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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:JAG1-INPP5A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: JAG1-INPP5A
FusionPDB ID: 40823
FusionGDB2.0 ID: 40823
HgeneTgene
Gene symbol

JAG1

INPP5A

Gene ID

182

3632

Gene namejagged canonical Notch ligand 1inositol polyphosphate-5-phosphatase A
SynonymsAGS|AGS1|AHD|AWS|CD339|DCHE|HJ1|JAGL15PTASE
Cytomap

20p12.2

10q26.3

Type of geneprotein-codingprotein-coding
Descriptionprotein jagged-1inositol polyphosphate-5-phosphatase A43 kDa inositol polyphosphate 5-phophatase43 kDa inositol polyphosphate 5-phosphataseCTCL tumor antigen HD-CL-02InsP3 5-phosphataseinositol polyphosphate-5-phosphatase, 40kDinositol polyphosphate-5-phosphatase,
Modification date2020031320200313
UniProtAcc

P78504

Main function of 5'-partner protein: FUNCTION: Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation (By similarity). Enhances fibroblast growth factor-induced angiogenesis (in vitro). {ECO:0000250, ECO:0000269|PubMed:18660822, ECO:0000269|PubMed:20437614, ECO:0000269|PubMed:9462510}.

Q14642

Main function of 5'-partner protein: FUNCTION: Phosphatase that specifically hydrolyzes the 5-phosphate of inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate, and inositol 1,3,4,5-tetrasphosphate to inositol 1,3,4-trisphosphate (PubMed:8013665, PubMed:8769125, PubMed:8626616). Plays a crucial role in the survival of cerebellar Purkinje cells (By similarity). {ECO:0000250|UniProtKB:Q7TNC9, ECO:0000269|PubMed:8013665, ECO:0000269|PubMed:8626616, ECO:0000269|PubMed:8769125}.
Ensembl transtripts involved in fusion geneENST idsENST00000254958, ENST00000423891, 
ENST00000488480, 
ENST00000487614, 
ENST00000368593, ENST00000368594, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 7 X 5=2458 X 8 X 3=192
# samples 78
** MAII scorelog2(7/245*10)=-1.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/192*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: JAG1 [Title/Abstract] AND INPP5A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: JAG1 [Title/Abstract] AND INPP5A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)JAG1(10653348)-INPP5A(134421418), # samples:1
Anticipated loss of major functional domain due to fusion event.JAG1-INPP5A 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.
JAG1-INPP5A 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
HgeneJAG1

GO:0001953

negative regulation of cell-matrix adhesion

11549580

HgeneJAG1

GO:0022408

negative regulation of cell-cell adhesion

11549580

HgeneJAG1

GO:0030336

negative regulation of cell migration

11549580

TgeneINPP5A

GO:0046855

inositol phosphate dephosphorylation

8006039



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/chr20:10653348/chr10:134421418)
- 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 JAG1 (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 INPP5A (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)
ENST00000254958JAG1chr2010653348-ENST00000368594INPP5Achr10134421418+35139035162066516
ENST00000254958JAG1chr2010653348-ENST00000368593INPP5Achr10134421418+20129035161991491

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
ENST00000254958ENST00000368594JAG1chr2010653348-INPP5Achr10134421418+0.0005469790.999453
ENST00000254958ENST00000368593JAG1chr2010653348-INPP5Achr10134421418+0.0024006290.9975994

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 JAG1-INPP5A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
JAG1chr2010653348INPP5Achr10134421418903129RNRIVLPFSFAWPPENLQKNWLREFY

