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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:ROCK1-CHD2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ROCK1-CHD2
FusionPDB ID: 75301
FusionGDB2.0 ID: 75301
HgeneTgene
Gene symbol

ROCK1

CHD2

Gene ID

6093

1826

Gene nameRho associated coiled-coil containing protein kinase 1DS cell adhesion molecule
SynonymsP160ROCK|ROCK-ICHD2|CHD2-42|CHD2-52
Cytomap

18q11.1

21q22.2

Type of geneprotein-codingprotein-coding
Descriptionrho-associated protein kinase 1p160 ROCK-1renal carcinoma antigen NY-REN-35Down syndrome cell adhesion molecule
Modification date2020032220200313
UniProtAcc.

O14647

Main function of 5'-partner protein: FUNCTION: DNA-binding helicase that specifically binds to the promoter of target genes, leading to chromatin remodeling, possibly by promoting deposition of histone H3.3. Involved in myogenesis via interaction with MYOD1: binds to myogenic gene regulatory sequences and mediates incorporation of histone H3.3 prior to the onset of myogenic gene expression, promoting their expression (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000399799, ENST00000420239, 
ENST00000536619, ENST00000554122, 
ENST00000394196, ENST00000557381, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score24 X 16 X 12=460822 X 16 X 8=2816
# samples 3121
** MAII scorelog2(31/4608*10)=-3.89380059616807
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/2816*10)=-3.74518610097117
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ROCK1 [Title/Abstract] AND CHD2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ROCK1 [Title/Abstract] AND CHD2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ROCK1(18600111)-CHD2(93510554), # samples:2
Anticipated loss of major functional domain due to fusion event.ROCK1-CHD2 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.
ROCK1-CHD2 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.
ROCK1-CHD2 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.
ROCK1-CHD2 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
HgeneROCK1

GO:0006468

protein phosphorylation

23093407

HgeneROCK1

GO:0007159

leukocyte cell-cell adhesion

12082081

HgeneROCK1

GO:0018105

peptidyl-serine phosphorylation

18573880

HgeneROCK1

GO:0022614

membrane to membrane docking

12082081

HgeneROCK1

GO:0030334

regulation of cell migration

23093407

HgeneROCK1

GO:0032091

negative regulation of protein binding

18573880

HgeneROCK1

GO:0032956

regulation of actin cytoskeleton organization

25911094

HgeneROCK1

GO:0050900

leukocyte migration

12082081

HgeneROCK1

GO:0050901

leukocyte tethering or rolling

12082081

HgeneROCK1

GO:0070507

regulation of microtubule cytoskeleton organization

23093407

TgeneCHD2

GO:0042327

positive regulation of phosphorylation

19196994

TgeneCHD2

GO:0048842

positive regulation of axon extension involved in axon guidance

18585357



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/chr18:18600111/chr15:93510554)
- 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 ROCK1 (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 CHD2 (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)
ENST00000399799ROCK1chr1818600111-ENST00000394196CHD2chr1593510554+9091230289957881629
ENST00000399799ROCK1chr1818600111-ENST00000557381CHD2chr1593510554+7359230289955211540

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
ENST00000399799ENST00000394196ROCK1chr1818600111-CHD2chr1593510554+0.001080710.99891937
ENST00000399799ENST00000557381ROCK1chr1818600111-CHD2chr1593510554+0.0011410210.9988589

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 ROCK1-CHD2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ROCK1chr1818600111CHD2chr15935105542302467NEMQLKDEMEQKCRFEFWEDFEEDHG

