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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:BRWD1-DSCAM

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BRWD1-DSCAM
FusionPDB ID: 10342
FusionGDB2.0 ID: 10342
HgeneTgene
Gene symbol

BRWD1

DSCAM

Gene ID

54014

1826

Gene namebromodomain and WD repeat domain containing 1DS cell adhesion molecule
SynonymsC21orf107|DCAF19|N143|WDR9|WRD9CHD2|CHD2-42|CHD2-52
Cytomap

21q22.2

21q22.2

Type of geneprotein-codingprotein-coding
Descriptionbromodomain and WD repeat-containing protein 1WD repeat protein WDR9-form2WD repeat-containing protein 9transcriptional unit N143Down syndrome cell adhesion molecule
Modification date2020031320200313
UniProtAcc

Q9NSI6

Main function of 5'-partner protein: FUNCTION: May be a transcriptional activator. May be involved in chromatin remodeling (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape. {ECO:0000250, ECO:0000269|PubMed:21834987}.

Q8TD84

Main function of 5'-partner protein: FUNCTION: Cell adhesion molecule that plays a role in neuronal self-avoidance (PubMed:11453658). Promotes repulsion between specific neuronal processes of either the same cell or the same subtype of cells. Promotes both isoneuronal self-avoidance for creating an orderly neurite arborization in retinal rod bipolar cells and heteroneuronal self-avoidance to maintain mosaic spacing between AII amacrine cells (By similarity). Adhesion molecule that promotes lamina-specific synaptic connections in the retina: expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promotes synaptic connectivity via homophilic interactions (By similarity). {ECO:0000250|UniProtKB:E1C8P7, ECO:0000250|UniProtKB:Q4VA61, ECO:0000269|PubMed:11453658}.
Ensembl transtripts involved in fusion geneENST idsENST00000333229, ENST00000342449, 
ENST00000380800, ENST00000341322, 
ENST00000470108, 		ENST00000400454, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score28 X 28 X 10=784013 X 11 X 6=858
# samples 3215
** MAII scorelog2(32/7840*10)=-4.61470984411521
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(15/858*10)=-2.51601514700366
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: BRWD1 [Title/Abstract] AND DSCAM [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BRWD1 [Title/Abstract] AND DSCAM [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BRWD1(40641825)-DSCAM(41385313), # samples:2
Anticipated loss of major functional domain due to fusion event.BRWD1-DSCAM 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.
BRWD1-DSCAM 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
TgeneDSCAM

GO:0042327

positive regulation of phosphorylation

19196994

TgeneDSCAM

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/chr21:40641825/chr21:41385313)
- 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 BRWD1 (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 DSCAM (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)
ENST00000333229BRWD1chr2140641825-ENST00000400454DSCAMchr2141385313-424618582351905556
ENST00000342449BRWD1chr2140641825-ENST00000400454DSCAMchr2141385313-39971609791656525
ENST00000380800BRWD1chr2140641825-ENST00000400454DSCAMchr2141385313-4017162961676556
ENST00000333229BRWD1chr2140641824-ENST00000400454DSCAMchr2141385313-424618582351905556
ENST00000342449BRWD1chr2140641824-ENST00000400454DSCAMchr2141385313-39971609791656525
ENST00000380800BRWD1chr2140641824-ENST00000400454DSCAMchr2141385313-4017162961676556

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
ENST00000333229ENST00000400454BRWD1chr2140641825-DSCAMchr2141385313-0.0083493650.99165064
ENST00000342449ENST00000400454BRWD1chr2140641825-DSCAMchr2141385313-0.0076808410.99231917
ENST00000380800ENST00000400454BRWD1chr2140641825-DSCAMchr2141385313-0.0076418450.99235815
ENST00000333229ENST00000400454BRWD1chr2140641824-DSCAMchr2141385313-0.0083493650.99165064
ENST00000342449ENST00000400454BRWD1chr2140641824-DSCAMchr2141385313-0.0076808410.99231917
ENST00000380800ENST00000400454BRWD1chr2140641824-DSCAMchr2141385313-0.0076418450.99235815

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 BRWD1-DSCAM

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BRWD1chr2140641824DSCAMchr21413853131609510ITKGTKMKHYFNMVTSYICLHTLEWT
BRWD1chr2140641824DSCAMchr21413853131629541ITKGTKMKHYFNMVTSYICLHTLEWT
BRWD1chr2140641824DSCAMchr21413853131858541ITKGTKMKHYFNMVTSYICLHTLEWT
BRWD1chr2140641825DSCAMchr21413853131609510ITKGTKMKHYFNMVTSYICLHTLEWT
BRWD1chr2140641825DSCAMchr21413853131629541ITKGTKMKHYFNMVTSYICLHTLEWT
BRWD1chr2140641825DSCAMchr21413853131858541ITKGTKMKHYFNMVTSYICLHTLEWT