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Potential FusionNeoAntigen Information of JAG1-INPP5A 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.
JAG1-INPP5A_10653348_134421418.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)
JAG1-INPP5Achr2010653348chr10134421418903HLA-B51:02FAWPPENL0.99950.68917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B51:01FAWPPENL0.99730.7195917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B56:01LPFSFAWPP0.97280.6898514
JAG1-INPP5Achr2010653348chr10134421418903HLA-A24:14SFAWPPENL0.8120.5355817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:19FAWPPENL10.9963917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:07FAWPPENL10.9926917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:08FAWPPENL10.927917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C15:06FAWPPENL0.99990.9715917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C04:06FAWPPENL0.99980.9494917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C08:04FAWPPENL0.99940.9922917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C08:13FAWPPENL0.99940.9922917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C12:12FAWPPENL0.99820.98917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:14FAWPPENL0.99720.9942917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C08:03FAWPPENL0.99060.9956917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C02:06FAWPPENL0.9660.9932917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B54:01LPFSFAWPP0.99540.7062514
JAG1-INPP5Achr2010653348chr10134421418903HLA-C07:29SFAWPPENL0.55560.9733817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C07:13SFAWPPENL0.49960.9705817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C07:10SFAWPPENL0.43510.9872817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C07:80SFAWPPENL0.40030.9825817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C07:67SFAWPPENL0.40030.9825817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C04:14SFAWPPENL0.39070.9492817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C07:19SFAWPPENL0.3780.9151817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C04:10SFAWPPENL0.10250.9161817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C04:07SFAWPPENL0.0940.9063817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C01:17SFAWPPENL0.07030.9591817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:08FSFAWPPENL0.99960.941717
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:03FAWPPENL10.9953917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:02FAWPPENL10.9871917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:04FAWPPENL10.9953917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:17FAWPPENL10.9841917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:67FAWPPENL0.99990.9927917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:05FAWPPENL0.99990.9641917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:06FAWPPENL0.99960.9964917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C12:03FAWPPENL0.99940.9913917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C12:02FAWPPENL0.99930.9888917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C16:04FAWPPENL0.99930.9929917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C16:01FAWPPENL0.99830.9843917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B51:13FAWPPENL0.99760.5195917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C08:01FAWPPENL0.99060.9956917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B51:14FAWPPENL0.98970.6046917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B51:21FAWPPENL0.98790.7146917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B51:09FAWPPENL0.98410.7074917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B35:13FAWPPENL0.98350.9652917
JAG1-INPP5Achr2010653348chr10134421418903HLA-C17:01FAWPPENL0.97130.9498917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B51:06FAWPPENL0.96840.6734917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B07:13FAWPPENL0.74030.8466917
JAG1-INPP5Achr2010653348chr10134421418903HLA-B55:02LPFSFAWPP0.95140.6567514
JAG1-INPP5Achr2010653348chr10134421418903HLA-C03:67SFAWPPENL0.57750.9951817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C07:02SFAWPPENL0.40030.9825817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C04:04SFAWPPENL0.2480.9442817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C07:04SFAWPPENL0.21580.9465817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C06:06SFAWPPENL0.21290.9926817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C14:02SFAWPPENL0.16860.9729817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C14:03SFAWPPENL0.16860.9729817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C04:01SFAWPPENL0.0940.9063817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C18:01SFAWPPENL0.08910.9125817
JAG1-INPP5Achr2010653348chr10134421418903HLA-C01:02SFAWPPENL0.05510.9569817

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Potential FusionNeoAntigen Information of JAG1-INPP5A 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 JAG1-INPP5A

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
6627PFSFAWPPENLQKNJAG1INPP5Achr2010653348chr10134421418903

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of JAG1-INPP5A

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-B14:023BVN6627PFSFAWPPENLQKN-7.32363-7.43703
HLA-B14:023BVN6627PFSFAWPPENLQKN-2.91635-3.95165
HLA-B52:013W396627PFSFAWPPENLQKN-7.01993-8.05523
HLA-B52:013W396627PFSFAWPPENLQKN-6.14811-6.26151
HLA-A11:014UQ26627PFSFAWPPENLQKN-4.65881-4.77221
HLA-A24:025HGA6627PFSFAWPPENLQKN-6.9585-7.0719
HLA-A24:025HGA6627PFSFAWPPENLQKN-6.22358-7.25888
HLA-B44:053DX86627PFSFAWPPENLQKN-7.18833-7.30173
HLA-B44:053DX86627PFSFAWPPENLQKN-3.48335-4.51865
HLA-A02:016TDR6627PFSFAWPPENLQKN-5.74716-5.86056

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Vaccine Design for the FusionNeoAntigens of JAG1-INPP5A

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
JAG1-INPP5Achr2010653348chr10134421418514LPFSFAWPPCTGCCTTTCAGTTTCGCCTGGCCGCCA
JAG1-INPP5Achr2010653348chr10134421418717FSFAWPPENLTTCAGTTTCGCCTGGCCGCCAGAAAACCTG
JAG1-INPP5Achr2010653348chr10134421418817SFAWPPENLAGTTTCGCCTGGCCGCCAGAAAACCTG
JAG1-INPP5Achr2010653348chr10134421418917FAWPPENLTTCGCCTGGCCGCCAGAAAACCTG

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 JAG1-INPP5A

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
COADJAG1-INPP5Achr2010653348ENST00000254958chr10134421418ENST00000368593TCGA-A6-2685

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Potential target of CAR-T therapy development for JAG1-INPP5A

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 JAG1-INPP5A

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 JAG1-INPP5A

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