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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-CYP2S1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HNRNPUL1-CYP2S1
FusionPDB ID: 37309
FusionGDB2.0 ID: 37309
HgeneTgene
Gene symbol

HNRNPUL1

CYP2S1

Gene ID

11100

29785

Gene nameheterogeneous nuclear ribonucleoprotein U like 1cytochrome P450 family 2 subfamily S member 1
SynonymsE1B-AP5|E1BAP5|HNRPUL1CYPIIS1
Cytomap

19q13.2

19q13.2

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 5cytochrome P450 2S1cytochrome P450, family 2, subfamily S, polypeptide 1cytochrome P540, subfamily IIS, polypeptide 1hydroperoxy icosatetraenoate dehydratasethromboxane-A synthase
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}.

Q96SQ9

Main function of 5'-partner protein: FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of retinoids and eicosanoids (PubMed:12711469, PubMed:21068195). In epidermis, may contribute to the oxidative metabolism of all-trans-retinoic acid. For this activity, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12711469). Additionally, displays peroxidase and isomerase activities toward various oxygenated eicosanoids such as prostaglandin H2 (PGH2) and hydroperoxyeicosatetraenoates (HPETEs) (PubMed:21068195). Independently of cytochrome P450 reductase, NADPH, and O2, catalyzes the breakdown of PGH2 to hydroxyheptadecatrienoic acid (HHT) and malondialdehyde (MDA), which is known to act as a mediator of DNA damage (PubMed:21068195). {ECO:0000269|PubMed:12711469, ECO:0000269|PubMed:21068195}.
Ensembl transtripts involved in fusion geneENST idsENST00000378215, ENST00000392006, 
ENST00000602130, ENST00000263367, 
ENST00000352456, ENST00000593587, 
ENST00000595018, ENST00000594207, 
ENST00000542619, ENST00000310054, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 14 X 12=30246 X 6 X 5=180
# samples 207
** MAII scorelog2(20/3024*10)=-3.91838623444635
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/180*10)=-1.36257007938471
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HNRNPUL1 [Title/Abstract] AND CYP2S1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HNRNPUL1 [Title/Abstract] AND CYP2S1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HNRNPUL1(41770597)-CYP2S1(41700449), # samples:1
HNRNPUL1(41770703)-CYP2S1(41700449), # samples:1
HNRNPUL1(41807609)-CYP2S1(41703684), # samples:1
Anticipated loss of major functional domain due to fusion event.HNRNPUL1-CYP2S1 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-CYP2S1 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-CYP2S1 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-CYP2S1 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-CYP2S1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
HNRNPUL1-CYP2S1 seems lost the major protein functional domain in Tgene 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
TgeneCYP2S1

GO:0006690

icosanoid metabolic process

21068195

TgeneCYP2S1

GO:0006693

prostaglandin metabolic process

21068195

TgeneCYP2S1

GO:0042573

retinoic acid metabolic process

12711469



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/chr19:41770597/chr19:41700449)
- 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 CYP2S1 (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)
ENST00000352456HNRNPUL1chr1941807609+ENST00000310054CYP2S1chr1941703684+37021479112650879
ENST00000595018HNRNPUL1chr1941807609+ENST00000310054CYP2S1chr1941703684+36791456452627860
ENST00000392006HNRNPUL1chr1941807609+ENST00000310054CYP2S1chr1941703684+40831860443031995
ENST00000378215HNRNPUL1chr1941807609+ENST00000310054CYP2S1chr1941703684+3700147732648881
ENST00000602130HNRNPUL1chr1941807609+ENST00000310054CYP2S1chr1941703684+39631740532911952
ENST00000593587HNRNPUL1chr1941807609+ENST00000310054CYP2S1chr1941703684+37041481942652852
ENST00000263367HNRNPUL1chr1941807609+ENST00000310054CYP2S1chr1941703684+383716141612785874

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
ENST00000352456ENST00000310054HNRNPUL1chr1941807609+CYP2S1chr1941703684+0.0017789990.998221
ENST00000595018ENST00000310054HNRNPUL1chr1941807609+CYP2S1chr1941703684+0.0018642250.9981358
ENST00000392006ENST00000310054HNRNPUL1chr1941807609+CYP2S1chr1941703684+0.0039191930.9960808
ENST00000378215ENST00000310054HNRNPUL1chr1941807609+CYP2S1chr1941703684+0.004805310.9951946
ENST00000602130ENST00000310054HNRNPUL1chr1941807609+CYP2S1chr1941703684+0.004098830.99590117
ENST00000593587ENST00000310054HNRNPUL1chr1941807609+CYP2S1chr1941703684+0.002002620.99799734
ENST00000263367ENST00000310054HNRNPUL1chr1941807609+CYP2S1chr1941703684+0.0015192260.99848074

