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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:PRKD2-GLUD1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRKD2-GLUD1
FusionPDB ID: 68813
FusionGDB2.0 ID: 68813
HgeneTgene
Gene symbol

PRKD2

GLUD1

Gene ID

25865

2746

Gene nameprotein kinase D2glutamate dehydrogenase 1
SynonymsHSPC187|PKD2|nPKC-D2GDH|GDH1|GLUD
Cytomap

19q13.32

10q23.2

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase D2glutamate dehydrogenase 1, mitochondrialepididymis secretory sperm binding proteinepididymis tissue sperm binding protein Li 18mPglutamate dehydrogenase (NAD(P)+)
Modification date2020032920200329
UniProtAcc.

P00367

Main function of 5'-partner protein: FUNCTION: Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (PubMed:11032875, PubMed:16959573, PubMed:11254391, PubMed:16023112). Plays a role in insulin homeostasis (PubMed:9571255, PubMed:11297618). May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity). {ECO:0000250|UniProtKB:P10860, ECO:0000269|PubMed:11032875, ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11297618, ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573, ECO:0000269|PubMed:9571255}.
Ensembl transtripts involved in fusion geneENST idsENST00000291281, ENST00000433867, 
ENST00000595515, ENST00000600194, 
ENST00000601806, ENST00000593492, 
ENST00000465164, ENST00000277865, 
ENST00000537649, ENST00000544149, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 8 X 9=64810 X 7 X 8=560
# samples 1111
** MAII scorelog2(11/648*10)=-2.55849028935997
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/560*10)=-2.34792330342031
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PRKD2 [Title/Abstract] AND GLUD1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PRKD2 [Title/Abstract] AND GLUD1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRKD2(47192794)-GLUD1(88819030), # samples:1
Anticipated loss of major functional domain due to fusion event.PRKD2-GLUD1 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.
PRKD2-GLUD1 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.
PRKD2-GLUD1 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.
PRKD2-GLUD1 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.
PRKD2-GLUD1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PRKD2-GLUD1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PRKD2-GLUD1 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
PRKD2-GLUD1 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene 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
HgenePRKD2

GO:0006468

protein phosphorylation

22228765

HgenePRKD2

GO:0018105

peptidyl-serine phosphorylation

18440775

HgenePRKD2

GO:0045944

positive regulation of transcription by RNA polymerase II

17077180

HgenePRKD2

GO:0046777

protein autophosphorylation

17077180

HgenePRKD2

GO:0050852

T cell receptor signaling pathway

17077180

TgeneGLUD1

GO:0006537

glutamate biosynthetic process

11032875

TgeneGLUD1

GO:0006538

glutamate catabolic process

6121377|11032875



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/chr19:47192794/chr10:88819030)
- 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 PRKD2 (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 GLUD1 (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)
ENST00000291281PRKD2chr1947192794-ENST00000277865GLUD1chr1088819030-386121971272595822
ENST00000291281PRKD2chr1947192794-ENST00000537649GLUD1chr1088819030-385721971272595822
ENST00000291281PRKD2chr1947192794-ENST00000544149GLUD1chr1088819030-274621971272595822
ENST00000433867PRKD2chr1947192794-ENST00000277865GLUD1chr1088819030-411324492172847876
ENST00000433867PRKD2chr1947192794-ENST00000537649GLUD1chr1088819030-410924492172847876
ENST00000433867PRKD2chr1947192794-ENST00000544149GLUD1chr1088819030-299824492172847876

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
ENST00000291281ENST00000277865PRKD2chr1947192794-GLUD1chr1088819030-0.001623890.99837613
ENST00000291281ENST00000537649PRKD2chr1947192794-GLUD1chr1088819030-0.0016324360.9983676
ENST00000291281ENST00000544149PRKD2chr1947192794-GLUD1chr1088819030-0.0051425750.99485743
ENST00000433867ENST00000277865PRKD2chr1947192794-GLUD1chr1088819030-0.0017872390.9982128
ENST00000433867ENST00000537649PRKD2chr1947192794-GLUD1chr1088819030-0.0017906480.99820936
ENST00000433867ENST00000544149PRKD2chr1947192794-GLUD1chr1088819030-0.005626390.99437356

