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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:HOOK3-GTF2E2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HOOK3-GTF2E2
FusionPDB ID: 37388
FusionGDB2.0 ID: 37388
HgeneTgene
Gene symbol

HOOK3

GTF2E2

Gene ID

84376

2961

Gene namehook microtubule tethering protein 3general transcription factor IIE subunit 2
SynonymsHK3FE|TF2E2|TFIIE-B|TTD6
Cytomap

8p11.21

8p12

Type of geneprotein-codingprotein-coding
Descriptionprotein Hook homolog 3h-hook3hHK3hook homolog 3transcription initiation factor IIE subunit betaTFIIE beta subunitTFIIE-betageneral transcription factor IIE, polypeptide 2, beta 34kDa
Modification date2020031320200313
UniProtAcc

Q86VS8

Main function of 5'-partner protein: FUNCTION: Probably serves as a target for the spiC protein from Salmonella typhimurium, which inactivates it, leading to a strong alteration in cellular trafficking (By similarity). Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). May regulate clearance of endocytosed receptors such as MSR1. Participates in defining the architecture and localization of the Golgi complex. Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (PubMed:25035494). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997). {ECO:0000250|UniProtKB:Q8BUK6, ECO:0000269|PubMed:11238449, ECO:0000269|PubMed:17237231, ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:25035494, ECO:0000269|PubMed:32073997}.; FUNCTION: (Microbial infection) May serve as a target for the spiC protein from Salmonella typhimurium, which inactivates it, leading to a strong alteration in cellular trafficking. {ECO:0000305}.

P29084

Main function of 5'-partner protein: FUNCTION: Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase. {ECO:0000269|PubMed:1956398, ECO:0000269|PubMed:1956404}.
Ensembl transtripts involved in fusion geneENST idsENST00000307602, ENST00000524839, 
ENST00000522833, ENST00000355904, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 13 X 9=187210 X 6 X 6=360
# samples 1911
** MAII scorelog2(19/1872*10)=-3.30050911125246
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/360*10)=-1.71049338280502
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HOOK3 [Title/Abstract] AND GTF2E2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HOOK3 [Title/Abstract] AND GTF2E2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HOOK3(42798588)-GTF2E2(30492640), # samples:3
Anticipated loss of major functional domain due to fusion event.HOOK3-GTF2E2 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.
HOOK3-GTF2E2 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.
HOOK3-GTF2E2 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.
HOOK3-GTF2E2 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
TgeneGTF2E2

GO:0006366

transcription by RNA polymerase II

27193682



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/chr8:42798588/chr8:30492640)
- 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 HOOK3 (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 GTF2E2 (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)
ENST00000307602HOOK3chr842798588+ENST00000355904GTF2E2chr830492640-19136001821309375

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
ENST00000307602ENST00000355904HOOK3chr842798588+GTF2E2chr830492640-0.0008281620.99917185

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 HOOK3-GTF2E2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HOOK3chr842798588GTF2E2chr830492640600139LILGCAVNCEQKQDHSNGSFNLKALS

