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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:ZNF738-DAPK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZNF738-DAPK1
FusionPDB ID: 102858
FusionGDB2.0 ID: 102858
HgeneTgene
Gene symbol

ZNF738

DAPK1

Gene ID

148203

1612

Gene namezinc finger protein 738death associated protein kinase 1
Synonyms-DAPK|ROCO3
Cytomap

19p12

9q21.33

Type of geneprotein-codingprotein-coding
Descriptionprotein ZNF738death-associated protein kinase 1DAP kinase 1
Modification date2020031320200313
UniProtAcc.

P53355

Main function of 5'-partner protein: FUNCTION: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.; FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane blebbing.
Ensembl transtripts involved in fusion geneENST idsENST00000311015, ENST00000380870, 
ENST00000597810, ENST00000594245, 
ENST00000466188, ENST00000491893, 
ENST00000358077, ENST00000408954, 
ENST00000469640, ENST00000472284, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 5 X 5=1759 X 8 X 6=432
# samples 79
** MAII scorelog2(7/175*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/432*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZNF738 [Title/Abstract] AND DAPK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZNF738 [Title/Abstract] AND DAPK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZNF738(21558766)-DAPK1(90311922), # samples:1
Anticipated loss of major functional domain due to fusion event.ZNF738-DAPK1 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.
ZNF738-DAPK1 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.
ZNF738-DAPK1 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.
ZNF738-DAPK1 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
TgeneDAPK1

GO:0006468

protein phosphorylation

10629061

TgeneDAPK1

GO:0017148

negative regulation of translation

18995835

TgeneDAPK1

GO:0035556

intracellular signal transduction

10629061

TgeneDAPK1

GO:0043280

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

16132846

TgeneDAPK1

GO:0046777

protein autophosphorylation

10629061|12730201

TgeneDAPK1

GO:0071346

cellular response to interferon-gamma

18995835



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/chr19:21558766/chr9:90311922)
- 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 ZNF738 (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 DAPK1 (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)
ENST00000311015ZNF738chr1921558766+ENST00000358077DAPK1chr990311922+3677530192409796
ENST00000311015ZNF738chr1921558766+ENST00000472284DAPK1chr990311922+3676530192409796
ENST00000311015ZNF738chr1921558766+ENST00000469640DAPK1chr990311922+3754530192484821
ENST00000311015ZNF738chr1921558766+ENST00000408954DAPK1chr990311922+3674530192409796
ENST00000380870ZNF738chr1921558766+ENST00000358077DAPK1chr990311922+36154681492347732
ENST00000380870ZNF738chr1921558766+ENST00000472284DAPK1chr990311922+36144681492347732
ENST00000380870ZNF738chr1921558766+ENST00000469640DAPK1chr990311922+36924681492422757
ENST00000380870ZNF738chr1921558766+ENST00000408954DAPK1chr990311922+36124681492347732
ENST00000597810ZNF738chr1921558766+ENST00000358077DAPK1chr990311922+35964491302328732
ENST00000597810ZNF738chr1921558766+ENST00000472284DAPK1chr990311922+35954491302328732
ENST00000597810ZNF738chr1921558766+ENST00000469640DAPK1chr990311922+36734491302403757
ENST00000597810ZNF738chr1921558766+ENST00000408954DAPK1chr990311922+35934491302328732

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
ENST00000311015ENST00000358077ZNF738chr1921558766+DAPK1chr990311922+0.0015321630.99846786
ENST00000311015ENST00000472284ZNF738chr1921558766+DAPK1chr990311922+0.0015208420.9984792
ENST00000311015ENST00000469640ZNF738chr1921558766+DAPK1chr990311922+0.0013791850.99862087
ENST00000311015ENST00000408954ZNF738chr1921558766+DAPK1chr990311922+0.0014945910.9985055
ENST00000380870ENST00000358077ZNF738chr1921558766+DAPK1chr990311922+0.0014784470.9985216
ENST00000380870ENST00000472284ZNF738chr1921558766+DAPK1chr990311922+0.0014675830.9985324
ENST00000380870ENST00000469640ZNF738chr1921558766+DAPK1chr990311922+0.0013321620.99866784
ENST00000380870ENST00000408954ZNF738chr1921558766+DAPK1chr990311922+0.0014414030.9985586
ENST00000597810ENST00000358077ZNF738chr1921558766+DAPK1chr990311922+0.0014717620.99852824
ENST00000597810ENST00000472284ZNF738chr1921558766+DAPK1chr990311922+0.0014604870.99853957
ENST00000597810ENST00000469640ZNF738chr1921558766+DAPK1chr990311922+0.0013275450.9986725
ENST00000597810ENST00000408954ZNF738chr1921558766+DAPK1chr990311922+0.0014283230.99857163

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 ZNF738-DAPK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZNF738chr1921558766DAPK1chr990311922449106WNMKRHSMVATPPGVGDFSVWEFSGN
ZNF738chr1921558766DAPK1chr990311922468106WNMKRHSMVATPPGVGDFSVWEFSGN
ZNF738chr1921558766DAPK1chr990311922530170WNMKRHSMVATPPGVGDFSVWEFSGN

