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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:DGKE-KRT222

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DGKE-KRT222
FusionPDB ID: 22467
FusionGDB2.0 ID: 22467
HgeneTgene
Gene symbol

DGKE

KRT222

Gene ID

8526

125113

Gene namediacylglycerol kinase epsilonkeratin 222
SynonymsAHUS7|DAGK5|DAGK6|DGK|NPHS7KA21|KRT222P
Cytomap

17q22

17q21.2

Type of geneprotein-codingprotein-coding
Descriptiondiacylglycerol kinase epsilonDAG kinase epsilonDGK-epsilondiacylglycerol kinase, epsilon 64kDadiglyceride kinase epsilonkeratin-like protein KRT222keratin 222, type IIkeratin-222 pseudogene
Modification date2020031320200313
UniProtAcc

P52429

Main function of 5'-partner protein: FUNCTION: Membrane-bound diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:15544348, PubMed:19744926, PubMed:22108654, PubMed:21477596, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:8626589, PubMed:15544348). Also plays an important role in the biosynthesis of complex lipids (PubMed:8626589). Displays specificity for diacylglycerol substrates with an arachidonoyl acyl chain at the sn-2 position, with the highest activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol the main diacylglycerol intermediate within the phosphatidylinositol turnover cycle (PubMed:19744926, PubMed:22108654, PubMed:23274426). Can also phosphorylate diacylglycerol substrates with a linoleoyl acyl chain at the sn-2 position but much less efficiently (PubMed:22108654). {ECO:0000269|PubMed:15544348, ECO:0000269|PubMed:19744926, ECO:0000269|PubMed:21477596, ECO:0000269|PubMed:22108654, ECO:0000269|PubMed:23274426, ECO:0000269|PubMed:23949095, ECO:0000303|PubMed:15544348, ECO:0000303|PubMed:8626589}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000576869, ENST00000284061, 
ENST00000572810, 
ENST00000394052, 
ENST00000476049, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 1 X 2=47 X 5 X 5=175
# samples 210
** MAII scorelog2(2/4*10)=2.32192809488736log2(10/175*10)=-0.807354922057604
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DGKE [Title/Abstract] AND KRT222 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DGKE [Title/Abstract] AND KRT222 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DGKE(54912620)-KRT222(38814002), # samples:2
Anticipated loss of major functional domain due to fusion event.DGKE-KRT222 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.
DGKE-KRT222 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.
DGKE-KRT222 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.
DGKE-KRT222 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.
DGKE-KRT222 seems lost the major protein functional domain in Hgene 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
HgeneDGKE

GO:0046834

lipid phosphorylation

18004883



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/chr17:54912620/chr17:38814002)
- 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 DGKE (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 KRT222 (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)
ENST00000284061DGKEchr1754912620+ENST00000394052KRT222chr1738814002-12586441711085304
ENST00000572810DGKEchr1754912620+ENST00000476049KRT222chr1738814002-3375136123553374340

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
ENST00000284061ENST00000394052DGKEchr1754912620+KRT222chr1738814002-0.0109709490.98902905
ENST00000572810ENST00000476049DGKEchr1754912620+KRT222chr1738814002-0.009429080.9905709

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 DGKE-KRT222

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DGKEchr1754912620KRT222chr1738814002644153CMVCKQQCGCQPKLCDYRYYGCIQGG

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Potential FusionNeoAntigen Information of DGKE-KRT222 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.
DGKE-KRT222_54912620_38814002.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)
DGKE-KRT222chr1754912620chr1738814002644HLA-B35:01QPKLCDYRY0.92560.86341019
DGKE-KRT222chr1754912620chr1738814002644HLA-B35:08QPKLCDYRY0.89840.82761019
DGKE-KRT222chr1754912620chr1738814002644HLA-B48:01QQCGCQPKL0.86360.562514
DGKE-KRT222chr1754912620chr1738814002644HLA-B13:02QQCGCQPKL0.29750.6078514
DGKE-KRT222chr1754912620chr1738814002644HLA-B13:01QQCGCQPKL0.20570.9566514
DGKE-KRT222chr1754912620chr1738814002644HLA-B35:77QPKLCDYRY0.92560.86341019
DGKE-KRT222chr1754912620chr1738814002644HLA-B35:23QPKLCDYRY0.92540.84591019
DGKE-KRT222chr1754912620chr1738814002644HLA-B35:17QPKLCDYRY0.89530.71181019
DGKE-KRT222chr1754912620chr1738814002644HLA-B35:30QPKLCDYRY0.89530.71181019
DGKE-KRT222chr1754912620chr1738814002644HLA-B35:24QPKLCDYRY0.88130.83851019
DGKE-KRT222chr1754912620chr1738814002644HLA-B15:11QPKLCDYRY0.21060.5951019
DGKE-KRT222chr1754912620chr1738814002644HLA-B18:07QPKLCDYRY0.17690.68931019
DGKE-KRT222chr1754912620chr1738814002644HLA-B35:43QPKLCDYRY0.17320.58751019

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Potential FusionNeoAntigen Information of DGKE-KRT222 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 DGKE-KRT222

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
7164QCGCQPKLCDYRYYDGKEKRT222chr1754912620chr1738814002644

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DGKE-KRT222

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-B14:023BVN7164QCGCQPKLCDYRYY-7.15543-7.26883
HLA-B14:023BVN7164QCGCQPKLCDYRYY-4.77435-5.80965
HLA-B52:013W397164QCGCQPKLCDYRYY-6.80875-6.92215
HLA-B52:013W397164QCGCQPKLCDYRYY-4.20386-5.23916
HLA-A11:014UQ27164QCGCQPKLCDYRYY-7.5194-8.5547
HLA-A11:014UQ27164QCGCQPKLCDYRYY-6.9601-7.0735
HLA-A24:025HGA7164QCGCQPKLCDYRYY-7.52403-7.63743
HLA-A24:025HGA7164QCGCQPKLCDYRYY-5.82433-6.85963
HLA-B27:056PYJ7164QCGCQPKLCDYRYY-3.28285-4.31815
HLA-B44:053DX87164QCGCQPKLCDYRYY-5.91172-6.94702
HLA-B44:053DX87164QCGCQPKLCDYRYY-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of DGKE-KRT222

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
DGKE-KRT222chr1754912620chr17388140021019QPKLCDYRYCGATTACAGATATTATGGTTGTATCCA
DGKE-KRT222chr1754912620chr1738814002514QQCGCQPKLTCAACCCAAGCTTTGCGATTACAGATA

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 DGKE-KRT222

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
BRCADGKE-KRT222chr1754912620ENST00000284061chr1738814002ENST00000394052TCGA-C8-A275-01A

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Potential target of CAR-T therapy development for DGKE-KRT222

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
HgeneDGKEchr17:54912620chr17:38814002ENST00000284061+21222_42154568.0TransmembraneHelical

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 DGKE-KRT222

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 DGKE-KRT222

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