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Potential FusionNeoAntigen Information of HOOK3-GTF2E2 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.
HOOK3-GTF2E2_42798588_30492640.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)
HOOK3-GTF2E2chr842798588chr830492640600HLA-B39:13KQDHSNGSF0.43530.64131120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B13:01KQDHSNGSF0.39520.69541120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B39:01QDHSNGSFNL0.70980.74831222
HOOK3-GTF2E2chr842798588chr830492640600HLA-B38:01QDHSNGSFNL0.59410.80181222
HOOK3-GTF2E2chr842798588chr830492640600HLA-B38:02QDHSNGSFNL0.57020.81911222
HOOK3-GTF2E2chr842798588chr830492640600HLA-C05:09KQDHSNGSF0.99770.80431120
HOOK3-GTF2E2chr842798588chr830492640600HLA-C04:07KQDHSNGSF0.99710.59531120
HOOK3-GTF2E2chr842798588chr830492640600HLA-C04:10KQDHSNGSF0.9970.50761120
HOOK3-GTF2E2chr842798588chr830492640600HLA-C08:15KQDHSNGSF0.99510.91551120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B15:05KQDHSNGSF0.52850.60961120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B39:08KQDHSNGSF0.45240.51861120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B39:05QDHSNGSFNL0.58770.72471222
HOOK3-GTF2E2chr842798588chr830492640600HLA-C04:03KQDHSNGSF0.99770.69521120
HOOK3-GTF2E2chr842798588chr830492640600HLA-C05:01KQDHSNGSF0.99770.80431120
HOOK3-GTF2E2chr842798588chr830492640600HLA-C04:01KQDHSNGSF0.99710.59531120
HOOK3-GTF2E2chr842798588chr830492640600HLA-C18:01KQDHSNGSF0.99660.70091120
HOOK3-GTF2E2chr842798588chr830492640600HLA-C08:02KQDHSNGSF0.99510.91551120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B15:50KQDHSNGSF0.98420.57521120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B15:53KQDHSNGSF0.84770.57691120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B15:39KQDHSNGSF0.80460.50311120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B15:54KQDHSNGSF0.78480.56161120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B15:30KQDHSNGSF0.52460.56561120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B39:02KQDHSNGSF0.52290.63541120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B15:20KQDHSNGSF0.51850.68451120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B48:02KQDHSNGSF0.49680.68251120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B35:28KQDHSNGSF0.48630.70141120
HOOK3-GTF2E2chr842798588chr830492640600HLA-B39:11QDHSNGSFNL0.78630.69481222
HOOK3-GTF2E2chr842798588chr830492640600HLA-B38:05QDHSNGSFNL0.59410.80181222
HOOK3-GTF2E2chr842798588chr830492640600HLA-B15:53EQKQDHSNGSF0.99910.5222920
HOOK3-GTF2E2chr842798588chr830492640600HLA-B15:12EQKQDHSNGSF0.99390.6321920

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Potential FusionNeoAntigen Information of HOOK3-GTF2E2 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 HOOK3-GTF2E2

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
10132VNCEQKQDHSNGSFHOOK3GTF2E2chr842798588chr830492640600

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HOOK3-GTF2E2

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-B14:023BVN10132VNCEQKQDHSNGSF-7.9962-8.1096
HLA-B14:023BVN10132VNCEQKQDHSNGSF-5.70842-6.74372
HLA-B52:013W3910132VNCEQKQDHSNGSF-6.83737-6.95077
HLA-B52:013W3910132VNCEQKQDHSNGSF-4.4836-5.5189
HLA-A11:014UQ210132VNCEQKQDHSNGSF-10.0067-10.1201
HLA-A11:014UQ210132VNCEQKQDHSNGSF-9.03915-10.0745
HLA-A24:025HGA10132VNCEQKQDHSNGSF-6.56204-6.67544
HLA-A24:025HGA10132VNCEQKQDHSNGSF-5.42271-6.45801
HLA-B44:053DX810132VNCEQKQDHSNGSF-7.85648-8.89178
HLA-B44:053DX810132VNCEQKQDHSNGSF-5.3978-5.5112
HLA-B35:011A1N10132VNCEQKQDHSNGSF-6.27422-6.38762
HLA-B35:011A1N10132VNCEQKQDHSNGSF-5.27424-6.30954
HLA-A02:016TDR10132VNCEQKQDHSNGSF-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of HOOK3-GTF2E2

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
HOOK3-GTF2E2chr842798588chr8304926401120KQDHSNGSFAGCAAGATCATAGCAATGGATCATTTA
HOOK3-GTF2E2chr842798588chr8304926401222QDHSNGSFNLAAGATCATAGCAATGGATCATTTAACTTGA
HOOK3-GTF2E2chr842798588chr830492640920EQKQDHSNGSFAACAGAAGCAAGATCATAGCAATGGATCATTTA

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 HOOK3-GTF2E2

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
STADHOOK3-GTF2E2chr842798588ENST00000307602chr830492640ENST00000355904TCGA-FP-8099-01A

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Potential target of CAR-T therapy development for HOOK3-GTF2E2

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 HOOK3-GTF2E2

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 HOOK3-GTF2E2

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
HgeneHOOK3C0032460Polycystic Ovary Syndrome1CTD_human
HgeneHOOK3C1136382Sclerocystic Ovaries1CTD_human