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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:MYO6-ADCK4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MYO6-ADCK4
FusionPDB ID: 56742
FusionGDB2.0 ID: 56742
HgeneTgene
Gene symbol

MYO6

ADCK4

Gene ID

4646

79934

Gene namemyosin VIcoenzyme Q8B
SynonymsDFNA22|DFNB37ADCK4|NPHS9
Cytomap

6q14.1

19q13.2

Type of geneprotein-codingprotein-coding
Descriptionunconventional myosin-VIunconventional myosin-6atypical kinase COQ8B, mitochondrialaarF domain containing kinase 4aarF domain-containing protein kinase 4coenzyme Q protein 8B
Modification date2020031320200313
UniProtAcc

Q9UM54

Main function of 5'-partner protein: FUNCTION: Myosins are actin-based motor molecules with ATPase activity (By similarity). Unconventional myosins serve in intracellular movements (By similarity). Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments (PubMed:10519557). Has slow rate of actin-activated ADP release due to weak ATP binding (By similarity). Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration (By similarity). Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway (PubMed:16507995). Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells (PubMed:11447109). May act as a regulator of F-actin dynamics (By similarity). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). May play a role in transporting DAB2 from the plasma membrane to specific cellular targets (By similarity). May play a role in the extension and network organization of neurites (By similarity). Required for structural integrity of inner ear hair cells (By similarity). Modulates RNA polymerase II-dependent transcription (PubMed:16949370). {ECO:0000250|UniProtKB:Q29122, ECO:0000250|UniProtKB:Q64331, ECO:0000269|PubMed:10519557, ECO:0000269|PubMed:11447109, ECO:0000269|PubMed:16507995, ECO:0000269|PubMed:16949370, ECO:0000269|PubMed:29467281}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000369975, ENST00000369977, 
ENST00000369981, ENST00000369985, 
ENST00000462633, 
ENST00000243583, 
ENST00000324464, ENST00000450541, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 13 X 10=19504 X 3 X 4=48
# samples 224
** MAII scorelog2(22/1950*10)=-3.14789869511231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MYO6 [Title/Abstract] AND ADCK4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MYO6 [Title/Abstract] AND ADCK4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MYO6(76618344)-ADCK4(41216041), # samples:1
Anticipated loss of major functional domain due to fusion event.MYO6-ADCK4 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.
MYO6-ADCK4 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.
MYO6-ADCK4 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.
MYO6-ADCK4 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
HgeneMYO6

GO:0030330

DNA damage response, signal transduction by p53 class mediator

16507995

TgeneADCK4

GO:0006468

protein phosphorylation

27499294



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/chr6:76618344/chr19:41216041)
- 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 MYO6 (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 ADCK4 (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)
ENST00000369981MYO6chr676618344+ENST00000324464ADCK4chr1941216041-5573372127950661595
ENST00000369981MYO6chr676618344+ENST00000450541ADCK4chr1941216041-5450372127949431554
ENST00000369981MYO6chr676618344+ENST00000243583ADCK4chr1941216041-5449372127949431554
ENST00000369985MYO6chr676618344+ENST00000324464ADCK4chr1941216041-5457360526249501562
ENST00000369985MYO6chr676618344+ENST00000450541ADCK4chr1941216041-5334360526248271521
ENST00000369985MYO6chr676618344+ENST00000243583ADCK4chr1941216041-5333360526248271521
ENST00000369977MYO6chr676618344+ENST00000324464ADCK4chr1941216041-5403355113948961585
ENST00000369977MYO6chr676618344+ENST00000450541ADCK4chr1941216041-5280355113947731544
ENST00000369977MYO6chr676618344+ENST00000243583ADCK4chr1941216041-5279355113947731544
ENST00000369975MYO6chr676618344+ENST00000324464ADCK4chr1941216041-522033682547131562
ENST00000369975MYO6chr676618344+ENST00000450541ADCK4chr1941216041-509733682545901521
ENST00000369975MYO6chr676618344+ENST00000243583ADCK4chr1941216041-509633682545901521

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
ENST00000369981ENST00000324464MYO6chr676618344+ADCK4chr1941216041-0.0009939390.9990061
ENST00000369981ENST00000450541MYO6chr676618344+ADCK4chr1941216041-0.0015787890.9984212
ENST00000369981ENST00000243583MYO6chr676618344+ADCK4chr1941216041-0.0015884210.99841154
ENST00000369985ENST00000324464MYO6chr676618344+ADCK4chr1941216041-0.0012519040.99874806
ENST00000369985ENST00000450541MYO6chr676618344+ADCK4chr1941216041-0.0010000390.999
ENST00000369985ENST00000243583MYO6chr676618344+ADCK4chr1941216041-0.0010067130.99899334
ENST00000369977ENST00000324464MYO6chr676618344+ADCK4chr1941216041-0.0014535030.9985464
ENST00000369977ENST00000450541MYO6chr676618344+ADCK4chr1941216041-0.0010098780.9989901
ENST00000369977ENST00000243583MYO6chr676618344+ADCK4chr1941216041-0.0010159650.99898404
ENST00000369975ENST00000324464MYO6chr676618344+ADCK4chr1941216041-0.0010262920.9989737
ENST00000369975ENST00000450541MYO6chr676618344+ADCK4chr1941216041-0.0008046230.9991954
ENST00000369975ENST00000243583MYO6chr676618344+ADCK4chr1941216041-0.0008098610.99919015

