm (PubMed:20668094, PubMed:29309586). Required for incorporation of iron-sulfur clusters into SDHB, the iron-sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain (PubMed:26749241). Recruited to SDHB by interaction with SDHAF1 which first binds SDHB and then recruits the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20 (PubMed:26749241). Also mediates complex formation between components of the cytosolic iron-sulfur biogenesis pathway and the CIA targeting complex composed of CIAO1, DIPK1B/FAM69B and MMS19 by binding directly to the scaffold protein ISCU and to CIAO1 (PubMed:29309586). This facilitates iron-sulfur cluster insertion into a number of cytoplasmic and nuclear proteins including POLD1, ELP3, DPYD and PPAT (PubMed:29309586). {ECO:0000269|PubMed:20668094, ECO:0000269|PubMed:26749241, ECO:0000269|PubMed:29309586}.
Ensembl transtripts involved in fusion geneENST idsENST00000294304, ENST00000529481, 
ENST00000495977, ENST00000216027, 
ENST00000398941, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score36 X 25 X 12=1080012 X 9 X 8=864
# samples 4118
** MAII scorelog2(41/10800*10)=-4.71926359243275
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(18/864*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LRP5 [Title/Abstract] AND HSCB [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LRP5 [Title/Abstract] AND HSCB [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LRP5(68214001)-HSCB(29139870), # samples:1
Anticipated loss of major functional domain due to fusion event.LRP5-HSCB 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.
LRP5-HSCB 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.
LRP5-HSCB 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.
LRP5-HSCB 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
HgeneLRP5

GO:0008284

positive regulation of cell proliferation

9790987

HgeneLRP5

GO:0045840

positive regulation of mitotic nuclear division

9790987

HgeneLRP5

GO:0045893

positive regulation of transcription, DNA-templated

15035989|17955262

HgeneLRP5

GO:0045944

positive regulation of transcription by RNA polymerase II

12857724

HgeneLRP5

GO:0060070

canonical Wnt signaling pathway

11029007|12121999|12857724|15908424|24706814|25920554



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/chr11:68214001/chr22:29139870)
- 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 LRP5 (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 HSCB (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)
ENST00000294304LRP5chr1168214001+ENST00000216027HSCBchr2229139870+5505469210651631685
ENST00000294304LRP5chr1168214001+ENST00000398941HSCBchr2229139870+5370469210648871593

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
ENST00000294304ENST00000216027LRP5chr1168214001+HSCBchr2229139870+0.0009900360.99900997
ENST00000294304ENST00000398941LRP5chr1168214001+HSCBchr2229139870+0.0019967760.9980032

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 LRP5-HSCB

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LRP5chr1168214001HSCBchr222913987046921526DMFYSSNIPATARPYSNRSFRVDTAK

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Potential FusionNeoAntigen Information of LRP5-HSCB 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.
LRP5-HSCB_68214001_29139870.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)
LRP5-HSCBchr1168214001chr22291398704692HLA-A30:08ATARPYSNR0.98250.7565918
LRP5-HSCBchr1168214001chr22291398704692HLA-B15:02NIPATARPY0.91680.7774615
LRP5-HSCBchr1168214001chr22291398704692HLA-B57:03ATARPYSNRSF0.99820.9308920
LRP5-HSCBchr1168214001chr22291398704692HLA-B07:12RPYSNRSF0.9960.54421220
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:95ARPYSNRSF0.970.65311120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:05ARPYSNRSF0.95210.96211120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:27ARPYSNRSF0.90220.9411120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:29ARPYSNRSF0.84720.93951120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:46ARPYSNRSF0.83790.80761120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:19ARPYSNRSF0.83570.59371120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:80ARPYSNRSF0.79580.91061120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:67ARPYSNRSF0.79580.91061120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:10ARPYSNRSF0.77460.93221120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:13ARPYSNRSF0.65790.88581120
LRP5-HSCBchr1168214001chr22291398704692HLA-C12:16ARPYSNRSF0.07160.94731120
LRP5-HSCBchr1168214001chr22291398704692HLA-C12:12TARPYSNRSF0.99710.9091020
LRP5-HSCBchr1168214001chr22291398704692HLA-B35:30IPATARPY0.99540.5368715
LRP5-HSCBchr1168214001chr22291398704692HLA-B35:17IPATARPY0.99540.5368715
LRP5-HSCBchr1168214001chr22291398704692HLA-B35:11IPATARPY0.99340.6925715
LRP5-HSCBchr1168214001chr22291398704692HLA-B35:24IPATARPY0.99250.8323715
LRP5-HSCBchr1168214001chr22291398704692HLA-B15:11IPATARPY0.97820.7116715
LRP5-HSCBchr1168214001chr22291398704692HLA-B35:43IPATARPY0.97090.7136715
LRP5-HSCBchr1168214001chr22291398704692HLA-B18:07IPATARPY0.88610.7986715
LRP5-HSCBchr1168214001chr22291398704692HLA-B27:06ARPYSNRSF0.99750.74551120
LRP5-HSCBchr1168214001chr22291398704692HLA-A30:01ATARPYSNR0.98380.904918
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:01ARPYSNRSF0.97860.61481120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:17ARPYSNRSF0.8710.96181120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:02ARPYSNRSF0.79580.91061120
LRP5-HSCBchr1168214001chr22291398704692HLA-C07:22ARPYSNRSF0.73350.72821120
LRP5-HSCBchr1168214001chr22291398704692HLA-C06:08ARPYSNRSF0.64460.98161120
LRP5-HSCBchr1168214001chr22291398704692HLA-C03:67ARPYSNRSF0.32380.96651120
LRP5-HSCBchr1168214001chr22291398704692HLA-C06:06ARPYSNRSF0.2560.98821120
LRP5-HSCBchr1168214001chr22291398704692HLA-B15:68ARPYSNRSF0.10420.55131120
LRP5-HSCBchr1168214001chr22291398704692HLA-C06:17ARPYSNRSF0.03750.98881120
LRP5-HSCBchr1168214001chr22291398704692HLA-C06:02ARPYSNRSF0.03750.98881120
LRP5-HSCBchr1168214001chr22291398704692HLA-B27:10ARPYSNRSFR0.99910.75061121
LRP5-HSCBchr1168214001chr22291398704692HLA-C16:04TARPYSNRSF0.99120.94941020
LRP5-HSCBchr1168214001chr22291398704692HLA-B57:04ATARPYSNRSF0.99970.7482920
LRP5-HSCBchr1168214001chr22291398704692HLA-B57:02ATARPYSNRSF0.99920.8199920