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-CYP2S1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HNRNPUL1chr1941807609CYP2S1chr19417036841456470GKDVPDHAVLEMKGVFFSNGERWRQL
HNRNPUL1chr1941807609CYP2S1chr19417036841477491GKDVPDHAVLEMKGVFFSNGERWRQL
HNRNPUL1chr1941807609CYP2S1chr19417036841479489GKDVPDHAVLEMKGVFFSNGERWRQL
HNRNPUL1chr1941807609CYP2S1chr19417036841481462GKDVPDHAVLEMKGVFFSNGERWRQL
HNRNPUL1chr1941807609CYP2S1chr19417036841614484GKDVPDHAVLEMKGVFFSNGERWRQL
HNRNPUL1chr1941807609CYP2S1chr19417036841740562GKDVPDHAVLEMKGVFFSNGERWRQL
HNRNPUL1chr1941807609CYP2S1chr19417036841860605GKDVPDHAVLEMKGVFFSNGERWRQL

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Potential FusionNeoAntigen Information of HNRNPUL1-CYP2S1 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-CYP2S1_41807609_41703684.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-CYP2S1chr1941807609chr19417036841614HLA-B18:01LEMKGVFF0.9980.8739917
HNRNPUL1-CYP2S1chr1941807609chr19417036841614HLA-B58:02KGVFFSNGERW0.99980.75661223
HNRNPUL1-CYP2S1chr1941807609chr19417036841614HLA-B58:01KGVFFSNGERW0.99960.73221223
HNRNPUL1-CYP2S1chr1941807609chr19417036841614HLA-B18:08LEMKGVFF0.99820.7215917
HNRNPUL1-CYP2S1chr1941807609chr19417036841614HLA-B18:06LEMKGVFF0.99810.8866917
HNRNPUL1-CYP2S1chr1941807609chr19417036841614HLA-B18:05LEMKGVFF0.9980.8739917
HNRNPUL1-CYP2S1chr1941807609chr19417036841614HLA-B18:03LEMKGVFF0.99710.8679917
HNRNPUL1-CYP2S1chr1941807609chr19417036841614HLA-B18:11LEMKGVFF0.97730.9053917
HNRNPUL1-CYP2S1chr1941807609chr19417036841614HLA-C04:03VLEMKGVFF0.99450.8343817

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Potential FusionNeoAntigen Information of HNRNPUL1-CYP2S1 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-CYP2S1

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
3281HAVLEMKGVFFSNGHNRNPUL1CYP2S1chr1941807609chr19417036841614

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HNRNPUL1-CYP2S1

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-B14:023BVN3281HAVLEMKGVFFSNG-7.9962-8.1096
HLA-B14:023BVN3281HAVLEMKGVFFSNG-5.70842-6.74372
HLA-B52:013W393281HAVLEMKGVFFSNG-6.83737-6.95077
HLA-B52:013W393281HAVLEMKGVFFSNG-4.4836-5.5189
HLA-A11:014UQ23281HAVLEMKGVFFSNG-10.0067-10.1201
HLA-A11:014UQ23281HAVLEMKGVFFSNG-9.03915-10.0745
HLA-A24:025HGA3281HAVLEMKGVFFSNG-6.56204-6.67544
HLA-A24:025HGA3281HAVLEMKGVFFSNG-5.42271-6.45801
HLA-B44:053DX83281HAVLEMKGVFFSNG-7.85648-8.89178
HLA-B44:053DX83281HAVLEMKGVFFSNG-5.3978-5.5112
HLA-A02:016TDR3281HAVLEMKGVFFSNG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of HNRNPUL1-CYP2S1

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-CYP2S1chr1941807609chr19417036841223KGVFFSNGERWAAGGGGTTTTCTTCTCCAACGGGGAGCGGTGGA
HNRNPUL1-CYP2S1chr1941807609chr1941703684817VLEMKGVFFTCTTAGAAATGAAAGGGGTTTTCTTCT
HNRNPUL1-CYP2S1chr1941807609chr1941703684917LEMKGVFFTAGAAATGAAAGGGGTTTTCTTCT

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-CYP2S1

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
OVHNRNPUL1-CYP2S1chr1941807609ENST00000263367chr1941703684ENST00000310054TCGA-30-1718-01A

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Potential target of CAR-T therapy development for HNRNPUL1-CYP2S1

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-CYP2S1

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-CYP2S1

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