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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:SLCO2B1-HNF4A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SLCO2B1-HNF4A
FusionPDB ID: 83599
FusionGDB2.0 ID: 83599
HgeneTgene
Gene symbol

SLCO2B1

HNF4A

Gene ID

11309

6927

Gene namesolute carrier organic anion transporter family member 2B1HNF1 homeobox A
SynonymsOATP-B|OATP2B1|OATPB|SLC21A9HNF-1A|HNF1|HNF4A|IDDM20|LFB1|MODY3|TCF-1|TCF1
Cytomap

11q13.4

12q24.31

Type of geneprotein-codingprotein-coding
Descriptionsolute carrier organic anion transporter family member 2B1OATP-RP2organic anion transporter Borganic anion transporter polypeptide-related protein 2solute carrier family 21 (organic anion transporter), member 9hepatocyte nuclear factor 1-alphaHNF-1-alphaalbumin proximal factorhepatic nuclear factor 1interferon production regulator factorliver-specific transcription factor LF-B1transcription factor 1, hepatictruncated hepatocyte nuclear factor 1 alpha
Modification date2020031520200313
UniProtAcc.

P41235

Main function of 5'-partner protein: FUNCTION: Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698). {ECO:0000250|UniProtKB:P49698, ECO:0000269|PubMed:30530698, ECO:0000269|PubMed:30597922}.
Ensembl transtripts involved in fusion geneENST idsENST00000341411, ENST00000428359, 
ENST00000454962, ENST00000532236, 
ENST00000289575, ENST00000525650, 
ENST00000531756, ENST00000526660, 
ENST00000316099, ENST00000316673, 
ENST00000415691, ENST00000443598, 
ENST00000457232, ENST00000609795, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 6 X 4=966 X 6 X 5=180
# samples 57
** MAII scorelog2(5/96*10)=-0.941106310946431
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: SLCO2B1 [Title/Abstract] AND HNF4A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SLCO2B1 [Title/Abstract] AND HNF4A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SLCO2B1(74870917)-HNF4A(43034698), # samples:2
SLCO2B1(74870917)-HNF4A(43031194), # samples:2
Anticipated loss of major functional domain due to fusion event.SLCO2B1-HNF4A 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.
SLCO2B1-HNF4A 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.
SLCO2B1-HNF4A 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.
SLCO2B1-HNF4A 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
HgeneSLCO2B1

GO:0015711

organic anion transport

12724351|22021325

HgeneSLCO2B1

GO:0055085

transmembrane transport

12724351|29871943

TgeneHNF4A

GO:0001779

natural killer cell differentiation

11301190

TgeneHNF4A

GO:0006357

regulation of transcription by RNA polymerase II

10330009

TgeneHNF4A

GO:0045893

positive regulation of transcription, DNA-templated

1989880|11980910|12453420



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/chr11:74870917/chr20:43034698)
- 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 SLCO2B1 (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 HNF4A (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)
ENST00000289575SLCO2B1chr1174862442-ENST00000316673HNF4Achr2043034698+17274113951720441
ENST00000289575SLCO2B1chr1174862442-ENST00000609795HNF4Achr2043034698+15504113951549385
ENST00000289575SLCO2B1chr1174862442-ENST00000457232HNF4Achr2043034698+16974113951690431
ENST00000289575SLCO2B1chr1174862442-ENST00000443598HNF4Achr2043034698+18104113951549384
ENST00000289575SLCO2B1chr1174862442-ENST00000316099HNF4Achr2043034698+49014113951720441
ENST00000289575SLCO2B1chr1174862442-ENST00000415691HNF4Achr2043034698+25264113951690431
ENST00000531756SLCO2B1chr1174862442-ENST00000316673HNF4Achr2043034698+16443283121637441
ENST00000531756SLCO2B1chr1174862442-ENST00000609795HNF4Achr2043034698+14673283121466384
ENST00000531756SLCO2B1chr1174862442-ENST00000457232HNF4Achr2043034698+16143283121607431
ENST00000531756SLCO2B1chr1174862442-ENST00000443598HNF4Achr2043034698+17273283121466384
ENST00000531756SLCO2B1chr1174862442-ENST00000316099HNF4Achr2043034698+48183283121637441
ENST00000531756SLCO2B1chr1174862442-ENST00000415691HNF4Achr2043034698+24433283121607431
ENST00000525650SLCO2B1chr1174862442-ENST00000316673HNF4Achr2043034698+15992832671592441
ENST00000525650SLCO2B1chr1174862442-ENST00000609795HNF4Achr2043034698+14222832671421384
ENST00000525650SLCO2B1chr1174862442-ENST00000457232HNF4Achr2043034698+15692832671562431
ENST00000525650SLCO2B1chr1174862442-ENST00000443598HNF4Achr2043034698+16822832671421384
ENST00000525650SLCO2B1chr1174862442-ENST00000316099HNF4Achr2043034698+47732832671592441
ENST00000525650SLCO2B1chr1174862442-ENST00000415691HNF4Achr2043034698+23982832671562431