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 MYO6-ADCK4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MYO6chr676618344ADCK4chr194121604133681114ETEQRAPKSVTDYGLAVGLGLGVLAE
MYO6chr676618344ADCK4chr194121604135511137ETEQRAPKSVTDYGLAVGLGLGVLAE
MYO6chr676618344ADCK4chr194121604136051114ETEQRAPKSVTDYGLAVGLGLGVLAE
MYO6chr676618344ADCK4chr194121604137211147ETEQRAPKSVTDYGLAVGLGLGVLAE

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Potential FusionNeoAntigen Information of MYO6-ADCK4 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.
MYO6-ADCK4_76618344_41216041.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)
MYO6-ADCK4chr676618344chr19412160413368HLA-A02:21SVTDYGLAV0.96130.5437817
MYO6-ADCK4chr676618344chr19412160413368HLA-B47:01TDYGLAVGL0.27680.69371019
MYO6-ADCK4chr676618344chr19412160413368HLA-C05:09VTDYGLAV10.9521917
MYO6-ADCK4chr676618344chr19412160413368HLA-C08:15VTDYGLAV0.99990.9711917
MYO6-ADCK4chr676618344chr19412160413368HLA-C08:13VTDYGLAV0.91730.9866917
MYO6-ADCK4chr676618344chr19412160413368HLA-C08:04VTDYGLAV0.91730.9866917
MYO6-ADCK4chr676618344chr19412160413368HLA-C04:06SVTDYGLAV0.99490.8296817
MYO6-ADCK4chr676618344chr19412160413368HLA-C15:06SVTDYGLAV0.99370.7707817
MYO6-ADCK4chr676618344chr19412160413368HLA-C03:19SVTDYGLAV0.89970.986817
MYO6-ADCK4chr676618344chr19412160413368HLA-C08:04SVTDYGLAV0.75590.9185817
MYO6-ADCK4chr676618344chr19412160413368HLA-C08:13SVTDYGLAV0.75590.9185817
MYO6-ADCK4chr676618344chr19412160413368HLA-C02:06SVTDYGLAV0.62850.9071817
MYO6-ADCK4chr676618344chr19412160413368HLA-C08:03SVTDYGLAV0.55930.9551817
MYO6-ADCK4chr676618344chr19412160413368HLA-C05:01VTDYGLAV10.9521917
MYO6-ADCK4chr676618344chr19412160413368HLA-C04:03VTDYGLAV10.8317917
MYO6-ADCK4chr676618344chr19412160413368HLA-C08:02VTDYGLAV0.99990.9711917
MYO6-ADCK4chr676618344chr19412160413368HLA-C15:02SVTDYGLAV0.99620.7153817
MYO6-ADCK4chr676618344chr19412160413368HLA-C15:05SVTDYGLAV0.99560.7767817
MYO6-ADCK4chr676618344chr19412160413368HLA-A69:01SVTDYGLAV0.98440.6362817
MYO6-ADCK4chr676618344chr19412160413368HLA-A02:06SVTDYGLAV0.96130.5437817
MYO6-ADCK4chr676618344chr19412160413368HLA-C03:06SVTDYGLAV0.91840.9849817
MYO6-ADCK4chr676618344chr19412160413368HLA-C08:01SVTDYGLAV0.55930.9551817
MYO6-ADCK4chr676618344chr19412160413368HLA-C17:01SVTDYGLAV0.31360.8204817
MYO6-ADCK4chr676618344chr19412160413368HLA-C01:02RAPKSVTDYGL0.99420.9057415

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Potential FusionNeoAntigen Information of MYO6-ADCK4 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 MYO6-ADCK4

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
6746PKSVTDYGLAVGLGMYO6ADCK4chr676618344chr19412160413368

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MYO6-ADCK4

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-B14:023BVN6746PKSVTDYGLAVGLG-7.9962-8.1096
HLA-B14:023BVN6746PKSVTDYGLAVGLG-5.70842-6.74372
HLA-B52:013W396746PKSVTDYGLAVGLG-6.83737-6.95077
HLA-B52:013W396746PKSVTDYGLAVGLG-4.4836-5.5189
HLA-A11:014UQ26746PKSVTDYGLAVGLG-10.0067-10.1201
HLA-A11:014UQ26746PKSVTDYGLAVGLG-9.03915-10.0745
HLA-A24:025HGA6746PKSVTDYGLAVGLG-6.56204-6.67544
HLA-A24:025HGA6746PKSVTDYGLAVGLG-5.42271-6.45801
HLA-B44:053DX86746PKSVTDYGLAVGLG-7.85648-8.89178
HLA-B44:053DX86746PKSVTDYGLAVGLG-5.3978-5.5112
HLA-A02:016TDR6746PKSVTDYGLAVGLG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of MYO6-ADCK4

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
MYO6-ADCK4chr676618344chr19412160411019TDYGLAVGLCTGATTATGGACTGGCTGTGGGCTTGG
MYO6-ADCK4chr676618344chr1941216041415RAPKSVTDYGLGTGCTCCAAAGTCTGTTACTGATTATGGACTGG
MYO6-ADCK4chr676618344chr1941216041817SVTDYGLAVCTGTTACTGATTATGGACTGGCTGTGG
MYO6-ADCK4chr676618344chr1941216041917VTDYGLAVTTACTGATTATGGACTGGCTGTGG

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 MYO6-ADCK4

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
OVMYO6-ADCK4chr676618344ENST00000369975chr1941216041ENST00000243583TCGA-25-1877

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Potential target of CAR-T therapy development for MYO6-ADCK4

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 MYO6-ADCK4

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 MYO6-ADCK4

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