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Potential FusionNeoAntigen Information of ZNF738-DAPK1 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.
ZNF738-DAPK1_21558766_90311922.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)
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:22SMVATPPGV0.99250.6184615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:21SMVATPPGV0.98780.753615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:13SMVATPPGV0.98770.7863615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:67SMVATPPGV0.98760.6434615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:30SMVATPPGV0.98760.6434615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:11SMVATPPGV0.98760.6783615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:60SMVATPPGV0.98760.6111615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:24SMVATPPGV0.98760.6434615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:27SMVATPPGV0.98750.697615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:38SMVATPPGV0.98370.6896615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:35SMVATPPGV0.98060.6579615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:29SMVATPPGV0.97340.6428615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:04SMVATPPGV0.97030.8335615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:20SMVATPPGV0.96890.6525615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:19SMVATPPGV0.95920.5595615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:17SMVATPPGV0.94360.7269615
ZNF738-DAPK1chr1921558766chr990311922530HLA-B13:02SMVATPPGV0.04580.9294615
ZNF738-DAPK1chr1921558766chr990311922530HLA-B53:01PPGVGDFSVW0.80350.69051121
ZNF738-DAPK1chr1921558766chr990311922530HLA-B53:01TPPGVGDFSVW0.98710.64981021
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:01SMVATPPGV0.98760.6434615
ZNF738-DAPK1chr1921558766chr990311922530HLA-C01:17ATPPGVGDF0.05930.9189918
ZNF738-DAPK1chr1921558766chr990311922530HLA-C01:30ATPPGVGDF0.01940.9052918
ZNF738-DAPK1chr1921558766chr990311922530HLA-C03:07VATPPGVGDF0.9970.9564818
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:03SMVATPPGV0.99380.819615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:14SMVATPPGV0.98780.6911615
ZNF738-DAPK1chr1921558766chr990311922530HLA-A02:06SMVATPPGV0.98780.753615
ZNF738-DAPK1chr1921558766chr990311922530HLA-C01:02ATPPGVGDF0.06580.9121918
ZNF738-DAPK1chr1921558766chr990311922530HLA-C01:03ATPPGVGDF0.02420.849918
ZNF738-DAPK1chr1921558766chr990311922530HLA-C03:02VATPPGVGDF0.99890.9486818
ZNF738-DAPK1chr1921558766chr990311922530HLA-B53:02TPPGVGDFSVW0.98620.59711021

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Potential FusionNeoAntigen Information of ZNF738-DAPK1 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 ZNF738-DAPK1

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
8835SMVATPPGVGDFSVZNF738DAPK1chr1921558766chr990311922530

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZNF738-DAPK1

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-B14:023BVN8835SMVATPPGVGDFSV-5.47913-5.67113
HLA-B14:023BVN8835SMVATPPGVGDFSV-3.84443-4.60543
HLA-B52:013W398835SMVATPPGVGDFSV-6.76995-6.96195
HLA-B52:013W398835SMVATPPGVGDFSV-5.58751-6.34851
HLA-A11:014UQ28835SMVATPPGVGDFSV-5.74663-6.50763
HLA-A11:014UQ28835SMVATPPGVGDFSV-5.69582-5.88782
HLA-A24:025HGA8835SMVATPPGVGDFSV-8.42283-9.18383
HLA-A24:025HGA8835SMVATPPGVGDFSV-7.2103-7.4023
HLA-B27:056PYJ8835SMVATPPGVGDFSV-7.69112-7.88312
HLA-B44:053DX88835SMVATPPGVGDFSV-5.89348-6.08548
HLA-B44:053DX88835SMVATPPGVGDFSV-3.81554-4.57654
HLA-A02:016TDR8835SMVATPPGVGDFSV-3.68024-4.44124

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Vaccine Design for the FusionNeoAntigens of ZNF738-DAPK1

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
ZNF738-DAPK1chr1921558766chr9903119221021TPPGVGDFSVWCACCCCCAGGAGTTGGCGATTTCAGCGTGTGGG
ZNF738-DAPK1chr1921558766chr9903119221121PPGVGDFSVWCCCCAGGAGTTGGCGATTTCAGCGTGTGGG
ZNF738-DAPK1chr1921558766chr990311922615SMVATPPGVGTATGGTAGCCACACCCCCAGGAGTTG
ZNF738-DAPK1chr1921558766chr990311922818VATPPGVGDFTAGCCACACCCCCAGGAGTTGGCGATTTCA
ZNF738-DAPK1chr1921558766chr990311922918ATPPGVGDFCCACACCCCCAGGAGTTGGCGATTTCA

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 ZNF738-DAPK1

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
BRCAZNF738-DAPK1chr1921558766ENST00000311015chr990311922ENST00000358077TCGA-E2-A1LG-01A

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Potential target of CAR-T therapy development for ZNF738-DAPK1

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 ZNF738-DAPK1

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 ZNF738-DAPK1

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