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Potential FusionNeoAntigen Information of LRP5-HSCB 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.
LRP5-HSCB_68214001_29139870.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)
LRP5-HSCBchr1168214001chr22291398704692DRB3-0202DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0202MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0205DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0205MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0209DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0210DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0210MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0211DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0211MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0212DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0212MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0213DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0213MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0214DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0215DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0215MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0216DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0217DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0217MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0218DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0218MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0219DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0219MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0220DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0220MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0221DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0222DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0222MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0223DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0223MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0225DMFYSSNIPATARPY015
LRP5-HSCBchr1168214001chr22291398704692DRB3-0225MFYSSNIPATARPYS116
LRP5-HSCBchr1168214001chr22291398704692DRB3-0303DMFYSSNIPATARPY015

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Fusion breakpoint peptide structures of LRP5-HSCB

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
6208NIPATARPYSNRSFLRP5HSCBchr1168214001chr22291398704692

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LRP5-HSCB

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-B14:023BVN6208NIPATARPYSNRSF-7.08318-7.19658
HLA-B14:023BVN6208NIPATARPYSNRSF-4.62301-5.65831
HLA-B52:013W396208NIPATARPYSNRSF-5.84933-5.96273
HLA-B52:013W396208NIPATARPYSNRSF-5.68495-6.72025
HLA-A11:014UQ26208NIPATARPYSNRSF-10.2752-10.3886
HLA-A11:014UQ26208NIPATARPYSNRSF-1.67984-2.71514
HLA-A24:025HGA6208NIPATARPYSNRSF-7.7437-7.8571
HLA-A24:025HGA6208NIPATARPYSNRSF-5.77832-6.81362
HLA-B27:056PYJ6208NIPATARPYSNRSF-6.77238-6.88578
HLA-B44:053DX86208NIPATARPYSNRSF-5.20192-5.31532
HLA-B44:053DX86208NIPATARPYSNRSF-4.69293-5.72823

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Vaccine Design for the FusionNeoAntigens of LRP5-HSCB

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
LRP5-HSCBchr1168214001chr22291398701020TARPYSNRSFACCGTACAGCAACCGTTCCTTCAGAGTTGA
LRP5-HSCBchr1168214001chr22291398701120ARPYSNRSFGTACAGCAACCGTTCCTTCAGAGTTGA
LRP5-HSCBchr1168214001chr22291398701121ARPYSNRSFRGTACAGCAACCGTTCCTTCAGAGTTGATAC
LRP5-HSCBchr1168214001chr22291398701220RPYSNRSFCAGCAACCGTTCCTTCAGAGTTGA
LRP5-HSCBchr1168214001chr2229139870615NIPATARPYGGCCACTGCGAGACCGTACAGCAACCG
LRP5-HSCBchr1168214001chr2229139870715IPATARPYCACTGCGAGACCGTACAGCAACCG
LRP5-HSCBchr1168214001chr2229139870918ATARPYSNRGAGACCGTACAGCAACCGTTCCTTCAG
LRP5-HSCBchr1168214001chr2229139870920ATARPYSNRSFGAGACCGTACAGCAACCGTTCCTTCAGAGTTGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LRP5-HSCBchr1168214001chr2229139870015DMFYSSNIPATARPYCTACTCTTCAAACATTCCGGCCACTGCGAGACCGTACAGCAACCG
LRP5-HSCBchr1168214001chr2229139870116MFYSSNIPATARPYSCTCTTCAAACATTCCGGCCACTGCGAGACCGTACAGCAACCGTTC

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Information of the samples that have these potential fusion neoantigens of LRP5-HSCB

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
HNSCLRP5-HSCBchr1168214001ENST00000294304chr2229139870ENST00000216027TCGA-CV-6939-01A

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Potential target of CAR-T therapy development for LRP5-HSCB

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
HgeneLRP5chr11:68214001chr22:29139870ENST00000294304+22231385_140715281616.0TransmembraneHelical

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 LRP5-HSCB

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 LRP5-HSCB

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