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Potential FusionNeoAntigen Information of ROCK1-CHD2 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.
ROCK1-CHD2_18600111_93510554.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)
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:03MEQKCRFEF0.99830.9274817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:03DEMEQKCRF0.9980.9009615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:04CRFEFWEDF0.99770.82431221
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:01DEMEQKCRF0.99760.7799615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:02CRFEFWEDF0.99730.82311221
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:01MEQKCRFEF0.99570.8814817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B47:01MEQKCRFEF0.98850.5096817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:03MEQKCRFEFW0.99790.9398818
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:05KCRFEFWEDF0.98490.93241121
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:02KCRFEFWEDF0.98380.79251121
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:04KCRFEFWEDF0.98220.78421121
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:03KDEMEQKCRF0.96780.9168515
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:07KCRFEFWEDF0.88070.6211121
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:03DEMEQKCRFEF0.99970.9162617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:01DEMEQKCRFEF0.99830.7869617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:03KCRFEFWEDF0.71730.93681121
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:26MEQKCRFEF0.99830.9274817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:13MEQKCRFEF0.99830.9274817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:07MEQKCRFEF0.99830.9274817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:07DEMEQKCRF0.99820.7361615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:04DEMEQKCRF0.99820.8116615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:26DEMEQKCRF0.9980.9009615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:13DEMEQKCRF0.9980.9009615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:07DEMEQKCRF0.9980.9009615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:05DEMEQKCRF0.99760.7799615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:08DEMEQKCRF0.99750.6641615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:08CRFEFWEDF0.99720.88741221
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:06DEMEQKCRF0.9970.7707615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:03DEMEQKCRF0.99640.7646615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:08MEQKCRFEF0.99640.8283817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:05MEQKCRFEF0.99570.8814817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:06MEQKCRFEF0.99570.8812817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:03MEQKCRFEF0.9950.8701817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:04MEQKCRFEF0.9940.8898817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:11MEQKCRFEF0.96360.9311817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:11DEMEQKCRF0.96240.6441615
ROCK1-CHD2chr1818600111chr15935105542302HLA-B15:24EQKCRFEFW0.8890.8051918
ROCK1-CHD2chr1818600111chr15935105542302HLA-B48:02MEQKCRFEF0.5660.8798817
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:13MEQKCRFEFW0.99790.9398818
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:26MEQKCRFEFW0.99790.9398818
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:07MEQKCRFEFW0.99790.9398818
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:08KCRFEFWEDF0.98290.87071121
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:26KDEMEQKCRF0.96780.9168515
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:13KDEMEQKCRF0.96780.9168515
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:07KDEMEQKCRF0.96780.9168515
ROCK1-CHD2chr1818600111chr15935105542302HLA-B27:09KCRFEFWEDF0.91410.90251121
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:13DEMEQKCRFEF0.99970.9162617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:07DEMEQKCRFEF0.99970.9162617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B44:26DEMEQKCRFEF0.99970.9162617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:08DEMEQKCRFEF0.99870.7449617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:04DEMEQKCRFEF0.99860.8054617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:07DEMEQKCRFEF0.99860.7508617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:06DEMEQKCRFEF0.99850.7905617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:05DEMEQKCRFEF0.99830.7869617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:03DEMEQKCRFEF0.99760.7798617
ROCK1-CHD2chr1818600111chr15935105542302HLA-B18:11DEMEQKCRFEF0.99480.7148617

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Potential FusionNeoAntigen Information of ROCK1-CHD2 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 ROCK1-CHD2

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
1072DEMEQKCRFEFWEDROCK1CHD2chr1818600111chr15935105542302

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ROCK1-CHD2

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-B14:023BVN1072DEMEQKCRFEFWED-7.15543-7.26883
HLA-B14:023BVN1072DEMEQKCRFEFWED-4.77435-5.80965
HLA-B52:013W391072DEMEQKCRFEFWED-6.80875-6.92215
HLA-B52:013W391072DEMEQKCRFEFWED-4.20386-5.23916
HLA-A11:014UQ21072DEMEQKCRFEFWED-7.5194-8.5547
HLA-A11:014UQ21072DEMEQKCRFEFWED-6.9601-7.0735
HLA-A24:025HGA1072DEMEQKCRFEFWED-7.52403-7.63743
HLA-A24:025HGA1072DEMEQKCRFEFWED-5.82433-6.85963
HLA-B27:056PYJ1072DEMEQKCRFEFWED-3.28285-4.31815
HLA-B44:053DX81072DEMEQKCRFEFWED-5.91172-6.94702
HLA-B44:053DX81072DEMEQKCRFEFWED-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ROCK1-CHD2

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
ROCK1-CHD2chr1818600111chr15935105541121KCRFEFWEDFGTGCAGGTTTGAATTTTGGGAAGATTTTGA
ROCK1-CHD2chr1818600111chr15935105541221CRFEFWEDFCAGGTTTGAATTTTGGGAAGATTTTGA
ROCK1-CHD2chr1818600111chr1593510554515KDEMEQKCRFAGATGAAATGGAGCAGAAGTGCAGGTTTGA
ROCK1-CHD2chr1818600111chr1593510554615DEMEQKCRFTGAAATGGAGCAGAAGTGCAGGTTTGA
ROCK1-CHD2chr1818600111chr1593510554617DEMEQKCRFEFTGAAATGGAGCAGAAGTGCAGGTTTGAATTTTG
ROCK1-CHD2chr1818600111chr1593510554817MEQKCRFEFGGAGCAGAAGTGCAGGTTTGAATTTTG
ROCK1-CHD2chr1818600111chr1593510554818MEQKCRFEFWGGAGCAGAAGTGCAGGTTTGAATTTTGGGA
ROCK1-CHD2chr1818600111chr1593510554918EQKCRFEFWGCAGAAGTGCAGGTTTGAATTTTGGGA

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 ROCK1-CHD2

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
ESCAROCK1-CHD2chr1818600111ENST00000399799chr1593510554ENST00000394196TCGA-LN-A4MQ

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Potential target of CAR-T therapy development for ROCK1-CHD2

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 ROCK1-CHD2

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 ROCK1-CHD2

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