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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:PARD3-HTRA1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PARD3-HTRA1
FusionPDB ID: 62708
FusionGDB2.0 ID: 62708
HgeneTgene
Gene symbol

PARD3

HTRA1

Gene ID

56288

5654

Gene namepar-3 family cell polarity regulatorHtrA serine peptidase 1
SynonymsASIP|Baz|PAR3|PAR3alpha|PARD-3|PARD3A|PPP1R118|SE2-5L16|SE2-5LT1|SE2-5T2ARMD7|CADASIL2|CARASIL|HtrA|L56|ORF480|PRSS11
Cytomap

10p11.22-p11.21

10q26.13

Type of geneprotein-codingprotein-coding
Descriptionpartitioning defective 3 homologCTCL tumor antigen se2-5PAR3-alphaatypical PKC isotype-specific interacting proteinbazookapar-3 family cell polarity regulator alphapar-3 partitioning defective 3 homologprotein phosphatase 1, regulatory subunit 118serine protease HTRA1IGFBP5-proteasehigh-temperature requirement A serine peptidase 1protease, serine, 11 (IGF binding)
Modification date2020032720200322
UniProtAcc.

Q92743

Main function of 5'-partner protein: FUNCTION: Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, although it is unclear whether TGF-beta proteins are themselves degraded. By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets. {ECO:0000269|PubMed:16377621, ECO:0000269|PubMed:20671064, ECO:0000269|PubMed:9852107}.
Ensembl transtripts involved in fusion geneENST idsENST00000466092, ENST00000544292, 
ENST00000340077, ENST00000346874, 
ENST00000350537, ENST00000374773, 
ENST00000374776, ENST00000374788, 
ENST00000374789, ENST00000374790, 
ENST00000374794, ENST00000545260, 
ENST00000545693, ENST00000374768, 
ENST00000368984, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score33 X 20 X 14=92404 X 5 X 4=80
# samples 495
** MAII scorelog2(49/9240*10)=-4.23703919730085
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PARD3 [Title/Abstract] AND HTRA1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PARD3 [Title/Abstract] AND HTRA1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PARD3(34620045)-HTRA1(124248418), # samples:1
Anticipated loss of major functional domain due to fusion event.PARD3-HTRA1 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.
PARD3-HTRA1 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.
PARD3-HTRA1 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.
PARD3-HTRA1 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.
PARD3-HTRA1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PARD3-HTRA1 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted 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/chr10:34620045/chr10:124248418)
- 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 PARD3 (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 HTRA1 (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)
ENST00000545260PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4422290219838721224
ENST00000545693PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4644312419840941298
ENST00000350537PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4550303019440001268
ENST00000346874PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4688316819441381314
ENST00000374789PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4688316819441381314
ENST00000374790PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4508298819439581254
ENST00000374794PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4463294319439131239
ENST00000374788PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4679315919441291311
ENST00000374776PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4550303019440001268
ENST00000340077PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4683316319841331311
ENST00000374773PARD3chr1034620045-ENST00000368984HTRA1chr10124248418+4589306919440391281

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
ENST00000545260ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0016074040.9983925
ENST00000545693ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0015035810.9984964
ENST00000350537ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0014372760.99856275
ENST00000346874ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0015807660.9984193
ENST00000374789ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0015807660.9984193
ENST00000374790ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0015947610.9984053
ENST00000374794ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0012658220.9987342
ENST00000374788ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0019236080.99807644
ENST00000374776ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0014372760.99856275
ENST00000340077ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.001911380.99808854
ENST00000374773ENST00000368984PARD3chr1034620045-HTRA1chr10124248418+0.0012911250.99870884

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 PARD3-HTRA1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PARD3chr1034620045HTRA1chr101242484182902902PAVDDDDEGMETWQEDPNSLRHKYNF
PARD3chr1034620045HTRA1chr101242484182943917PAVDDDDEGMETWQEDPNSLRHKYNF
PARD3chr1034620045HTRA1chr101242484182988932PAVDDDDEGMETWQEDPNSLRHKYNF
PARD3chr1034620045HTRA1chr101242484183030946PAVDDDDEGMETWQEDPNSLRHKYNF
PARD3chr1034620045HTRA1chr101242484183069959PAVDDDDEGMETWQEDPNSLRHKYNF
PARD3chr1034620045HTRA1chr101242484183124976PAVDDDDEGMETWQEDPNSLRHKYNF
PARD3chr1034620045HTRA1chr101242484183159989PAVDDDDEGMETWQEDPNSLRHKYNF
PARD3chr1034620045HTRA1chr101242484183163989PAVDDDDEGMETWQEDPNSLRHKYNF
PARD3chr1034620045HTRA1chr101242484183168992PAVDDDDEGMETWQEDPNSLRHKYNF

