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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:CDK19-CPM

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CDK19-CPM
FusionPDB ID: 15215
FusionGDB2.0 ID: 15215
HgeneTgene
Gene symbol

CDK19

CPM

Gene ID

23097

1368

Gene namecyclin dependent kinase 19carboxypeptidase M
SynonymsCDC2L6|CDK11|bA346C16.3-
Cytomap

6q21

12q15

Type of geneprotein-codingprotein-coding
Descriptioncyclin-dependent kinase 19CDC2-related protein kinase 6CDK8-like cyclin-dependent kinasecell division cycle 2-like 6 (CDK8-like)cell division cycle 2-like protein kinase 6cell division protein kinase 19cyclin dependent kinase 19 variant 2cyclin-depcarboxypeptidase Mrenal carboxypeptidaseurinary carboxypeptidase B
Modification date2020031320200313
UniProtAcc

Q9BWU1

Main function of 5'-partner protein:

P14384

Main function of 5'-partner protein: FUNCTION: Specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins. It is believed to play important roles in the control of peptide hormone and growth factor activity at the cell surface, and in the membrane-localized degradation of extracellular proteins. {ECO:0000269|PubMed:12457462}.
Ensembl transtripts involved in fusion geneENST idsENST00000323817, ENST00000368911, 
ENST00000413605, ENST00000497709, 
ENST00000549691, ENST00000338356, 
ENST00000546373, ENST00000551568, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 10 X 7=84048 X 16 X 10=7680
# samples 1545
** MAII scorelog2(15/840*10)=-2.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(45/7680*10)=-4.09310940439148
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CDK19 [Title/Abstract] AND CPM [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CDK19 [Title/Abstract] AND CPM [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CDK19(111067329)-CPM(69265736), # samples:1
Anticipated loss of major functional domain due to fusion event.CDK19-CPM 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.
CDK19-CPM 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.
CDK19-CPM seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
CDK19-CPM seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CDK19-CPM seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
CDK19-CPM seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
CDK19-CPM seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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


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/chr6:111067329/chr12:69265736)
- 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 CDK19 (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 CPM (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)
ENST00000368911CDK19chr6111067329-ENST00000546373CPMchr1269265736-21383841801457425
ENST00000368911CDK19chr6111067329-ENST00000551568CPMchr1269265736-67203841801457425
ENST00000368911CDK19chr6111067329-ENST00000338356CPMchr1269265736-67153841801457425

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
ENST00000368911ENST00000546373CDK19chr6111067329-CPMchr1269265736-0.0004363910.99956363
ENST00000368911ENST00000551568CDK19chr6111067329-CPMchr1269265736-0.000350440.9996495
ENST00000368911ENST00000338356CDK19chr6111067329-CPMchr1269265736-0.0003527440.99964726

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 CDK19-CPM

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CDK19chr6111067329CPMchr126926573638466IEGTGISMSACREIATVGRELLLHLI

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Potential FusionNeoAntigen Information of CDK19-CPM 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.
CDK19-CPM_111067329_69265736.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)
CDK19-CPMchr6111067329chr1269265736384HLA-A26:14EIATVGREL0.99530.54211221
CDK19-CPMchr6111067329chr1269265736384HLA-A26:15EIATVGREL0.99530.54211221
CDK19-CPMchr6111067329chr1269265736384HLA-A66:01EIATVGREL0.99370.53821221
CDK19-CPMchr6111067329chr1269265736384HLA-A26:03EIATVGREL0.99280.54441221
CDK19-CPMchr6111067329chr1269265736384HLA-B47:01REIATVGREL0.98780.5341121
CDK19-CPMchr6111067329chr1269265736384HLA-B44:03REIATVGREL0.90120.93511121
CDK19-CPMchr6111067329chr1269265736384HLA-B39:13REIATVGREL0.85290.93561121
CDK19-CPMchr6111067329chr1269265736384HLA-A26:01EIATVGREL0.99530.54211221
CDK19-CPMchr6111067329chr1269265736384HLA-B40:06REIATVGREL0.99860.66891121
CDK19-CPMchr6111067329chr1269265736384HLA-B39:08REIATVGREL0.95810.89481121
CDK19-CPMchr6111067329chr1269265736384HLA-A25:01EIATVGREL0.99770.90381221
CDK19-CPMchr6111067329chr1269265736384HLA-A68:02EIATVGREL0.97580.50021221
CDK19-CPMchr6111067329chr1269265736384HLA-A69:01EIATVGREL0.86530.62331221
CDK19-CPMchr6111067329chr1269265736384HLA-B40:04REIATVGREL0.99650.67461121
CDK19-CPMchr6111067329chr1269265736384HLA-B44:26REIATVGREL0.90120.93511121
CDK19-CPMchr6111067329chr1269265736384HLA-B44:13REIATVGREL0.90120.93511121
CDK19-CPMchr6111067329chr1269265736384HLA-B44:07REIATVGREL0.90120.93511121
CDK19-CPMchr6111067329chr1269265736384HLA-B39:02REIATVGREL0.89720.93421121
CDK19-CPMchr6111067329chr1269265736384HLA-B41:03REIATVGREL0.80070.71991121
CDK19-CPMchr6111067329chr1269265736384HLA-B40:04REIATVGRELL0.99960.61051122

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Potential FusionNeoAntigen Information of CDK19-CPM 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 CDK19-CPM

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
8832SMSACREIATVGRECDK19CPMchr6111067329chr1269265736384

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CDK19-CPM

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-B14:023BVN8832SMSACREIATVGRE-7.37157-7.48337
HLA-B14:023BVN8832SMSACREIATVGRE-5.75216-6.79526
HLA-B52:013W398832SMSACREIATVGRE-7.36854-7.48034
HLA-B52:013W398832SMSACREIATVGRE-4.42371-5.46681
HLA-A11:014UQ28832SMSACREIATVGRE-8.60667-9.64977
HLA-A11:014UQ28832SMSACREIATVGRE-5.54504-5.65684
HLA-A24:025HGA8832SMSACREIATVGRE-7.65859-7.77039
HLA-A24:025HGA8832SMSACREIATVGRE-6.03094-7.07404
HLA-B44:053DX88832SMSACREIATVGRE-5.82315-5.93495
HLA-B44:053DX88832SMSACREIATVGRE-2.98805-4.03115

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Vaccine Design for the FusionNeoAntigens of CDK19-CPM

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
CDK19-CPMchr6111067329chr12692657361121REIATVGRELATTGCAACTGTTGGGCGGGAGCTGCTGCTC
CDK19-CPMchr6111067329chr12692657361122REIATVGRELLATTGCAACTGTTGGGCGGGAGCTGCTGCTCCAT
CDK19-CPMchr6111067329chr12692657361221EIATVGRELGCAACTGTTGGGCGGGAGCTGCTGCTC

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 CDK19-CPM

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
SARCCDK19-CPMchr6111067329ENST00000368911chr1269265736ENST00000338356TCGA-DX-A1L4-01A

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Potential target of CAR-T therapy development for CDK19-CPM

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 CDK19-CPM

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 CDK19-CPM

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