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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:PVRL3-CASK

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PVRL3-CASK
FusionPDB ID: 70761
FusionGDB2.0 ID: 70761
HgeneTgene
Gene symbol

PVRL3

CASK

Gene ID

25945

8573

Gene namenectin cell adhesion molecule 3calcium/calmodulin dependent serine protein kinase
SynonymsCD113|CDW113|NECTIN-3|PPR3|PRR3|PVRL3|PVRR3CAGH39|CAMGUK|CMG|FGS4|LIN2|MICPCH|MRXSNA|TNRC8|hCASK
Cytomap

3q13.13

Xp11.4

Type of geneprotein-codingprotein-coding
Descriptionnectin-3nectin 3poliovirus receptor-related 3poliovirus receptor-related protein 3peripheral plasma membrane protein CASKcalcium/calmodulin-dependent serin protein kinasecalcium/calmodulin-dependent serine protein kinase (MAGUK family)calcium/calmodulin-dependent serine protein kinase membrane-associated guanylate kinaseprotein lin
Modification date2020031320200327
UniProtAcc.

Q8WXE0

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000319792, ENST00000485303, 
ENST00000493615, ENST00000488016, 
ENST00000378154, ENST00000472704, 
ENST00000318588, ENST00000361962, 
ENST00000378158, ENST00000378163, 
ENST00000378166, ENST00000421587, 
ENST00000442742, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 3=2715 X 14 X 9=1890
# samples 317
** MAII scorelog2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(17/1890*10)=-3.47477958297073
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PVRL3 [Title/Abstract] AND CASK [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PVRL3 [Title/Abstract] AND CASK [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PVRL3(110845182)-CASK(41469278), # samples:1
Anticipated loss of major functional domain due to fusion event.PVRL3-CASK 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.
PVRL3-CASK 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.
PVRL3-CASK 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.
PVRL3-CASK 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
TgeneCASK

GO:0010839

negative regulation of keratinocyte proliferation

18664494



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/chr3:110845182/chrX:41469278)
- 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 PVRL3 (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 CASK (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)
ENST00000493615PVRL3chr3110845182+ENST00000421587CASKchrX41469278-841712522162930904
ENST00000493615PVRL3chr3110845182+ENST00000318588CASKchrX41469278-847112522162984922
ENST00000493615PVRL3chr3110845182+ENST00000361962CASKchrX41469278-843512522162948910
ENST00000493615PVRL3chr3110845182+ENST00000378163CASKchrX41469278-415512522162999927
ENST00000493615PVRL3chr3110845182+ENST00000378158CASKchrX41469278-371612522162948910
ENST00000493615PVRL3chr3110845182+ENST00000378166CASKchrX41469278-331512522162984922
ENST00000493615PVRL3chr3110845182+ENST00000442742CASKchrX41469278-300012522162915899
ENST00000485303PVRL3chr3110845182+ENST00000421587CASKchrX41469278-850913442753022915
ENST00000485303PVRL3chr3110845182+ENST00000318588CASKchrX41469278-856313442753076933
ENST00000485303PVRL3chr3110845182+ENST00000361962CASKchrX41469278-852713442753040921
ENST00000485303PVRL3chr3110845182+ENST00000378163CASKchrX41469278-424713442753091938
ENST00000485303PVRL3chr3110845182+ENST00000378158CASKchrX41469278-380813442753040921
ENST00000485303PVRL3chr3110845182+ENST00000378166CASKchrX41469278-340713442753076933
ENST00000485303PVRL3chr3110845182+ENST00000442742CASKchrX41469278-309213442753007910
ENST00000319792PVRL3chr3110845182+ENST00000421587CASKchrX41469278-838412191502897915
ENST00000319792PVRL3chr3110845182+ENST00000318588CASKchrX41469278-843812191502951933
ENST00000319792PVRL3chr3110845182+ENST00000361962CASKchrX41469278-840212191502915921
ENST00000319792PVRL3chr3110845182+ENST00000378163CASKchrX41469278-412212191502966938
ENST00000319792PVRL3chr3110845182+ENST00000378158CASKchrX41469278-368312191502915921
ENST00000319792PVRL3chr3110845182+ENST00000378166CASKchrX41469278-328212191502951933
ENST00000319792PVRL3chr3110845182+ENST00000442742CASKchrX41469278-296712191502882910

