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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:CPSF6-MYF6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CPSF6-MYF6
FusionPDB ID: 19168
FusionGDB2.0 ID: 19168
HgeneTgene
Gene symbol

CPSF6

MYF6

Gene ID

11052

4618

Gene namecleavage and polyadenylation specific factor 6myogenic factor 6
SynonymsCFIM|CFIM68|CFIM72|HPBRII-4|HPBRII-7CNM3|MRF4|bHLHc4|myf-6
Cytomap

12q15

12q21.31

Type of geneprotein-codingprotein-coding
Descriptioncleavage and polyadenylation specificity factor subunit 6CPSF 68 kDa subunitcleavage and polyadenylation specific factor 6, 68kDacleavage and polyadenylation specificity factor 68 kDa subunitcleavage factor Im complex 68 kDa subunitpre-mRNA cleavage myogenic factor 6class C basic helix-loop-helix protein 4muscle-specific regulatory factor 4myogenic factor 6 (herculin)
Modification date2020031320200313
UniProtAcc

Q16630

Main function of 5'-partner protein: FUNCTION: Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:9659921, PubMed:8626397, PubMed:14690600, PubMed:29276085). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:9659921, PubMed:8626397, PubMed:14690600). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:20695905, PubMed:29276085). CPSF6 enhances NUDT21/CPSF5 binding to 5'-UGUA-3' elements localized upstream of pA signals and promotes RNA looping, and hence activates directly the mRNA 3'-processing machinery (PubMed:15169763, PubMed:29276085, PubMed:21295486). Plays a role in mRNA export (PubMed:19864460). {ECO:0000269|PubMed:14690600, ECO:0000269|PubMed:15169763, ECO:0000269|PubMed:19864460, ECO:0000269|PubMed:20695905, ECO:0000269|PubMed:21295486, ECO:0000269|PubMed:23187700, ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:8626397, ECO:0000269|PubMed:9659921}.; FUNCTION: (Microbial infection) Binds HIV-1 capsid-nucleocapsid (HIV-1 CA-NC) complexes and might thereby promote the integration of the virus in the nucleus of dividing cells (in vitro). {ECO:0000269|PubMed:24130490}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000550987, ENST00000266679, 
ENST00000435070, ENST00000456847, 
ENST00000551516, 
ENST00000228641, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score69 X 12 X 19=157323 X 1 X 2=6
# samples 713
** MAII scorelog2(71/15732*10)=-4.46973925655087
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/6*10)=2.32192809488736
Fusion gene context

PubMed: CPSF6 [Title/Abstract] AND MYF6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CPSF6 [Title/Abstract] AND MYF6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CPSF6(69633486)-MYF6(81101634), # samples:2
Anticipated loss of major functional domain due to fusion event.CPSF6-MYF6 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.
CPSF6-MYF6 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.
CPSF6-MYF6 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.
CPSF6-MYF6 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
HgeneCPSF6

GO:0006397

mRNA processing

14690600

HgeneCPSF6

GO:0051262

protein tetramerization

20695905

HgeneCPSF6

GO:0051290

protein heterotetramerization

23187700

HgeneCPSF6

GO:1990120

messenger ribonucleoprotein complex assembly

29276085



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/chr12:69633486/chr12:81101634)
- 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 CPSF6 (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 MYF6 (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)
ENST00000435070CPSF6chr1269633486+ENST00000228641MYF6chr1281101634+1277170100762220
ENST00000456847CPSF6chr1269633486+ENST00000228641MYF6chr1281101634+121410737699220
ENST00000266679CPSF6chr1269633486+ENST00000228641MYF6chr1281101634+11989121683220
ENST00000551516CPSF6chr1269633486+ENST00000228641MYF6chr1281101634+11726570657195

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
ENST00000435070ENST00000228641CPSF6chr1269633486+MYF6chr1281101634+0.0248569230.9751431
ENST00000456847ENST00000228641CPSF6chr1269633486+MYF6chr1281101634+0.0218234060.97817665
ENST00000266679ENST00000228641CPSF6chr1269633486+MYF6chr1281101634+0.0195574180.9804426
ENST00000551516ENST00000228641CPSF6chr1269633486+MYF6chr1281101634+0.0174539150.9825461

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 CPSF6-MYF6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CPSF6chr1269633486MYF6chr128110163410723HRHLRGCRRRVQPDQMPPEAGSDSSG
CPSF6chr1269633486MYF6chr128110163417023HRHLRGCRRRVQPDQMPPEAGSDSSG
CPSF6chr1269633486MYF6chr12811016349123HRHLRGCRRRVQPDQMPPEAGSDSSG

