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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:BRMS1L-NPAS3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BRMS1L-NPAS3
FusionPDB ID: 10315
FusionGDB2.0 ID: 10315
HgeneTgene
Gene symbol

BRMS1L

NPAS3

Gene ID

84312

64067

Gene nameBRMS1 like transcriptional repressorneuronal PAS domain protein 3
SynonymsBRMS1MOP6|PASD6|bHLHe12
Cytomap

14q13.2

14q13.1

Type of geneprotein-codingprotein-coding
Descriptionbreast cancer metastasis-suppressor 1-like proteinBRMS1-homolog protein p40BRMS1-like protein p40breast cancer metastasis-suppressor 1breast cancer metastasis-suppressor 1 likeneuronal PAS domain-containing protein 3PAS domain-containing protein 6basic-helix-loop-helix-PAS protein MOP6class E basic helix-loop-helix protein 12member of PAS protein 6neuronal PAS3
Modification date2020031320200313
UniProtAcc

Q5PSV4

Main function of 5'-partner protein: FUNCTION: Involved in the histone deacetylase (HDAC1)-dependent transcriptional repression activity. When overexpressed in lung cancer cell line that lacks p53/TP53 expression, inhibits cell growth. {ECO:0000269|PubMed:15451426}.

Q8IXF0

Main function of 5'-partner protein: FUNCTION: May play a broad role in neurogenesis. May control regulatory pathways relevant to schizophrenia and to psychotic illness (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000216807, ENST00000543183, 
ENST00000550662, ENST00000341321, 
ENST00000346562, ENST00000356141, 
ENST00000357798, ENST00000547068, 
ENST00000548645, ENST00000551008, 
ENST00000551492, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 4 X 4=8014 X 16 X 7=1568
# samples 516
** MAII scorelog2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1568*10)=-3.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: BRMS1L [Title/Abstract] AND NPAS3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BRMS1L [Title/Abstract] AND NPAS3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BRMS1L(36304129)-NPAS3(34029327), # samples:1
BRMS1L(36302311)-NPAS3(34029327), # samples:1
Anticipated loss of major functional domain due to fusion event.BRMS1L-NPAS3 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.
BRMS1L-NPAS3 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.
BRMS1L-NPAS3 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.
BRMS1L-NPAS3 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.
BRMS1L-NPAS3 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
BRMS1L-NPAS3 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
BRMS1L-NPAS3 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
BRMS1L-NPAS3 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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


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/chr14:36304129/chr14:34029327)
- 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 BRMS1L (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 NPAS3 (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)
ENST00000216807BRMS1Lchr1436304129+ENST00000551492NPAS3chr1434029327+29746401602973938
ENST00000216807BRMS1Lchr1436304129+ENST00000346562NPAS3chr1434029327+60416401602973937
ENST00000216807BRMS1Lchr1436304129+ENST00000341321NPAS3chr1434029327+946640160945262
ENST00000216807BRMS1Lchr1436304129+ENST00000548645NPAS3chr1434029327+31436401602973937
ENST00000216807BRMS1Lchr1436304129+ENST00000356141NPAS3chr1434029327+29746401602973938
ENST00000216807BRMS1Lchr1436304129+ENST00000357798NPAS3chr1434029327+29746401602973938
ENST00000216807BRMS1Lchr1436304129+ENST00000547068NPAS3chr1434029327+1345640160945261
ENST00000216807BRMS1Lchr1436304129+ENST00000551008NPAS3chr1434029327+1345640160945261
ENST00000543183BRMS1Lchr1436304129+ENST00000551492NPAS3chr1434029327+29646303332963876
ENST00000543183BRMS1Lchr1436304129+ENST00000346562NPAS3chr1434029327+60316303332963876
ENST00000543183BRMS1Lchr1436304129+ENST00000341321NPAS3chr1434029327+936630333935200
ENST00000543183BRMS1Lchr1436304129+ENST00000548645NPAS3chr1434029327+31336303332963876
ENST00000543183BRMS1Lchr1436304129+ENST00000356141NPAS3chr1434029327+29646303332963876
ENST00000543183BRMS1Lchr1436304129+ENST00000357798NPAS3chr1434029327+29646303332963876
ENST00000543183BRMS1Lchr1436304129+ENST00000547068NPAS3chr1434029327+1335630333935200
ENST00000543183BRMS1Lchr1436304129+ENST00000551008NPAS3chr1434029327+1335630333935200

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
ENST00000216807ENST00000551492BRMS1Lchr1436304129+NPAS3chr1434029327+0.0030154610.99698454
ENST00000216807ENST00000346562BRMS1Lchr1436304129+NPAS3chr1434029327+0.0002053310.99979466
ENST00000216807ENST00000341321BRMS1Lchr1436304129+NPAS3chr1434029327+0.0033956830.9966043
ENST00000216807ENST00000548645BRMS1Lchr1436304129+NPAS3chr1434029327+0.0031057220.99689424
ENST00000216807ENST00000356141BRMS1Lchr1436304129+NPAS3chr1434029327+0.0030154610.99698454
ENST00000216807ENST00000357798BRMS1Lchr1436304129+NPAS3chr1434029327+0.0030154610.99698454
ENST00000216807ENST00000547068BRMS1Lchr1436304129+NPAS3chr1434029327+0.0025597240.9974402
ENST00000216807ENST00000551008BRMS1Lchr1436304129+NPAS3chr1434029327+0.0025597240.9974402
ENST00000543183ENST00000551492BRMS1Lchr1436304129+NPAS3chr1434029327+0.002645520.9973545
ENST00000543183ENST00000346562BRMS1Lchr1436304129+NPAS3chr1434029327+0.0001377950.9998622
ENST00000543183ENST00000341321BRMS1Lchr1436304129+NPAS3chr1434029327+0.0029999140.99700004
ENST00000543183ENST00000548645BRMS1Lchr1436304129+NPAS3chr1434029327+0.0027015130.99729854
ENST00000543183ENST00000356141BRMS1Lchr1436304129+NPAS3chr1434029327+0.002645520.9973545
ENST00000543183ENST00000357798BRMS1Lchr1436304129+NPAS3chr1434029327+0.002645520.9973545
ENST00000543183ENST00000547068BRMS1Lchr1436304129+NPAS3chr1434029327+0.0019521930.9980478
ENST00000543183ENST00000551008BRMS1Lchr1436304129+NPAS3chr1434029327+0.0019521930.9980478