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
ENST00000493615ENST00000421587PVRL3chr3110845182+CASKchrX41469278-0.0001089110.99989104
ENST00000493615ENST00000318588PVRL3chr3110845182+CASKchrX41469278-9.64E-050.99990356
ENST00000493615ENST00000361962PVRL3chr3110845182+CASKchrX41469278-0.0001207280.99987924
ENST00000493615ENST00000378163PVRL3chr3110845182+CASKchrX41469278-0.0001148230.9998852
ENST00000493615ENST00000378158PVRL3chr3110845182+CASKchrX41469278-0.0001618410.9998381
ENST00000493615ENST00000378166PVRL3chr3110845182+CASKchrX41469278-0.000320380.9996797
ENST00000493615ENST00000442742PVRL3chr3110845182+CASKchrX41469278-0.0006573190.9993426
ENST00000485303ENST00000421587PVRL3chr3110845182+CASKchrX41469278-0.0002156870.9997843
ENST00000485303ENST00000318588PVRL3chr3110845182+CASKchrX41469278-0.0001816920.9998184
ENST00000485303ENST00000361962PVRL3chr3110845182+CASKchrX41469278-0.0002130530.9997869
ENST00000485303ENST00000378163PVRL3chr3110845182+CASKchrX41469278-0.0001640160.99983597
ENST00000485303ENST00000378158PVRL3chr3110845182+CASKchrX41469278-0.0002735750.99972636
ENST00000485303ENST00000378166PVRL3chr3110845182+CASKchrX41469278-0.0005213750.99947864
ENST00000485303ENST00000442742PVRL3chr3110845182+CASKchrX41469278-0.0009181790.99908185
ENST00000319792ENST00000421587PVRL3chr3110845182+CASKchrX41469278-0.0002151110.9997849
ENST00000319792ENST00000318588PVRL3chr3110845182+CASKchrX41469278-0.0001816260.9998184
ENST00000319792ENST00000361962PVRL3chr3110845182+CASKchrX41469278-0.000212830.99978715
ENST00000319792ENST00000378163PVRL3chr3110845182+CASKchrX41469278-0.0001650350.9998349
ENST00000319792ENST00000378158PVRL3chr3110845182+CASKchrX41469278-0.0002809640.99971896
ENST00000319792ENST00000378166PVRL3chr3110845182+CASKchrX41469278-0.0005335020.9994665
ENST00000319792ENST00000442742PVRL3chr3110845182+CASKchrX41469278-0.0009584220.9990415

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 PVRL3-CASK

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PVRL3chr3110845182CASKchrX414692781219356LGQRSDQKVIYISGAVSQVLDSLEEI
PVRL3chr3110845182CASKchrX414692781252345LGQRSDQKVIYISGAVSQVLDSLEEI
PVRL3chr3110845182CASKchrX414692781344356LGQRSDQKVIYISGAVSQVLDSLEEI

