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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-GNAI3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BRWD1-GNAI3
FusionPDB ID: 10346
FusionGDB2.0 ID: 10346
HgeneTgene
Gene symbol

BRWD1

GNAI3

Gene ID

54014

2773

Gene namebromodomain and WD repeat domain containing 1G protein subunit alpha i3
SynonymsC21orf107|DCAF19|N143|WDR9|WRD987U6|ARCND1
Cytomap

21q22.2

1p13.3

Type of geneprotein-codingprotein-coding
Descriptionbromodomain and WD repeat-containing protein 1WD repeat protein WDR9-form2WD repeat-containing protein 9transcriptional unit N143guanine nucleotide-binding protein G(i) subunit alphag(i) alpha-3guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3guanine nucleotide-binding protein G(k) subunit alpha
Modification date2020031320200322
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}.

P08754

Main function of 5'-partner protein: FUNCTION: Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:8774883, PubMed:18434541, PubMed:19478087). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:19478087). Stimulates the activity of receptor-regulated K(+) channels (PubMed:2535845). The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division (PubMed:17635935). {ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:2535845, ECO:0000269|PubMed:8774883}.
Ensembl transtripts involved in fusion geneENST idsENST00000333229, ENST00000342449, 
ENST00000380800, ENST00000341322, 
ENST00000470108, 
ENST00000369851, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score28 X 28 X 10=784033 X 8 X 14=3696
# samples 3235
** MAII scorelog2(32/7840*10)=-4.61470984411521
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(35/3696*10)=-3.40053792958373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: BRWD1 [Title/Abstract] AND GNAI3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BRWD1 [Title/Abstract] AND GNAI3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BRWD1(40670357)-GNAI3(110116358), # samples:1
Anticipated loss of major functional domain due to fusion event.BRWD1-GNAI3 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-GNAI3 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-GNAI3 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-GNAI3 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
TgeneGNAI3

GO:0007193

adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway

19478087

TgeneGNAI3

GO:0007212

dopamine receptor signaling pathway

19478087

TgeneGNAI3

GO:0046039

GTP metabolic process

19478087

TgeneGNAI3

GO:0051301

cell division

17635935



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/chr21:40670357/chr1:110116358)
- 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 GNAI3 (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)
ENST00000333229BRWD1chr2140670357-ENST00000369851GNAI3chr1110116358+36556772351623462
ENST00000342449BRWD1chr2140670357-ENST00000369851GNAI3chr1110116358+3406428791374431
ENST00000380800BRWD1chr2140670357-ENST00000369851GNAI3chr1110116358+342644861394462

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
ENST00000333229ENST00000369851BRWD1chr2140670357-GNAI3chr1110116358+0.0002034610.99979657
ENST00000342449ENST00000369851BRWD1chr2140670357-GNAI3chr1110116358+0.0001863990.9998136
ENST00000380800ENST00000369851BRWD1chr2140670357-GNAI3chr1110116358+0.0001849750.99981505

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-GNAI3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BRWD1chr2140670357GNAI3chr1110116358428116LGAGRQSLLRTAKGAGESGKSTIVKQ
BRWD1chr2140670357GNAI3chr1110116358448147LGAGRQSLLRTAKGAGESGKSTIVKQ
BRWD1chr2140670357GNAI3chr1110116358677147LGAGRQSLLRTAKGAGESGKSTIVKQ

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Potential FusionNeoAntigen Information of BRWD1-GNAI3 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-GNAI3_40670357_110116358.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-GNAI3chr2140670357chr1110116358677HLA-A11:03RTAKGAGESGK0.99890.5059920

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Potential FusionNeoAntigen Information of BRWD1-GNAI3 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-GNAI3_40670357_110116358.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-GNAI3chr2140670357chr1110116358677DRB1-0804RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-0804GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-0820RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-0820GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-0828RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-0831RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-0831GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1104RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1104GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1106RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1106GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1125RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1135RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1135GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1137RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1138RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1138GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1141RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1142RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1143RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1143GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1144RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1144GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1146RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1146GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1147RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1147GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1150RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1150GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1154RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1154GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1154AGRQSLLRTAKGAGE217
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1156RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1156GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1158RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1158GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1160RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1160GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1167RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1177RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1177GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1178RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1178GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1183RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1183GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1184RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1184GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1188RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1188GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1189RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1193RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1307RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1311RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1311GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1318RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1342RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1342GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1347RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1415RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1415GRQSLLRTAKGAGES318
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1473RQSLLRTAKGAGESG419
BRWD1-GNAI3chr2140670357chr1110116358677DRB1-1484RQSLLRTAKGAGESG419

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Fusion breakpoint peptide structures of BRWD1-GNAI3

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
8762SLLRTAKGAGESGKBRWD1GNAI3chr2140670357chr1110116358677

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BRWD1-GNAI3

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-B14:023BVN8762SLLRTAKGAGESGK-4.62424-5.65954
HLA-B14:023BVN8762SLLRTAKGAGESGK-4.1114-4.2248
HLA-B52:013W398762SLLRTAKGAGESGK-6.8001-6.9135
HLA-B52:013W398762SLLRTAKGAGESGK-6.46104-7.49634
HLA-A24:025HGA8762SLLRTAKGAGESGK-9.1447-9.2581
HLA-A24:025HGA8762SLLRTAKGAGESGK-6.01279-7.04809
HLA-B44:053DX88762SLLRTAKGAGESGK-5.02862-5.14202
HLA-B44:053DX88762SLLRTAKGAGESGK-4.60714-5.64244

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Vaccine Design for the FusionNeoAntigens of BRWD1-GNAI3

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-GNAI3chr2140670357chr1110116358920RTAKGAGESGKGTACAGCAAAAGGTGCTGGAGAATCTGGTAAAA

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-GNAI3chr2140670357chr1110116358217AGRQSLLRTAKGAGECAGGAAGGCAGTCTTTGCTACGTACAGCAAAAGGTGCTGGAGAAT
BRWD1-GNAI3chr2140670357chr1110116358318GRQSLLRTAKGAGESGAAGGCAGTCTTTGCTACGTACAGCAAAAGGTGCTGGAGAATCTG
BRWD1-GNAI3chr2140670357chr1110116358419RQSLLRTAKGAGESGGGCAGTCTTTGCTACGTACAGCAAAAGGTGCTGGAGAATCTGGTA

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Information of the samples that have these potential fusion neoantigens of BRWD1-GNAI3

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
BRCABRWD1-GNAI3chr2140670357ENST00000333229chr1110116358ENST00000369851TCGA-D8-A1XT

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Potential target of CAR-T therapy development for BRWD1-GNAI3

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-GNAI3

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-GNAI3

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