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Potential FusionNeoAntigen Information of PARD3-HTRA1 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.
PARD3-HTRA1_34620045_124248418.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)
PARD3-HTRA1chr1034620045chr101242484183163HLA-B39:13WQEDPNSL0.95850.95761220
PARD3-HTRA1chr1034620045chr101242484183163HLA-B39:13METWQEDPNSL0.99440.9112920
PARD3-HTRA1chr1034620045chr101242484183163HLA-B39:05WQEDPNSL0.96020.95431220
PARD3-HTRA1chr1034620045chr101242484183163HLA-B39:08WQEDPNSL0.9550.92131220
PARD3-HTRA1chr1034620045chr101242484183163HLA-C04:10TWQEDPNSL0.90290.85771120
PARD3-HTRA1chr1034620045chr101242484183163HLA-C04:07TWQEDPNSL0.89460.88481120
PARD3-HTRA1chr1034620045chr101242484183163HLA-C04:14TWQEDPNSL0.4590.85521120
PARD3-HTRA1chr1034620045chr101242484183163HLA-C07:13TWQEDPNSL0.40940.94811120
PARD3-HTRA1chr1034620045chr101242484183163HLA-C07:29TWQEDPNSL0.34860.95811120
PARD3-HTRA1chr1034620045chr101242484183163HLA-B39:08METWQEDPNSL0.99530.8808920
PARD3-HTRA1chr1034620045chr101242484183163HLA-B39:02WQEDPNSL0.97920.95671220
PARD3-HTRA1chr1034620045chr101242484183163HLA-B39:11WQEDPNSL0.96350.89391220
PARD3-HTRA1chr1034620045chr101242484183163HLA-B15:09WQEDPNSL0.92110.88771220
PARD3-HTRA1chr1034620045chr101242484183163HLA-C04:01TWQEDPNSL0.89460.88481120
PARD3-HTRA1chr1034620045chr101242484183163HLA-C18:01TWQEDPNSL0.87950.891120
PARD3-HTRA1chr1034620045chr101242484183163HLA-C14:03TWQEDPNSL0.60490.97241120
PARD3-HTRA1chr1034620045chr101242484183163HLA-C14:02TWQEDPNSL0.60490.97241120
PARD3-HTRA1chr1034620045chr101242484183163HLA-C07:04TWQEDPNSL0.42920.95761120
PARD3-HTRA1chr1034620045chr101242484183163HLA-C04:04TWQEDPNSL0.36640.84761120
PARD3-HTRA1chr1034620045chr101242484183163HLA-A69:01ETWQEDPNSL0.83620.56931020
PARD3-HTRA1chr1034620045chr101242484183163HLA-B40:04METWQEDPNSL0.99960.7208920
PARD3-HTRA1chr1034620045chr101242484183163HLA-B41:03METWQEDPNSL0.98090.7571920

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Potential FusionNeoAntigen Information of PARD3-HTRA1 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.
PARD3-HTRA1_34620045_124248418.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)
PARD3-HTRA1chr1034620045chr101242484183163DRB1-0305METWQEDPNSLRHKY924
PARD3-HTRA1chr1034620045chr101242484183163DRB1-0305GMETWQEDPNSLRHK823
PARD3-HTRA1chr1034620045chr101242484183163DRB1-0305ETWQEDPNSLRHKYN1025
PARD3-HTRA1chr1034620045chr101242484183163DRB1-0340METWQEDPNSLRHKY924

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Fusion breakpoint peptide structures of PARD3-HTRA1

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
1059DEGMETWQEDPNSLPARD3HTRA1chr1034620045chr101242484183163

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PARD3-HTRA1

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-B14:023BVN1059DEGMETWQEDPNSL-7.15543-7.26883
HLA-B14:023BVN1059DEGMETWQEDPNSL-4.77435-5.80965
HLA-B52:013W391059DEGMETWQEDPNSL-6.80875-6.92215
HLA-B52:013W391059DEGMETWQEDPNSL-4.20386-5.23916
HLA-A11:014UQ21059DEGMETWQEDPNSL-7.5194-8.5547
HLA-A11:014UQ21059DEGMETWQEDPNSL-6.9601-7.0735
HLA-A24:025HGA1059DEGMETWQEDPNSL-7.52403-7.63743
HLA-A24:025HGA1059DEGMETWQEDPNSL-5.82433-6.85963
HLA-B27:056PYJ1059DEGMETWQEDPNSL-3.28285-4.31815
HLA-B44:053DX81059DEGMETWQEDPNSL-5.91172-6.94702
HLA-B44:053DX81059DEGMETWQEDPNSL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PARD3-HTRA1

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
PARD3-HTRA1chr1034620045chr101242484181020ETWQEDPNSLTGGAGACCTGGCAGGAAGATCCCAACAGTT
PARD3-HTRA1chr1034620045chr101242484181120TWQEDPNSLAGACCTGGCAGGAAGATCCCAACAGTT
PARD3-HTRA1chr1034620045chr101242484181220WQEDPNSLCCTGGCAGGAAGATCCCAACAGTT
PARD3-HTRA1chr1034620045chr10124248418920METWQEDPNSLGCATGGAGACCTGGCAGGAAGATCCCAACAGTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PARD3-HTRA1chr1034620045chr101242484181025ETWQEDPNSLRHKYNTGGAGACCTGGCAGGAAGATCCCAACAGTTTGCGCCATAAATATA
PARD3-HTRA1chr1034620045chr10124248418823GMETWQEDPNSLRHKAAGGCATGGAGACCTGGCAGGAAGATCCCAACAGTTTGCGCCATA
PARD3-HTRA1chr1034620045chr10124248418924METWQEDPNSLRHKYGCATGGAGACCTGGCAGGAAGATCCCAACAGTTTGCGCCATAAAT

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Information of the samples that have these potential fusion neoantigens of PARD3-HTRA1

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
HNSCPARD3-HTRA1chr1034620045ENST00000340077chr10124248418ENST00000368984TCGA-CV-6953-01A

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Potential target of CAR-T therapy development for PARD3-HTRA1

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 PARD3-HTRA1

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 PARD3-HTRA1

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