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Potential FusionNeoAntigen Information of PVRL3-CASK 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.
PVRL3-CASK_110845182_41469278.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)
PVRL3-CASKchr3110845182chrX414692781219HLA-A02:21YISGAVSQV0.99650.58661019
PVRL3-CASKchr3110845182chrX414692781219HLA-A02:38YISGAVSQV0.99530.57491019
PVRL3-CASKchr3110845182chrX414692781219HLA-A02:13YISGAVSQV0.99480.67121019
PVRL3-CASKchr3110845182chrX414692781219HLA-A02:27YISGAVSQV0.99440.50411019
PVRL3-CASKchr3110845182chrX414692781219HLA-A02:04YISGAVSQV0.98980.65241019
PVRL3-CASKchr3110845182chrX414692781219HLA-A02:17YISGAVSQV0.98290.61541019
PVRL3-CASKchr3110845182chrX414692781219HLA-A24:14IYISGAVSQVL0.98850.5332920
PVRL3-CASKchr3110845182chrX414692781219HLA-C03:08ISGAVSQVL0.99970.8791120
PVRL3-CASKchr3110845182chrX414692781219HLA-C03:19ISGAVSQVL0.99960.96871120
PVRL3-CASKchr3110845182chrX414692781219HLA-C03:07ISGAVSQVL0.99960.93071120
PVRL3-CASKchr3110845182chrX414692781219HLA-C15:06ISGAVSQVL0.99910.86181120
PVRL3-CASKchr3110845182chrX414692781219HLA-C12:04YISGAVSQV0.99850.98011019
PVRL3-CASKchr3110845182chrX414692781219HLA-C06:03YISGAVSQV0.99840.98421019
PVRL3-CASKchr3110845182chrX414692781219HLA-C15:06YISGAVSQV0.99760.87541019
PVRL3-CASKchr3110845182chrX414692781219HLA-C04:06YISGAVSQV0.99710.96111019
PVRL3-CASKchr3110845182chrX414692781219HLA-C03:07YISGAVSQV0.99650.95611019
PVRL3-CASKchr3110845182chrX414692781219HLA-C08:13YISGAVSQV0.98510.96841019
PVRL3-CASKchr3110845182chrX414692781219HLA-C08:04YISGAVSQV0.98510.96841019
PVRL3-CASKchr3110845182chrX414692781219HLA-C08:04ISGAVSQVL0.98320.94251120
PVRL3-CASKchr3110845182chrX414692781219HLA-C08:13ISGAVSQVL0.98320.94251120
PVRL3-CASKchr3110845182chrX414692781219HLA-C02:06YISGAVSQV0.8520.9661019
PVRL3-CASKchr3110845182chrX414692781219HLA-C03:04ISGAVSQVL0.99970.96631120
PVRL3-CASKchr3110845182chrX414692781219HLA-C03:03ISGAVSQVL0.99970.96631120
PVRL3-CASKchr3110845182chrX414692781219HLA-C03:05ISGAVSQVL0.99940.87851120
PVRL3-CASKchr3110845182chrX414692781219HLA-C03:17ISGAVSQVL0.99930.94111120
PVRL3-CASKchr3110845182chrX414692781219HLA-C15:05ISGAVSQVL0.99890.88751120
PVRL3-CASKchr3110845182chrX414692781219HLA-C15:02ISGAVSQVL0.99880.82961120
PVRL3-CASKchr3110845182chrX414692781219HLA-C15:02YISGAVSQV0.99830.87511019
PVRL3-CASKchr3110845182chrX414692781219HLA-C15:05YISGAVSQV0.9980.89211019
PVRL3-CASKchr3110845182chrX414692781219HLA-A02:03YISGAVSQV0.99780.58071019
PVRL3-CASKchr3110845182chrX414692781219HLA-A02:14YISGAVSQV0.99650.53291019
PVRL3-CASKchr3110845182chrX414692781219HLA-A02:06YISGAVSQV0.99650.58661019
PVRL3-CASKchr3110845182chrX414692781219HLA-C12:03YISGAVSQV0.99580.9611019
PVRL3-CASKchr3110845182chrX414692781219HLA-C04:03YISGAVSQV0.99510.95251019
PVRL3-CASKchr3110845182chrX414692781219HLA-A68:02YISGAVSQV0.99060.54681019
PVRL3-CASKchr3110845182chrX414692781219HLA-A69:01YISGAVSQV0.98230.69941019
PVRL3-CASKchr3110845182chrX414692781219HLA-C03:06ISGAVSQVL0.97470.96691120
PVRL3-CASKchr3110845182chrX414692781219HLA-C12:02YISGAVSQV0.97290.93491019
PVRL3-CASKchr3110845182chrX414692781219HLA-C16:01ISGAVSQVL0.91110.96761120
PVRL3-CASKchr3110845182chrX414692781219HLA-B35:13ISGAVSQVL0.82220.82081120
PVRL3-CASKchr3110845182chrX414692781219HLA-C02:10YISGAVSQV0.6990.95561019
PVRL3-CASKchr3110845182chrX414692781219HLA-C02:02YISGAVSQV0.6990.95561019
PVRL3-CASKchr3110845182chrX414692781219HLA-C17:01YISGAVSQV0.64850.96411019
PVRL3-CASKchr3110845182chrX414692781219HLA-B07:13YISGAVSQV0.41360.83971019
PVRL3-CASKchr3110845182chrX414692781219HLA-C07:04YISGAVSQV0.21610.95961019
PVRL3-CASKchr3110845182chrX414692781219HLA-B07:13ISGAVSQVL0.1150.8061120
PVRL3-CASKchr3110845182chrX414692781219HLA-C14:03IYISGAVSQVL0.9790.9416920
PVRL3-CASKchr3110845182chrX414692781219HLA-C14:02IYISGAVSQVL0.9790.9416920

