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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:ITPR3-HDLBP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ITPR3-HDLBP
FusionPDB ID: 40718
FusionGDB2.0 ID: 40718
HgeneTgene
Gene symbol

ITPR3

HDLBP

Gene ID

3710

3069

Gene nameinositol 1,4,5-trisphosphate receptor type 3high density lipoprotein binding protein
SynonymsIP3R|IP3R3HBP|PRO2900|VGL
Cytomap

6p21.31

2q37.3

Type of geneprotein-codingprotein-coding
Descriptioninositol 1,4,5-trisphosphate receptor type 3IP3 receptorinositol 1,4,5-triphosphate receptor, type 3insP3R3type 3 InsP3 receptorvigilinHDL-binding protein
Modification date2020031320200313
UniProtAcc

Q14573

Main function of 5'-partner protein: FUNCTION: Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium.

Q00341

Main function of 5'-partner protein: FUNCTION: Appears to play a role in cell sterol metabolism. It may function to protect cells from over-accumulation of cholesterol.
Ensembl transtripts involved in fusion geneENST idsENST00000374316, ENST00000605930, 
ENST00000476807, ENST00000310931, 
ENST00000391975, ENST00000391976, 
ENST00000427183, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 13 X 8=145628 X 24 X 13=8736
# samples 1529
** MAII scorelog2(15/1456*10)=-3.27897594970282
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(29/8736*10)=-4.91284805090492
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ITPR3 [Title/Abstract] AND HDLBP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ITPR3 [Title/Abstract] AND HDLBP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ITPR3(33659705)-HDLBP(242194573), # samples:1
Anticipated loss of major functional domain due to fusion event.ITPR3-HDLBP 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.
ITPR3-HDLBP 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.
ITPR3-HDLBP 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.
ITPR3-HDLBP 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
HgeneITPR3

GO:0051592

response to calcium ion

19052258



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/chr6:33659705/chr2:242194573)
- 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 ITPR3 (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 HDLBP (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)
ENST00000374316ITPR3chr633659705+ENST00000391976HDLBPchr2242194573-1163485181060112443394
ENST00000374316ITPR3chr633659705+ENST00000310931HDLBPchr2242194573-1163485181060112443394
ENST00000374316ITPR3chr633659705+ENST00000391975HDLBPchr2242194573-1358285181060112443394
ENST00000374316ITPR3chr633659705+ENST00000427183HDLBPchr2242194573-1162485181060112443394
ENST00000605930ITPR3chr633659705+ENST00000391976HDLBPchr2242194573-107937677219104033394
ENST00000605930ITPR3chr633659705+ENST00000310931HDLBPchr2242194573-107937677219104033394
ENST00000605930ITPR3chr633659705+ENST00000391975HDLBPchr2242194573-127417677219104033394
ENST00000605930ITPR3chr633659705+ENST00000427183HDLBPchr2242194573-107837677219104033394

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
ENST00000374316ENST00000391976ITPR3chr633659705+HDLBPchr2242194573-0.0141358390.9858642
ENST00000374316ENST00000310931ITPR3chr633659705+HDLBPchr2242194573-0.0141358390.9858642
ENST00000374316ENST00000391975ITPR3chr633659705+HDLBPchr2242194573-0.0101840820.98981595
ENST00000374316ENST00000427183ITPR3chr633659705+HDLBPchr2242194573-0.0141754970.98582447
ENST00000605930ENST00000391976ITPR3chr633659705+HDLBPchr2242194573-0.0081214920.9918785
ENST00000605930ENST00000310931ITPR3chr633659705+HDLBPchr2242194573-0.0081214920.9918785
ENST00000605930ENST00000391975ITPR3chr633659705+HDLBPchr2242194573-0.0053714560.9946286
ENST00000605930ENST00000427183ITPR3chr633659705+HDLBPchr2242194573-0.0081689270.9918311

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 ITPR3-HDLBP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ITPR3chr633659705HDLBPchr224219457376772486GGVGDILRKPSKDANSFTVSSVAAPS
ITPR3chr633659705HDLBPchr224219457385182486GGVGDILRKPSKDANSFTVSSVAAPS

