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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:HNRNPUL1-BRSK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HNRNPUL1-BRSK1
FusionPDB ID: 37305
FusionGDB2.0 ID: 37305
HgeneTgene
Gene symbol

HNRNPUL1

BRSK1

Gene ID

11100

84446

Gene nameheterogeneous nuclear ribonucleoprotein U like 1BR serine/threonine kinase 1
SynonymsE1B-AP5|E1BAP5|HNRPUL1hSAD1
Cytomap

19q13.2

19q13.42

Type of geneprotein-codingprotein-coding
Descriptionheterogeneous nuclear ribonucleoprotein U-like protein 1E1B 55kDa associated protein 5E1B-55 kDa-associated protein 5adenovirus early region 1B-associated protein 5serine/threonine-protein kinase BRSK1BR serine/threonine-protein kinase 1SAD1 homologSAD1 kinaseSadB kinase short isoformbrain-selective kinase 1brain-specific serine/threonine-protein kinase 1protein kinase SAD1Aserine/threonine-protein kinase SA
Modification date2020032720200313
UniProtAcc

Q9BUJ2

Main function of 5'-partner protein: FUNCTION: Acts as a basic transcriptional regulator. Represses basic transcription driven by several virus and cellular promoters. When associated with BRD7, activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation. Plays also a role in mRNA processing and transport. Binds avidly to poly(G) and poly(C) RNA homopolymers in vitro. {ECO:0000269|PubMed:12489984, ECO:0000269|PubMed:9733834}.

Q8TDC3

Main function of 5'-partner protein: FUNCTION: Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15150265, ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311}.
Ensembl transtripts involved in fusion geneENST idsENST00000263367, ENST00000352456, 
ENST00000392006, ENST00000593587, 
ENST00000595018, ENST00000602130, 
ENST00000378215, ENST00000594207, 
ENST00000326848, ENST00000588584, 
ENST00000309383, ENST00000585418, 
ENST00000590333, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 14 X 12=30245 X 5 X 4=100
# samples 205
** MAII scorelog2(20/3024*10)=-3.91838623444635
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/100*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HNRNPUL1 [Title/Abstract] AND BRSK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HNRNPUL1 [Title/Abstract] AND BRSK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HNRNPUL1(41787180)-BRSK1(55795889), # samples:1
Anticipated loss of major functional domain due to fusion event.HNRNPUL1-BRSK1 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.
HNRNPUL1-BRSK1 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.
HNRNPUL1-BRSK1 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.
HNRNPUL1-BRSK1 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.
HNRNPUL1-BRSK1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
HNRNPUL1-BRSK1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
HNRNPUL1-BRSK1 seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF.
HNRNPUL1-BRSK1 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
TgeneBRSK1

GO:0000086

G2/M transition of mitotic cell cycle

15150265

TgeneBRSK1

GO:0006468

protein phosphorylation

15150265

TgeneBRSK1

GO:0006974

cellular response to DNA damage stimulus

15150265

TgeneBRSK1

GO:0007095

mitotic G2 DNA damage checkpoint

15150265

TgeneBRSK1

GO:0009411

response to UV

15150265

TgeneBRSK1

GO:0010212

response to ionizing radiation

15150265

TgeneBRSK1

GO:0018105

peptidyl-serine phosphorylation

15150265



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/chr19:41787180/chr19:55795889)
- 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 HNRNPUL1 (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 BRSK1 (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)
ENST00000352456HNRNPUL1chr1941787180+ENST00000590333BRSK1chr1955795889+35157911130491012
ENST00000595018HNRNPUL1chr1941787180+ENST00000590333BRSK1chr1955795889+3492768453026993
ENST00000392006HNRNPUL1chr1941787180+ENST00000590333BRSK1chr1955795889+389611724434301128
ENST00000602130HNRNPUL1chr1941787180+ENST00000590333BRSK1chr1955795889+377610525333101085
ENST00000593587HNRNPUL1chr1941787180+ENST00000590333BRSK1chr1955795889+3517793943051985
ENST00000263367HNRNPUL1chr1941787180+ENST00000590333BRSK1chr1955795889+365092616131841007

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
ENST00000352456ENST00000590333HNRNPUL1chr1941787180+BRSK1chr1955795889+0.0021457380.9978543
ENST00000595018ENST00000590333HNRNPUL1chr1941787180+BRSK1chr1955795889+0.0022564640.9977436
ENST00000392006ENST00000590333HNRNPUL1chr1941787180+BRSK1chr1955795889+0.0033780140.99662197
ENST00000602130ENST00000590333HNRNPUL1chr1941787180+BRSK1chr1955795889+0.0032458430.9967541
ENST00000593587ENST00000590333HNRNPUL1chr1941787180+BRSK1chr1955795889+0.0025108660.9974891
ENST00000263367ENST00000590333HNRNPUL1chr1941787180+BRSK1chr1955795889+0.002376960.997623

