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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-CHMP1A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BRWD1-CHMP1A
FusionPDB ID: 10340
FusionGDB2.0 ID: 10340
HgeneTgene
Gene symbol

BRWD1

CHMP1A

Gene ID

54014

5119

Gene namebromodomain and WD repeat domain containing 1charged multivesicular body protein 1A
SynonymsC21orf107|DCAF19|N143|WDR9|WRD9CHMP1|PCH8|PCOLN3|PRSM1|VPS46-1|VPS46A
Cytomap

21q22.2

16q24.3

Type of geneprotein-codingprotein-coding
Descriptionbromodomain and WD repeat-containing protein 1WD repeat protein WDR9-form2WD repeat-containing protein 9transcriptional unit N143charged multivesicular body protein 1acharged multivesicular body protein 1/chromatin modifying protein 1chromatin modifying protein 1Aprocollagen (type III) N-endopeptidaseprotease, metallo, 1, 33kDvacuolar protein sorting-associated protein 46-1
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}.

Q9HD42

Main function of 5'-partner protein: FUNCTION: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing. {ECO:0000269|PubMed:11559747, ECO:0000269|PubMed:11559748, ECO:0000269|PubMed:19129479, ECO:0000269|PubMed:23045692}.
Ensembl transtripts involved in fusion geneENST idsENST00000333229, ENST00000342449, 
ENST00000380800, ENST00000341322, 
ENST00000470108, 
ENST00000547614, 
ENST00000397901, ENST00000535997, 
ENST00000550102, ENST00000253475, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score28 X 28 X 10=784045 X 11 X 21=10395
# samples 3248
** MAII scorelog2(32/7840*10)=-4.61470984411521
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(48/10395*10)=-4.43671154213721
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: BRWD1 [Title/Abstract] AND CHMP1A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BRWD1 [Title/Abstract] AND CHMP1A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BRWD1(40670358)-CHMP1A(89713739), # samples:1
Anticipated loss of major functional domain due to fusion event.BRWD1-CHMP1A 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-CHMP1A 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-CHMP1A 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.
BRWD1-CHMP1A 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.
BRWD1-CHMP1A seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
BRWD1-CHMP1A seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
BRWD1-CHMP1A seems lost the major protein functional domain in Hgene 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
TgeneCHMP1A

GO:0007076

mitotic chromosome condensation

11559747

TgeneCHMP1A

GO:0016192

vesicle-mediated transport

11559748

TgeneCHMP1A

GO:0016458

gene silencing

11559747

TgeneCHMP1A

GO:0045892

negative regulation of transcription, DNA-templated

11559747



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/chr21:40670358/chr16:89713739)
- 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 CHMP1A (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)
ENST00000333229BRWD1chr2140670358-ENST00000253475CHMP1Achr1689713739-26446772351167310
ENST00000342449BRWD1chr2140670358-ENST00000253475CHMP1Achr1689713739-239542879918279
ENST00000380800BRWD1chr2140670358-ENST00000253475CHMP1Achr1689713739-24154486938310

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
ENST00000333229ENST00000253475BRWD1chr2140670358-CHMP1Achr1689713739-0.31443390.68556607
ENST00000342449ENST00000253475BRWD1chr2140670358-CHMP1Achr1689713739-0.329835270.6701647
ENST00000380800ENST00000253475BRWD1chr2140670358-CHMP1Achr1689713739-0.328833220.6711668

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-CHMP1A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BRWD1chr2140670358CHMP1Achr1689713739428116LGAGRQSLLRTAKGDQEYGPGDQSPG
BRWD1chr2140670358CHMP1Achr1689713739448147LGAGRQSLLRTAKGDQEYGPGDQSPG
BRWD1chr2140670358CHMP1Achr1689713739677147LGAGRQSLLRTAKGDQEYGPGDQSPG