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Potential FusionNeoAntigen Information of CPSF6-MYF6 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.
CPSF6-MYF6_69633486_81101634.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)
CPSF6-MYF6chr1269633486chr128110163491HLA-B56:01QPDQMPPEA0.86610.91711120
CPSF6-MYF6chr1269633486chr128110163491HLA-B55:01QPDQMPPEA0.83820.74131120
CPSF6-MYF6chr1269633486chr128110163491HLA-B35:03QPDQMPPEA0.63640.9621120
CPSF6-MYF6chr1269633486chr128110163491HLA-B35:08QPDQMPPEA0.62380.95651120
CPSF6-MYF6chr1269633486chr128110163491HLA-B35:02QPDQMPPEA0.48120.98781120
CPSF6-MYF6chr1269633486chr128110163491HLA-B35:04QPDQMPPEA0.48120.98781120
CPSF6-MYF6chr1269633486chr128110163491HLA-B82:01QPDQMPPEA0.3770.88191120
CPSF6-MYF6chr1269633486chr128110163491HLA-B07:10RRRVQPDQM0.05390.5901716
CPSF6-MYF6chr1269633486chr128110163491HLA-C07:05RRRVQPDQM0.98730.8847716
CPSF6-MYF6chr1269633486chr128110163491HLA-B54:01QPDQMPPEA0.92250.93691120
CPSF6-MYF6chr1269633486chr128110163491HLA-C07:46RRRVQPDQM0.83580.7755716
CPSF6-MYF6chr1269633486chr128110163491HLA-B73:01RRVQPDQMP0.82160.8838817
CPSF6-MYF6chr1269633486chr128110163491HLA-B56:04QPDQMPPEA0.59860.9691120
CPSF6-MYF6chr1269633486chr128110163491HLA-B78:01QPDQMPPEA0.49570.9921120
CPSF6-MYF6chr1269633486chr128110163491HLA-B35:12QPDQMPPEA0.48120.98781120
CPSF6-MYF6chr1269633486chr128110163491HLA-B39:10QPDQMPPEA0.28790.99311120
CPSF6-MYF6chr1269633486chr128110163491HLA-C07:22RRRVQPDQM0.87020.6208716
CPSF6-MYF6chr1269633486chr128110163491HLA-B55:02QPDQMPPEA0.7960.82531120
CPSF6-MYF6chr1269633486chr128110163491HLA-B59:01QPDQMPPEA0.790.86451120
CPSF6-MYF6chr1269633486chr128110163491HLA-B56:02QPDQMPPEA0.59860.9691120
CPSF6-MYF6chr1269633486chr128110163491HLA-B51:05QPDQMPPEA0.57740.79161120
CPSF6-MYF6chr1269633486chr128110163491HLA-B35:09QPDQMPPEA0.48120.98781120
CPSF6-MYF6chr1269633486chr128110163491HLA-B67:01QPDQMPPEA0.44170.99431120
CPSF6-MYF6chr1269633486chr128110163491HLA-B78:02QPDQMPPEA0.41720.99181120
CPSF6-MYF6chr1269633486chr128110163491HLA-B82:02QPDQMPPEA0.3770.88191120

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Potential FusionNeoAntigen Information of CPSF6-MYF6 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 CPSF6-MYF6

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
924CRRRVQPDQMPPEACPSF6MYF6chr1269633486chr128110163491

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CPSF6-MYF6

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-B14:023BVN924CRRRVQPDQMPPEA-7.9962-8.1096
HLA-B14:023BVN924CRRRVQPDQMPPEA-5.70842-6.74372
HLA-B52:013W39924CRRRVQPDQMPPEA-6.83737-6.95077
HLA-B52:013W39924CRRRVQPDQMPPEA-4.4836-5.5189
HLA-A11:014UQ2924CRRRVQPDQMPPEA-10.0067-10.1201
HLA-A11:014UQ2924CRRRVQPDQMPPEA-9.03915-10.0745
HLA-A24:025HGA924CRRRVQPDQMPPEA-6.56204-6.67544
HLA-A24:025HGA924CRRRVQPDQMPPEA-5.42271-6.45801
HLA-B44:053DX8924CRRRVQPDQMPPEA-7.85648-8.89178
HLA-B44:053DX8924CRRRVQPDQMPPEA-5.3978-5.5112
HLA-A02:016TDR924CRRRVQPDQMPPEA-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CPSF6-MYF6

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
CPSF6-MYF6chr1269633486chr12811016341120QPDQMPPEAAACCAGACCAAATGCCCCCGGAAGCGG
CPSF6-MYF6chr1269633486chr1281101634716RRRVQPDQMGGCGAAGAGTTCAACCAGACCAAATGC
CPSF6-MYF6chr1269633486chr1281101634817RRVQPDQMPGAAGAGTTCAACCAGACCAAATGCCCC

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 CPSF6-MYF6

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
SARCCPSF6-MYF6chr1269633486ENST00000266679chr1281101634ENST00000228641TCGA-DX-A2J0-01A

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Potential target of CAR-T therapy development for CPSF6-MYF6

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 CPSF6-MYF6

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 CPSF6-MYF6

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