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Potential FusionNeoAntigen Information of PVRL3-CASK 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.
PVRL3-CASK_110845182_41469278.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)
PVRL3-CASKchr3110845182chrX414692781219DRB1-1002SDQKVIYISGAVSQV419

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Fusion breakpoint peptide structures of PVRL3-CASK

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
7368QKVIYISGAVSQVLPVRL3CASKchr3110845182chrX414692781219

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PVRL3-CASK

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-B14:023BVN7368QKVIYISGAVSQVL-7.15543-7.26883
HLA-B14:023BVN7368QKVIYISGAVSQVL-4.77435-5.80965
HLA-B52:013W397368QKVIYISGAVSQVL-6.80875-6.92215
HLA-B52:013W397368QKVIYISGAVSQVL-4.20386-5.23916
HLA-A11:014UQ27368QKVIYISGAVSQVL-7.5194-8.5547
HLA-A11:014UQ27368QKVIYISGAVSQVL-6.9601-7.0735
HLA-A24:025HGA7368QKVIYISGAVSQVL-7.52403-7.63743
HLA-A24:025HGA7368QKVIYISGAVSQVL-5.82433-6.85963
HLA-B27:056PYJ7368QKVIYISGAVSQVL-3.28285-4.31815
HLA-B44:053DX87368QKVIYISGAVSQVL-5.91172-6.94702
HLA-B44:053DX87368QKVIYISGAVSQVL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PVRL3-CASK

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
PVRL3-CASKchr3110845182chrX414692781019YISGAVSQVACATTTCAGGAGCAGTCTCACAGGTGC
PVRL3-CASKchr3110845182chrX414692781120ISGAVSQVLTTTCAGGAGCAGTCTCACAGGTGCTGG
PVRL3-CASKchr3110845182chrX41469278920IYISGAVSQVLTCTACATTTCAGGAGCAGTCTCACAGGTGCTGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PVRL3-CASKchr3110845182chrX41469278419SDQKVIYISGAVSQVGTGACCAAAAAGTCATCTACATTTCAGGAGCAGTCTCACAGGTGC

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Information of the samples that have these potential fusion neoantigens of PVRL3-CASK

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
LGGPVRL3-CASKchr3110845182ENST00000319792chrX41469278ENST00000318588TCGA-HT-7686

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Potential target of CAR-T therapy development for PVRL3-CASK

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 PVRL3-CASK

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 PVRL3-CASK

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