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 HNRNPUL1-BRSK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HNRNPUL1chr1941787180BRSK1chr19557958891052333DKFAENDVIGCFAHAQYVGPYRLEKT
HNRNPUL1chr1941787180BRSK1chr19557958891172376DKFAENDVIGCFAHAQYVGPYRLEKT
HNRNPUL1chr1941787180BRSK1chr1955795889768241DKFAENDVIGCFAHAQYVGPYRLEKT
HNRNPUL1chr1941787180BRSK1chr1955795889791260DKFAENDVIGCFAHAQYVGPYRLEKT
HNRNPUL1chr1941787180BRSK1chr1955795889793233DKFAENDVIGCFAHAQYVGPYRLEKT
HNRNPUL1chr1941787180BRSK1chr1955795889926255DKFAENDVIGCFAHAQYVGPYRLEKT

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Potential FusionNeoAntigen Information of HNRNPUL1-BRSK1 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.
HNRNPUL1-BRSK1_41787180_55795889.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)
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A26:03DVIGCFAHA0.99270.8787615
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B15:18AHAQYVGPY0.4930.54491221
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B15:03AHAQYVGPY0.47250.611221
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A26:02DVIGCFAHAQY0.99970.7464617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A26:14DVIGCFAHAQY0.99940.7637617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A26:15DVIGCFAHAQY0.99940.7637617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B38:01AHAQYVGPYRL0.99880.97761223
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B38:02AHAQYVGPYRL0.99870.97961223
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A66:01DVIGCFAHAQY0.99720.7735617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A26:03DVIGCFAHAQY0.99410.7803617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A26:08DVIGCFAHAQY0.98210.5593617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A34:05DVIGCFAHAQY0.94510.6235617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A34:01DVIGCFAHAQY0.94510.6235617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B48:01AHAQYVGPYRL0.87460.69021223
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A66:03DVIGCFAHAQY0.6790.6166617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B15:21AHAQYVGPY0.70180.75671221
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A26:01DVIGCFAHAQY0.99940.7637617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B39:05AHAQYVGPYRL0.99840.93561223
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A68:02DVIGCFAHA0.99470.7558615
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A69:01DVIGCFAHA0.98690.8011615
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B15:54AHAQYVGPY0.04260.63571221
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-A25:01DVIGCFAHAQY0.99930.9729617
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B38:05AHAQYVGPYRL0.99880.97761223
HNRNPUL1-BRSK1chr1941787180chr1955795889926HLA-B39:11AHAQYVGPYRL0.97770.92591223

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Potential FusionNeoAntigen Information of HNRNPUL1-BRSK1 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 HNRNPUL1-BRSK1

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
1459DVIGCFAHAQYVGPHNRNPUL1BRSK1chr1941787180chr1955795889926

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HNRNPUL1-BRSK1

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-B14:023BVN1459DVIGCFAHAQYVGP-7.9962-8.1096
HLA-B14:023BVN1459DVIGCFAHAQYVGP-5.70842-6.74372
HLA-B52:013W391459DVIGCFAHAQYVGP-6.83737-6.95077
HLA-B52:013W391459DVIGCFAHAQYVGP-4.4836-5.5189
HLA-A11:014UQ21459DVIGCFAHAQYVGP-10.0067-10.1201
HLA-A11:014UQ21459DVIGCFAHAQYVGP-9.03915-10.0745
HLA-A24:025HGA1459DVIGCFAHAQYVGP-6.56204-6.67544
HLA-A24:025HGA1459DVIGCFAHAQYVGP-5.42271-6.45801
HLA-B44:053DX81459DVIGCFAHAQYVGP-7.85648-8.89178
HLA-B44:053DX81459DVIGCFAHAQYVGP-5.3978-5.5112
HLA-A02:016TDR1459DVIGCFAHAQYVGP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of HNRNPUL1-BRSK1

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
HNRNPUL1-BRSK1chr1941787180chr19557958891221AHAQYVGPYGCGCACGCCCAATATGTGGGCCCCTAT
HNRNPUL1-BRSK1chr1941787180chr19557958891223AHAQYVGPYRLGCGCACGCCCAATATGTGGGCCCCTATCGGCTG
HNRNPUL1-BRSK1chr1941787180chr1955795889615DVIGCFAHAGATGTGATTGGCTGCTTTGCGCACGCC
HNRNPUL1-BRSK1chr1941787180chr1955795889617DVIGCFAHAQYGATGTGATTGGCTGCTTTGCGCACGCCCAATAT

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 HNRNPUL1-BRSK1

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
CESCHNRNPUL1-BRSK1chr1941787180ENST00000263367chr1955795889ENST00000590333TCGA-C5-A907-01A

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Potential target of CAR-T therapy development for HNRNPUL1-BRSK1

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 HNRNPUL1-BRSK1

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 HNRNPUL1-BRSK1

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