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Potential FusionNeoAntigen Information of BRWD1-DSCAM 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.
BRWD1-DSCAM_40641824_41385313.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)
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:02HYFNMVTSY0.94550.9103817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-A32:13HYFNMVTSY0.74140.9526817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:18HYFNMVTSY0.47460.7019817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:03HYFNMVTSY0.46890.7704817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:03KHYFNMVTSY0.94580.7528717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:18KHYFNMVTSY0.92850.6911717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:21YFNMVTSY0.96520.9113917
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:31HYFNMVTSY0.94770.7968817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:21HYFNMVTSY0.93780.8938817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:95HYFNMVTSY0.75140.5571817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:19HYFNMVTSY0.74620.522817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:67HYFNMVTSY0.69220.8793817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:80HYFNMVTSY0.69220.8793817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:29HYFNMVTSY0.69140.9011817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:27HYFNMVTSY0.66910.9058817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:10HYFNMVTSY0.63670.9077817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:46HYFNMVTSY0.61740.7423817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C12:16HYFNMVTSY0.52070.9703817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C03:14HYFNMVTSY0.50670.9627817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:05HYFNMVTSY0.42280.9161817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C04:10YFNMVTSYI0.03870.5863918
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C04:07YFNMVTSYI0.03780.6163918
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:46KHYFNMVTSY0.98040.7738717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:10KHYFNMVTSY0.97970.9167717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:80KHYFNMVTSY0.97630.8936717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:67KHYFNMVTSY0.97630.8936717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:17YFNMVTSY0.95220.9417917
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C14:02YFNMVTSY0.65860.9413917
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C14:03YFNMVTSY0.65860.9413917
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B35:23HYFNMVTSY0.94970.8817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B35:20HYFNMVTSY0.94230.8427817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:27HYFNMVTSY0.91240.8981817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:11HYFNMVTSY0.89680.8546817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:08HYFNMVTSY0.89570.8641817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:22HYFNMVTSY0.7740.6861817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:01HYFNMVTSY0.75780.5403817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B18:04HYFNMVTSY0.72950.8949817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:02HYFNMVTSY0.69220.8793817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:17HYFNMVTSY0.64690.952817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:13HYFNMVTSY0.61920.592817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B18:07HYFNMVTSY0.50820.8637817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B18:06HYFNMVTSY0.48440.8705817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B18:08HYFNMVTSY0.48010.7675817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B18:03HYFNMVTSY0.46230.875817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C12:02HYFNMVTSY0.39670.978817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C03:67HYFNMVTSY0.34690.9758817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C04:04YFNMVTSYI0.31930.6775918
BRWD1-DSCAMchr2140641824chr21413853131858HLA-A25:01HYFNMVTSY0.25750.8261817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B48:02HYFNMVTSY0.25440.8015817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:54HYFNMVTSY0.23450.8689817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:04YFNMVTSYI0.2150.8801918
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C06:06YFNMVTSYI0.07750.9858918
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C06:02HYFNMVTSY0.05130.9945817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C06:17HYFNMVTSY0.05130.9945817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C14:03YFNMVTSYI0.05040.9443918
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C14:02YFNMVTSYI0.05040.9443918
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:68HYFNMVTSY0.04160.6387817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C04:01YFNMVTSYI0.03780.6163918
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C18:01YFNMVTSYI0.03390.6474918
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C04:04HYFNMVTSY0.0320.7738817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C14:02HYFNMVTSY0.02020.9418817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C14:03HYFNMVTSY0.02020.9418817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C06:08HYFNMVTSY0.01870.9932817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C06:06HYFNMVTSY0.00980.9881817
BRWD1-DSCAMchr2140641824chr21413853131858HLA-C07:02KHYFNMVTSY0.97630.8936717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:54KHYFNMVTSY0.88360.8848717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B48:02KHYFNMVTSY0.79310.8577717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:68KHYFNMVTSY0.71510.6535717
BRWD1-DSCAMchr2140641824chr21413853131858HLA-B15:68MKHYFNMVTSY0.68040.6076617

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Potential FusionNeoAntigen Information of BRWD1-DSCAM 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 BRWD1-DSCAM

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
5933MKHYFNMVTSYICLBRWD1DSCAMchr2140641824chr21413853131858

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BRWD1-DSCAM

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-B14:023BVN5933MKHYFNMVTSYICL-7.15543-7.26883
HLA-B14:023BVN5933MKHYFNMVTSYICL-4.77435-5.80965
HLA-B52:013W395933MKHYFNMVTSYICL-6.80875-6.92215
HLA-B52:013W395933MKHYFNMVTSYICL-4.20386-5.23916
HLA-A11:014UQ25933MKHYFNMVTSYICL-7.5194-8.5547
HLA-A11:014UQ25933MKHYFNMVTSYICL-6.9601-7.0735
HLA-A24:025HGA5933MKHYFNMVTSYICL-7.52403-7.63743
HLA-A24:025HGA5933MKHYFNMVTSYICL-5.82433-6.85963
HLA-B27:056PYJ5933MKHYFNMVTSYICL-3.28285-4.31815
HLA-B44:053DX85933MKHYFNMVTSYICL-5.91172-6.94702
HLA-B44:053DX85933MKHYFNMVTSYICL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of BRWD1-DSCAM

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
BRWD1-DSCAMchr2140641824chr2141385313617MKHYFNMVTSYATGAAACATTATTTTAATATGGTGACCTCATAC
BRWD1-DSCAMchr2140641824chr2141385313717KHYFNMVTSYAAACATTATTTTAATATGGTGACCTCATAC
BRWD1-DSCAMchr2140641824chr2141385313817HYFNMVTSYCATTATTTTAATATGGTGACCTCATAC
BRWD1-DSCAMchr2140641824chr2141385313917YFNMVTSYTATTTTAATATGGTGACCTCATAC
BRWD1-DSCAMchr2140641824chr2141385313918YFNMVTSYITATTTTAATATGGTGACCTCATACATT

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 BRWD1-DSCAM

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
OVBRWD1-DSCAMchr2140641824ENST00000333229chr2141385313ENST00000400454TCGA-24-2289

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Potential target of CAR-T therapy development for BRWD1-DSCAM

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 BRWD1-DSCAM

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 BRWD1-DSCAM

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