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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:HNF1B-FHOD3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HNF1B-FHOD3
FusionPDB ID: 37006
FusionGDB2.0 ID: 37006
HgeneTgene
Gene symbol

HNF1B

FHOD3

Gene ID

6928

91010

Gene nameHNF1 homeobox Bformin like 3
SynonymsFJHN|HNF-1-beta|HNF-1B|HNF1beta|HNF2|HPC11|LF-B3|LFB3|MODY5|TCF-2|TCF2|VHNF1FHOD3|FRL2|WBP-3|WBP3
Cytomap

17q12

12q13.12

Type of geneprotein-codingprotein-coding
Descriptionhepatocyte nuclear factor 1-betaHNF1 beta Ahomeoprotein LFB3transcription factor 2, hepaticformin-like protein 3WW domain binding protein 3formin homology 2 domain-containing protein 3
Modification date2020031320200322
UniProtAcc

P35680

Main function of 5'-partner protein: FUNCTION: Transcription factor, probably binds to the inverted palindrome 5'-GTTAATNATTAAC-3'.

Q2V2M9

Main function of 5'-partner protein: FUNCTION: Actin-organizing protein that may cause stress fiber formation together with cell elongation (By similarity). Isoform 4 may play a role in actin filament polymerization in cardiomyocytes. {ECO:0000250, ECO:0000269|PubMed:21149568}.
Ensembl transtripts involved in fusion geneENST idsENST00000225893, ENST00000561193, 
ENST00000427275, ENST00000560016, 
ENST00000592128, ENST00000587493, 
ENST00000257209, ENST00000359247, 
ENST00000445677, ENST00000590592, 
ENST00000591635, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 10 X 8=80010 X 11 X 4=440
# samples 1011
** MAII scorelog2(10/800*10)=-3
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/440*10)=-2
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HNF1B [Title/Abstract] AND FHOD3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HNF1B [Title/Abstract] AND FHOD3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HNF1B(36059082)-FHOD3(34310609), # samples:1
Anticipated loss of major functional domain due to fusion event.HNF1B-FHOD3 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.
HNF1B-FHOD3 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.
HNF1B-FHOD3 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.
HNF1B-FHOD3 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
HgeneHNF1B

GO:0001822

kidney development

21281489

HgeneHNF1B

GO:0045893

positive regulation of transcription, DNA-templated

16297991|21281489

HgeneHNF1B

GO:0060261

positive regulation of transcription initiation from RNA polymerase II promoter

15355349



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/chr17:36059082/chr18:34310609)
- 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 HNF1B (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 FHOD3 (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)
ENST00000225893HNF1Bchr1736059082-ENST00000257209FHOD3chr1834310609+3968201536234421026
ENST00000225893HNF1Bchr1736059082-ENST00000445677FHOD3chr1834310609+3968201536234421026
ENST00000225893HNF1Bchr1736059082-ENST00000590592FHOD3chr1834310609+3467201536234661035
ENST00000225893HNF1Bchr1736059082-ENST00000359247FHOD3chr1834310609+3692201536234421026
ENST00000225893HNF1Bchr1736059082-ENST00000591635FHOD3chr1834310609+3968201536234421026
ENST00000561193HNF1Bchr1736059082-ENST00000257209FHOD3chr1834310609+3703175017531771000
ENST00000561193HNF1Bchr1736059082-ENST00000445677FHOD3chr1834310609+3703175017531771000
ENST00000561193HNF1Bchr1736059082-ENST00000590592FHOD3chr1834310609+3202175017532011009
ENST00000561193HNF1Bchr1736059082-ENST00000359247FHOD3chr1834310609+3427175017531771000
ENST00000561193HNF1Bchr1736059082-ENST00000591635FHOD3chr1834310609+3703175017531771000