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
ENST00000289575ENST00000316673SLCO2B1chr1174862442-HNF4Achr2043034698+0.0301549960.96984494
ENST00000289575ENST00000609795SLCO2B1chr1174862442-HNF4Achr2043034698+0.0301950890.96980494
ENST00000289575ENST00000457232SLCO2B1chr1174862442-HNF4Achr2043034698+0.0196527430.9803473
ENST00000289575ENST00000443598SLCO2B1chr1174862442-HNF4Achr2043034698+0.026503470.97349656
ENST00000289575ENST00000316099SLCO2B1chr1174862442-HNF4Achr2043034698+0.0113707910.9886292
ENST00000289575ENST00000415691SLCO2B1chr1174862442-HNF4Achr2043034698+0.0201944910.9798055
ENST00000531756ENST00000316673SLCO2B1chr1174862442-HNF4Achr2043034698+0.0260305160.97396946
ENST00000531756ENST00000609795SLCO2B1chr1174862442-HNF4Achr2043034698+0.0301270220.969873
ENST00000531756ENST00000457232SLCO2B1chr1174862442-HNF4Achr2043034698+0.0163827650.9836172
ENST00000531756ENST00000443598SLCO2B1chr1174862442-HNF4Achr2043034698+0.0251462330.97485375
ENST00000531756ENST00000316099SLCO2B1chr1174862442-HNF4Achr2043034698+0.011066910.9889331
ENST00000531756ENST00000415691SLCO2B1chr1174862442-HNF4Achr2043034698+0.0187513960.9812486
ENST00000525650ENST00000316673SLCO2B1chr1174862442-HNF4Achr2043034698+0.0216605230.97833943
ENST00000525650ENST00000609795SLCO2B1chr1174862442-HNF4Achr2043034698+0.0276165870.97238344
ENST00000525650ENST00000457232SLCO2B1chr1174862442-HNF4Achr2043034698+0.0137832130.9862168
ENST00000525650ENST00000443598SLCO2B1chr1174862442-HNF4Achr2043034698+0.0226026870.97739726
ENST00000525650ENST00000316099SLCO2B1chr1174862442-HNF4Achr2043034698+0.0108892180.98911077
ENST00000525650ENST00000415691SLCO2B1chr1174862442-HNF4Achr2043034698+0.0171860830.98281395

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 SLCO2B1-HNF4A

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

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Potential FusionNeoAntigen Information of SLCO2B1-HNF4A 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.

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)

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Potential FusionNeoAntigen Information of SLCO2B1-HNF4A 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 SLCO2B1-HNF4A

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SLCO2B1-HNF4A

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

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Vaccine Design for the FusionNeoAntigens of SLCO2B1-HNF4A

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

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 SLCO2B1-HNF4A

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

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Potential target of CAR-T therapy development for SLCO2B1-HNF4A

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 SLCO2B1-HNF4A

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 SLCO2B1-HNF4A

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