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Potential FusionNeoAntigen Information of BRWD1-CHMP1A 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-CHMP1A_40670358_89713739.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-CHMP1Achr2140670358chr1689713739677HLA-B15:25RTAKGDQEY0.99630.8596918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:01RTAKGDQEY0.99610.8215918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:17RTAKGDQEY0.99050.8347918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B58:01RTAKGDQEY0.95810.9366918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:16RTAKGDQEY0.94570.7566918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B58:02RTAKGDQEY0.93970.9124918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-A32:13RTAKGDQEY0.36870.8061918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:01LLRTAKGDQEY10.8642718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:25LLRTAKGDQEY0.99870.9106718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:07RTAKGDQEY0.98250.593918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:05RTAKGDQEY0.92480.8411918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C15:04RTAKGDQEY0.78260.8342918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C03:14RTAKGDQEY0.59060.9531918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:07LLRTAKGDQEY0.99980.6418718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:39RTAKGDQEY0.99620.7521918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:27RTAKGDQEY0.99620.8246918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:34RTAKGDQEY0.99610.8215918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:33RTAKGDQEY0.99610.8215918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:125RTAKGDQEY0.99610.8215918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:135RTAKGDQEY0.99560.8457918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:50RTAKGDQEY0.99370.7801918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:12RTAKGDQEY0.98770.7814918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B57:04RTAKGDQEY0.98540.7211918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:24RTAKGDQEY0.98480.8118918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:35RTAKGDQEY0.98470.8094918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B58:06RTAKGDQEY0.96390.8577918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:53RTAKGDQEY0.93810.7969918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:20RTAKGDQEY0.9310.9113918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B35:28RTAKGDQEY0.89170.9281918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B57:02RTAKGDQEY0.85650.8843918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C15:09RTAKGDQEY0.78260.8342918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:54RTAKGDQEY0.6050.7648918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C03:02RTAKGDQEY0.55190.9374918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C16:01RTAKGDQEY0.54890.9476918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C16:04RTAKGDQEY0.48610.9428918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C16:02RTAKGDQEY0.350.987918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C12:02RTAKGDQEY0.15990.912918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C02:10RTAKGDQEY0.1260.9546918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-C02:02RTAKGDQEY0.1260.9546918
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:125LLRTAKGDQEY10.8642718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:27LLRTAKGDQEY10.872718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:33LLRTAKGDQEY10.8642718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:135LLRTAKGDQEY10.8855718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:34LLRTAKGDQEY10.8642718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:50LLRTAKGDQEY0.99990.8663718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:35LLRTAKGDQEY0.99980.842718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:12LLRTAKGDQEY0.99960.8724718
BRWD1-CHMP1Achr2140670358chr1689713739677HLA-B15:39LLRTAKGDQEY0.99860.8201718

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Potential FusionNeoAntigen Information of BRWD1-CHMP1A 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.
BRWD1-CHMP1A_40670358_89713739.msa

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)
BRWD1-CHMP1Achr2140670358chr1689713739677DRB1-1154RQSLLRTAKGDQEYG419

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Fusion breakpoint peptide structures of BRWD1-CHMP1A

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
8763SLLRTAKGDQEYGPBRWD1CHMP1Achr2140670358chr1689713739677

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BRWD1-CHMP1A

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-B14:023BVN8763SLLRTAKGDQEYGP-5.42908-5.54248
HLA-B14:023BVN8763SLLRTAKGDQEYGP-5.06008-6.09538
HLA-B52:013W398763SLLRTAKGDQEYGP-9.1987-9.3121
HLA-B52:013W398763SLLRTAKGDQEYGP-7.53083-8.56613
HLA-A11:014UQ28763SLLRTAKGDQEYGP-8.87547-8.98887
HLA-A24:025HGA8763SLLRTAKGDQEYGP-7.78065-7.89405
HLA-A24:025HGA8763SLLRTAKGDQEYGP-7.11918-8.15448
HLA-B27:056PYJ8763SLLRTAKGDQEYGP-7.64943-7.76283
HLA-B27:056PYJ8763SLLRTAKGDQEYGP-6.50173-7.53703
HLA-B44:053DX88763SLLRTAKGDQEYGP-7.26947-7.38287
HLA-B44:053DX88763SLLRTAKGDQEYGP-6.09544-7.13074

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Vaccine Design for the FusionNeoAntigens of BRWD1-CHMP1A

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-CHMP1Achr2140670358chr1689713739718LLRTAKGDQEYTGCTACGTACAGCAAAAGGTGACCAAGAATATG
BRWD1-CHMP1Achr2140670358chr1689713739918RTAKGDQEYGTACAGCAAAAGGTGACCAAGAATATG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
BRWD1-CHMP1Achr2140670358chr1689713739419RQSLLRTAKGDQEYGGGCAGTCTTTGCTACGTACAGCAAAAGGTGACCAAGAATATGGCC

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Information of the samples that have these potential fusion neoantigens of BRWD1-CHMP1A

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
Non-CancerBRWD1-CHMP1Achr2140670358ENST00000333229chr1689713739ENST00000253475TCGA-IN-8462-11A

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Potential target of CAR-T therapy development for BRWD1-CHMP1A

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-CHMP1A

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-CHMP1A

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