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 BRMS1L-NPAS3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BRMS1Lchr1436304129NPAS3chr143402932763099YECEIQASRQHCESLDGFVFALNQEG
BRMS1Lchr1436304129NPAS3chr1434029327640160YECEIQASRQHCESLDGFVFALNQEG

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Potential FusionNeoAntigen Information of BRMS1L-NPAS3 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.
BRMS1L-NPAS3_36304129_34029327.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)
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B18:01CESLDGFVF0.99240.97931120
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B38:02QHCESLDGF0.87740.7979918
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B38:01QHCESLDGF0.87560.7936918
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B13:01RQHCESLDGF0.81990.6457818
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B38:01QHCESLDGFVF0.99820.9212920
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B38:02QHCESLDGFVF0.9980.9145920
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B39:05QHCESLDGF0.87490.6724918
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-A68:02ESLDGFVFA0.99470.71081221
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B18:08CESLDGFVF0.99270.81861120
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B18:05CESLDGFVF0.99240.97931120
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-A69:01ESLDGFVFA0.98410.79561221
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-C03:05ASRQHCESL0.9680.8615615
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B07:13ASRQHCESL0.95510.8922615
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B38:05QHCESLDGF0.87560.7936918
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B18:11CESLDGFVF0.81610.97221120
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B39:11QHCESLDGF0.45340.7317918
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B15:50RQHCESLDGF0.99950.5864818
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-A68:02ESLDGFVFAL0.99710.65811222
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-A69:01ESLDGFVFAL0.99250.77561222
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B18:11HCESLDGFVF0.77670.8941020
BRMS1L-NPAS3chr1436304129chr1434029327640HLA-B38:05QHCESLDGFVF0.99820.9212920

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Potential FusionNeoAntigen Information of BRMS1L-NPAS3 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 BRMS1L-NPAS3

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
617ASRQHCESLDGFVFBRMS1LNPAS3chr1436304129chr1434029327640

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BRMS1L-NPAS3

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-B14:023BVN617ASRQHCESLDGFVF-7.9962-8.1096
HLA-B14:023BVN617ASRQHCESLDGFVF-5.70842-6.74372
HLA-B52:013W39617ASRQHCESLDGFVF-6.83737-6.95077
HLA-B52:013W39617ASRQHCESLDGFVF-4.4836-5.5189
HLA-A11:014UQ2617ASRQHCESLDGFVF-10.0067-10.1201
HLA-A11:014UQ2617ASRQHCESLDGFVF-9.03915-10.0745
HLA-A24:025HGA617ASRQHCESLDGFVF-6.56204-6.67544
HLA-A24:025HGA617ASRQHCESLDGFVF-5.42271-6.45801
HLA-B44:053DX8617ASRQHCESLDGFVF-7.85648-8.89178
HLA-B44:053DX8617ASRQHCESLDGFVF-5.3978-5.5112
HLA-A02:016TDR617ASRQHCESLDGFVF-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of BRMS1L-NPAS3

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
BRMS1L-NPAS3chr1436304129chr14340293271020HCESLDGFVFCATTGTGAGTCCCTGGATGGCTTTGTATTT
BRMS1L-NPAS3chr1436304129chr14340293271120CESLDGFVFTGTGAGTCCCTGGATGGCTTTGTATTT
BRMS1L-NPAS3chr1436304129chr14340293271221ESLDGFVFAGAGTCCCTGGATGGCTTTGTATTTGCA
BRMS1L-NPAS3chr1436304129chr14340293271222ESLDGFVFALGAGTCCCTGGATGGCTTTGTATTTGCACTA
BRMS1L-NPAS3chr1436304129chr1434029327615ASRQHCESLGCTTCTCGCCAGCATTGTGAGTCCCTG
BRMS1L-NPAS3chr1436304129chr1434029327818RQHCESLDGFCGCCAGCATTGTGAGTCCCTGGATGGCTTT
BRMS1L-NPAS3chr1436304129chr1434029327918QHCESLDGFCAGCATTGTGAGTCCCTGGATGGCTTT
BRMS1L-NPAS3chr1436304129chr1434029327920QHCESLDGFVFCAGCATTGTGAGTCCCTGGATGGCTTTGTATTT

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 BRMS1L-NPAS3

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
SARCBRMS1L-NPAS3chr1436304129ENST00000216807chr1434029327ENST00000341321TCGA-DX-A8BT-01A

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Potential target of CAR-T therapy development for BRMS1L-NPAS3

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 BRMS1L-NPAS3

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 BRMS1L-NPAS3

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