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
ENST00000225893ENST00000257209HNF1Bchr1736059082-FHOD3chr1834310609+0.0015246040.9984754
ENST00000225893ENST00000445677HNF1Bchr1736059082-FHOD3chr1834310609+0.0015246040.9984754
ENST00000225893ENST00000590592HNF1Bchr1736059082-FHOD3chr1834310609+0.0039620630.99603796
ENST00000225893ENST00000359247HNF1Bchr1736059082-FHOD3chr1834310609+0.0030752790.9969247
ENST00000225893ENST00000591635HNF1Bchr1736059082-FHOD3chr1834310609+0.0015246040.9984754
ENST00000561193ENST00000257209HNF1Bchr1736059082-FHOD3chr1834310609+0.0009107890.99908924
ENST00000561193ENST00000445677HNF1Bchr1736059082-FHOD3chr1834310609+0.0009107890.99908924
ENST00000561193ENST00000590592HNF1Bchr1736059082-FHOD3chr1834310609+0.0030895710.9969104
ENST00000561193ENST00000359247HNF1Bchr1736059082-FHOD3chr1834310609+0.0021826190.9978174
ENST00000561193ENST00000591635HNF1Bchr1736059082-FHOD3chr1834310609+0.0009107890.99908924

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 HNF1B-FHOD3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HNF1Bchr1736059082FHOD3chr18343106091750525SISTLTNMSSSKQKTAADGKRQEIIV
HNF1Bchr1736059082FHOD3chr18343106092015551SISTLTNMSSSKQKTAADGKRQEIIV

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Potential FusionNeoAntigen Information of HNF1B-FHOD3 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.
HNF1B-FHOD3_36059082_34310609.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)
HNF1B-FHOD3chr1736059082chr18343106092015HLA-A30:01KQKTAADGK0.97580.54051120

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Potential FusionNeoAntigen Information of HNF1B-FHOD3 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.
HNF1B-FHOD3_36059082_34310609.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)
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0403ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0413ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0415ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0427ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0436ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0437ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0439ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0440ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0440SISTLTNMSSSKQKT015
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0441ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0442ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0442SISTLTNMSSSKQKT015
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0444ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0446ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0449ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0450ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0452ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0453ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0453SISTLTNMSSSKQKT015
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0455ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0456ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0456SISTLTNMSSSKQKT015
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0458ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0459ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0460ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0468ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0468SISTLTNMSSSKQKT015
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0470ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0471ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0473ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0479ISTLTNMSSSKQKTA116
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0479SISTLTNMSSSKQKT015
HNF1B-FHOD3chr1736059082chr18343106092015DRB1-0485ISTLTNMSSSKQKTA116

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Fusion breakpoint peptide structures of HNF1B-FHOD3

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
6276NMSSSKQKTAADGKHNF1BFHOD3chr1736059082chr18343106092015

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HNF1B-FHOD3

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-B14:023BVN6276NMSSSKQKTAADGK-8.62545-8.73885
HLA-B14:023BVN6276NMSSSKQKTAADGK-3.26321-4.29851
HLA-B52:013W396276NMSSSKQKTAADGK-6.23413-6.34753
HLA-B52:013W396276NMSSSKQKTAADGK-4.55402-5.58932
HLA-A24:025HGA6276NMSSSKQKTAADGK-8.62578-8.73918
HLA-A24:025HGA6276NMSSSKQKTAADGK-6.438-7.4733
HLA-B44:053DX86276NMSSSKQKTAADGK-5.68484-5.79824
HLA-B44:053DX86276NMSSSKQKTAADGK-3.64855-4.68385
HLA-A02:016TDR6276NMSSSKQKTAADGK-5.14764-6.18294

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Vaccine Design for the FusionNeoAntigens of HNF1B-FHOD3

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
HNF1B-FHOD3chr1736059082chr18343106091120KQKTAADGKAAACAGAAAACTGCTGCAGATGGAAAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
HNF1B-FHOD3chr1736059082chr1834310609015SISTLTNMSSSKQKTAGCATCAGTACACTCACCAACATGTCTTCAAGTAAACAGAAAACT
HNF1B-FHOD3chr1736059082chr1834310609116ISTLTNMSSSKQKTAATCAGTACACTCACCAACATGTCTTCAAGTAAACAGAAAACTGCT

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Information of the samples that have these potential fusion neoantigens of HNF1B-FHOD3

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
STADHNF1B-FHOD3chr1736059082ENST00000225893chr1834310609ENST00000257209TCGA-HU-8238-01A

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Potential target of CAR-T therapy development for HNF1B-FHOD3

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 HNF1B-FHOD3

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 HNF1B-FHOD3

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