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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:ANKRD52-DYRK2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ANKRD52-DYRK2
FusionPDB ID: 4765
FusionGDB2.0 ID: 4765
HgeneTgene
Gene symbol

ANKRD52

DYRK2

Gene ID

283373

8445

Gene nameankyrin repeat domain 52dual specificity tyrosine phosphorylation regulated kinase 2
SynonymsANKRD33-
Cytomap

12q13.3

12q15

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit CCVWG5837PP6-ARS-Cankyrin repeat domain 33ankyrin repeat domain-containing protein 52protein phosphatase 6 ankyrin repeat subunit Cserine/threonine-protein phosphatase 6 reguladual specificity tyrosine-phosphorylation-regulated kinase 2dual specificity tyrosine-(Y)-phosphorylation regulated kinase 2
Modification date2020031320200313
UniProtAcc

Q8NB46

Main function of 5'-partner protein: FUNCTION: Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates.

Q92630

Main function of 5'-partner protein: FUNCTION: Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). {ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:9748265}.
Ensembl transtripts involved in fusion geneENST idsENST00000267116, ENST00000548241, 
ENST00000393555, ENST00000537632, 
ENST00000344096, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 13 X 5=7808 X 5 X 7=280
# samples 118
** MAII scorelog2(11/780*10)=-2.82597060022495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/280*10)=-1.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ANKRD52 [Title/Abstract] AND DYRK2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ANKRD52 [Title/Abstract] AND DYRK2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ANKRD52(56641277)-DYRK2(68050886), # samples:2
Anticipated loss of major functional domain due to fusion event.ANKRD52-DYRK2 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.
ANKRD52-DYRK2 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
TgeneDYRK2

GO:0006468

protein phosphorylation

11311121

TgeneDYRK2

GO:0042771

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

17349958

TgeneDYRK2

GO:0045725

positive regulation of glycogen biosynthetic process

11311121



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/chr12:56641277/chr12:68050886)
- 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 ANKRD52 (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 DYRK2 (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)
ENST00000267116ANKRD52chr1256641277-ENST00000344096DYRK2chr1268050886+1060723064439131289

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
ENST00000267116ENST00000344096ANKRD52chr1256641277-DYRK2chr1268050886+0.000158690.99984133

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 ANKRD52-DYRK2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ANKRD52chr1256641277DYRK2chr12680508862306754AADLRGRTALHRGIGGSKHTMNDHLH

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Potential FusionNeoAntigen Information of ANKRD52-DYRK2 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.
ANKRD52-DYRK2_56641277_68050886.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)
ANKRD52-DYRK2chr1256641277chr12680508862306HLA-B27:04GRTALHRGI0.9990.5851514
ANKRD52-DYRK2chr1256641277chr12680508862306HLA-A03:25ALHRGIGGSK0.98150.5903818
ANKRD52-DYRK2chr1256641277chr12680508862306HLA-A03:01ALHRGIGGSK0.98150.5903818
ANKRD52-DYRK2chr1256641277chr12680508862306HLA-B27:06GRTALHRGI0.99880.6102514
ANKRD52-DYRK2chr1256641277chr12680508862306HLA-B27:09GRTALHRGI0.9980.5457514

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Potential FusionNeoAntigen Information of ANKRD52-DYRK2 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.
ANKRD52-DYRK2_56641277_68050886.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)
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1102AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1116AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1121AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1155AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1165AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1170AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1301AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1315AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1317AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1319AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1322AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1335AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1351AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1352AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1353AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1357AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1359AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1361AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1364AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1368AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1369AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1379AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1380AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1383AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1387AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1391AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1392AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB1-1398AADLRGRTALHRGIG015
ANKRD52-DYRK2chr1256641277chr12680508862306DRB5-0103AADLRGRTALHRGIG015

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Fusion breakpoint peptide structures of ANKRD52-DYRK2

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
8263RTALHRGIGGSKHTANKRD52DYRK2chr1256641277chr12680508862306

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ANKRD52-DYRK2

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-B14:023BVN8263RTALHRGIGGSKHT-3.07948-3.07948
HLA-A24:025HGA8263RTALHRGIGGSKHT-4.26901-4.26901

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Vaccine Design for the FusionNeoAntigens of ANKRD52-DYRK2

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
ANKRD52-DYRK2chr1256641277chr1268050886514GRTALHRGIGGCCGCACTGCCCTCCACCGCGGGATT
ANKRD52-DYRK2chr1256641277chr1268050886818ALHRGIGGSKGCCCTCCACCGCGGGATTGGCGGCAGTAAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ANKRD52-DYRK2chr1256641277chr1268050886015AADLRGRTALHRGIGGCTGCTGACCTCCGGGGCCGCACTGCCCTCCACCGCGGGATTGGC

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Information of the samples that have these potential fusion neoantigens of ANKRD52-DYRK2

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
ACCANKRD52-DYRK2chr1256641277ENST00000267116chr1268050886ENST00000344096TCGA-OR-A5K9-01A

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Potential target of CAR-T therapy development for ANKRD52-DYRK2

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 ANKRD52-DYRK2

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 ANKRD52-DYRK2

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