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Potential FusionNeoAntigen Information of ITPR3-HDLBP 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.
ITPR3-HDLBP_33659705_242194573.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)
ITPR3-HDLBPchr633659705chr22421945738518HLA-B39:06SKDANSFTV0.99720.68051019
ITPR3-HDLBPchr633659705chr22421945738518HLA-B39:01SKDANSFTV0.99130.80071019
ITPR3-HDLBPchr633659705chr22421945738518HLA-B38:01SKDANSFTV0.95920.93541019
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:08KPSKDANSF0.91060.724817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:01KPSKDANSF0.89220.7962817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:03KPSKDANSF0.58770.838817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:02KPSKDANSF0.20390.8925817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:04KPSKDANSF0.20390.8925817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B15:03RKPSKDANSF0.94240.7266717
ITPR3-HDLBPchr633659705chr22421945738518HLA-B07:02RKPSKDANSF0.87850.5722717
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:08RKPSKDANSF0.78550.8503717
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:08LRKPSKDANSF0.97940.8596617
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:01LRKPSKDANSF0.97540.8147617
ITPR3-HDLBPchr633659705chr22421945738518HLA-B39:05SKDANSFTV0.92560.7761019
ITPR3-HDLBPchr633659705chr22421945738518HLA-B39:08SKDANSFTV0.59540.69171019
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:12KPSKDANSF0.20390.8925817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B39:10KPSKDANSF0.07440.8598817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B07:12RKPSKDANSF0.95660.7102717
ITPR3-HDLBPchr633659705chr22421945738518HLA-B39:02SKDANSFTV0.99630.77931019
ITPR3-HDLBPchr633659705chr22421945738518HLA-B38:05SKDANSFTV0.95920.93541019
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:77KPSKDANSF0.89220.7962817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:23KPSKDANSF0.88350.7595817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:20KPSKDANSF0.87460.8382817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:11KPSKDANSF0.81330.8199817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:17KPSKDANSF0.78760.6238817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:30KPSKDANSF0.78760.6238817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:24KPSKDANSF0.62130.7533817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B39:11SKDANSFTV0.56660.61991019
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:13KPSKDANSF0.54790.8444817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:09KPSKDANSF0.20390.8925817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:43KPSKDANSF0.11790.7808817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B15:08KPSKDANSF0.10910.7734817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B15:11KPSKDANSF0.09910.7885817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B67:01KPSKDANSF0.09560.6907817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B18:07KPSKDANSF0.04410.736817
ITPR3-HDLBPchr633659705chr22421945738518HLA-B15:68RKPSKDANSF0.97570.6786717
ITPR3-HDLBPchr633659705chr22421945738518HLA-B15:54RKPSKDANSF0.95740.8662717
ITPR3-HDLBPchr633659705chr22421945738518HLA-B07:09RKPSKDANSF0.90510.562717
ITPR3-HDLBPchr633659705chr22421945738518HLA-B07:22RKPSKDANSF0.87850.5722717
ITPR3-HDLBPchr633659705chr22421945738518HLA-B15:68LRKPSKDANSF0.9990.6316617
ITPR3-HDLBPchr633659705chr22421945738518HLA-B35:77LRKPSKDANSF0.97540.8147617

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Potential FusionNeoAntigen Information of ITPR3-HDLBP 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.
ITPR3-HDLBP_33659705_242194573.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)
ITPR3-HDLBPchr633659705chr22421945738518DRB1-0437VGDILRKPSKDANSF217
ITPR3-HDLBPchr633659705chr22421945738518DRB1-0437GVGDILRKPSKDANS116

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Fusion breakpoint peptide structures of ITPR3-HDLBP

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
5533LRKPSKDANSFTVSITPR3HDLBPchr633659705chr22421945738518

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ITPR3-HDLBP

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-B14:023BVN5533LRKPSKDANSFTVS-5.97758-6.09098
HLA-B14:023BVN5533LRKPSKDANSFTVS-5.15013-6.18543
HLA-B52:013W395533LRKPSKDANSFTVS-6.29935-6.41275
HLA-B52:013W395533LRKPSKDANSFTVS-6.07479-7.11009
HLA-A24:025HGA5533LRKPSKDANSFTVS-7.25246-8.28776
HLA-A24:025HGA5533LRKPSKDANSFTVS-6.23064-6.34404
HLA-B44:053DX85533LRKPSKDANSFTVS-4.66421-5.69951
HLA-B44:053DX85533LRKPSKDANSFTVS-4.52141-4.63481
HLA-A02:016TDR5533LRKPSKDANSFTVS-7.72945-7.84285

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Vaccine Design for the FusionNeoAntigens of ITPR3-HDLBP

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
ITPR3-HDLBPchr633659705chr22421945731019SKDANSFTVTCCAAAGATGCCAATAGCTTCACCGTC
ITPR3-HDLBPchr633659705chr2242194573617LRKPSKDANSFCTCCGCAAGCCCTCCAAAGATGCCAATAGCTTC
ITPR3-HDLBPchr633659705chr2242194573717RKPSKDANSFCGCAAGCCCTCCAAAGATGCCAATAGCTTC
ITPR3-HDLBPchr633659705chr2242194573817KPSKDANSFAAGCCCTCCAAAGATGCCAATAGCTTC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ITPR3-HDLBPchr633659705chr2242194573116GVGDILRKPSKDANSGGCGTGGGCGACATTCTCCGCAAGCCCTCCAAAGATGCCAATAGC
ITPR3-HDLBPchr633659705chr2242194573217VGDILRKPSKDANSFGTGGGCGACATTCTCCGCAAGCCCTCCAAAGATGCCAATAGCTTC

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Information of the samples that have these potential fusion neoantigens of ITPR3-HDLBP

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
Non-CancerITPR3-HDLBPchr633659705ENST00000374316chr2242194573ENST0000031093143N

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Potential target of CAR-T therapy development for ITPR3-HDLBP

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
HgeneITPR3chr6:33659705chr2:242194573ENST00000374316+55592203_222324862672.0TransmembraneHelical
HgeneITPR3chr6:33659705chr2:242194573ENST00000374316+55592236_225624862672.0TransmembraneHelical
HgeneITPR3chr6:33659705chr2:242194573ENST00000374316+55592265_228524862672.0TransmembraneHelical
HgeneITPR3chr6:33659705chr2:242194573ENST00000374316+55592326_234624862672.0TransmembraneHelical
HgeneITPR3chr6:33659705chr2:242194573ENST00000374316+55592369_238924862672.0TransmembraneHelical
HgeneITPR3chr6:33659705chr2:242194573ENST00000605930+54582203_222324862672.0TransmembraneHelical
HgeneITPR3chr6:33659705chr2:242194573ENST00000605930+54582236_225624862672.0TransmembraneHelical
HgeneITPR3chr6:33659705chr2:242194573ENST00000605930+54582265_228524862672.0TransmembraneHelical
HgeneITPR3chr6:33659705chr2:242194573ENST00000605930+54582326_234624862672.0TransmembraneHelical
HgeneITPR3chr6:33659705chr2:242194573ENST00000605930+54582369_238924862672.0TransmembraneHelical

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 ITPR3-HDLBP

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 ITPR3-HDLBP

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