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 PRKD2-GLUD1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PRKD2chr1947192794GLUD1chr10888190302197690RLPERLTKFLITQDLYLNAGGVTVSY
PRKD2chr1947192794GLUD1chr10888190302449744RLPERLTKFLITQDLYLNAGGVTVSY

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Potential FusionNeoAntigen Information of PRKD2-GLUD1 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.
PRKD2-GLUD1_47192794_88819030.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)
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B39:24TKFLITQDL0.99310.5449615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B14:02TKFLITQDL0.98830.7951615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B14:01TKFLITQDL0.98830.7951615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B39:01TKFLITQDL0.98580.9524615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-A02:13FLITQDLYL0.97550.6074817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-A02:38FLITQDLYL0.95240.6846817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B15:10TKFLITQDL0.67770.5321615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B15:37TKFLITQDL0.33920.5691615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-A02:05FLITQDLYL0.99270.5167817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B39:09TKFLITQDL0.98950.7509615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C03:07FLITQDLYL0.97770.9277817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B39:05TKFLITQDL0.97390.942615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C05:09FLITQDLYL0.96150.9303817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C04:06FLITQDLYL0.94040.8711817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C03:19FLITQDLYL0.92970.9742817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C08:13FLITQDLYL0.86480.9344817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C08:04FLITQDLYL0.86480.9344817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C04:14FLITQDLYL0.82030.7724817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C08:03FLITQDLYL0.79950.9832817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C02:06FLITQDLYL0.6610.9286817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C07:13FLITQDLYL0.52330.8983817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C07:29FLITQDLYL0.50050.9175817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B39:31TKFLITQDL0.99020.9533615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-A02:03FLITQDLYL0.98840.5482817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C03:03FLITQDLYL0.96390.9763817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C03:04FLITQDLYL0.96390.9763817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C04:03FLITQDLYL0.96360.8576817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C05:01FLITQDLYL0.96150.9303817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C18:01FLITQDLYL0.92550.8299817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C03:06FLITQDLYL0.9180.9792817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C03:67FLITQDLYL0.89910.9629817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C04:04FLITQDLYL0.85610.8562817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C01:03FLITQDLYL0.81990.9047817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C08:01FLITQDLYL0.79950.9832817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C17:01FLITQDLYL0.70880.8072817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B15:09TKFLITQDL0.6240.8271615
PRKD2-GLUD1chr1947192794chr10888190302197HLA-B15:30FLITQDLYL0.58630.8654817
PRKD2-GLUD1chr1947192794chr10888190302197HLA-C07:04FLITQDLYL0.49380.8919817

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Potential FusionNeoAntigen Information of PRKD2-GLUD1 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 PRKD2-GLUD1

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
9431TKFLITQDLYLNAGPRKD2GLUD1chr1947192794chr10888190302197

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PRKD2-GLUD1

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-B14:023BVN9431TKFLITQDLYLNAG-7.9962-8.1096
HLA-B14:023BVN9431TKFLITQDLYLNAG-5.70842-6.74372
HLA-B52:013W399431TKFLITQDLYLNAG-6.83737-6.95077
HLA-B52:013W399431TKFLITQDLYLNAG-4.4836-5.5189
HLA-A11:014UQ29431TKFLITQDLYLNAG-10.0067-10.1201
HLA-A11:014UQ29431TKFLITQDLYLNAG-9.03915-10.0745
HLA-A24:025HGA9431TKFLITQDLYLNAG-6.56204-6.67544
HLA-A24:025HGA9431TKFLITQDLYLNAG-5.42271-6.45801
HLA-B44:053DX89431TKFLITQDLYLNAG-7.85648-8.89178
HLA-B44:053DX89431TKFLITQDLYLNAG-5.3978-5.5112
HLA-A02:016TDR9431TKFLITQDLYLNAG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PRKD2-GLUD1

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
PRKD2-GLUD1chr1947192794chr1088819030615TKFLITQDLACCAAGTTCCTCATCACCCAGGATCTC
PRKD2-GLUD1chr1947192794chr1088819030817FLITQDLYLTTCCTCATCACCCAGGATCTCTACTTG

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 PRKD2-GLUD1

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
PRADPRKD2-GLUD1chr1947192794ENST00000291281chr1088819030ENST00000277865TCGA-J4-A67S-01A

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Potential target of CAR-T therapy development for PRKD2-GLUD1

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 PRKD2-GLUD1

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 PRKD2-GLUD1

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