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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-BAALC

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HOOK3-BAALC
FusionPDB ID: 37383
FusionGDB2.0 ID: 37383
HgeneTgene
Gene symbol

HOOK3

BAALC

Gene ID

84376

79870

Gene namehook microtubule tethering protein 3BAALC binder of MAP3K1 and KLF4
SynonymsHK3-
Cytomap

8p11.21

8q22.3

Type of geneprotein-codingprotein-coding
Descriptionprotein Hook homolog 3h-hook3hHK3hook homolog 3brain and acute leukemia cytoplasmic proteinBAALC, MAP3K1 and KLF4 bindingBAALC, MEKK1 and KLF4 bindingbrain and acute leukemia, cytoplasmic
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}.

Q8WXS3

Main function of 5'-partner protein: FUNCTION: May play a synaptic role at the postsynaptic lipid rafts possibly through interaction with CAMK2A. {ECO:0000250|UniProtKB:Q920K5}.
Ensembl transtripts involved in fusion geneENST idsENST00000307602, ENST00000524839, 
ENST00000523754, ENST00000297574, 
ENST00000306391, ENST00000330955, 
ENST00000438105, ENST00000309982, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 13 X 9=18726 X 2 X 4=48
# samples 196
** MAII scorelog2(19/1872*10)=-3.30050911125246
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/48*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HOOK3(42780772)-BAALC(104225147), # samples:3
Anticipated loss of major functional domain due to fusion event.HOOK3-BAALC 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-BAALC 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-BAALC 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-BAALC 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-BAALC seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
HOOK3-BAALC seems lost the major protein functional domain in Hgene partner, which is a essential gene 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


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/chr8:42780772/chr8:104225147)
- 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 BAALC (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)
ENST00000307602HOOK3chr842780772+ENST00000309982BAALCchr8104240217+2732416182526114

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
ENST00000307602ENST00000309982HOOK3chr842780772+BAALCchr8104240217+0.0075653670.9924346

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-BAALC

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HOOK3chr842780772BAALCchr810424021741678RIKTEVGDNWRLKAKRDAKRMPAKEV

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Potential FusionNeoAntigen Information of HOOK3-BAALC 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-BAALC_42780772_104240217.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-BAALCchr842780772chr8104240217416HLA-A30:08RLKAKRDAK0.99090.58051019
HOOK3-BAALCchr842780772chr8104240217416HLA-A30:01RLKAKRDAK0.9920.76151019

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Potential FusionNeoAntigen Information of HOOK3-BAALC 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.
HOOK3-BAALC_42780772_104240217.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)
HOOK3-BAALCchr842780772chr8104240217416DRB1-1111VGDNWRLKAKRDAKR520
HOOK3-BAALCchr842780772chr8104240217416DRB1-1111GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1111EVGDNWRLKAKRDAK419
HOOK3-BAALCchr842780772chr8104240217416DRB1-1111DNWRLKAKRDAKRMP722
HOOK3-BAALCchr842780772chr8104240217416DRB1-1114GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1120GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1132VGDNWRLKAKRDAKR520
HOOK3-BAALCchr842780772chr8104240217416DRB1-1132GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1168GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1168VGDNWRLKAKRDAKR520
HOOK3-BAALCchr842780772chr8104240217416DRB1-1172GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1172VGDNWRLKAKRDAKR520
HOOK3-BAALCchr842780772chr8104240217416DRB1-1186GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1186VGDNWRLKAKRDAKR520
HOOK3-BAALCchr842780772chr8104240217416DRB1-1302GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1316GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1316VGDNWRLKAKRDAKR520
HOOK3-BAALCchr842780772chr8104240217416DRB1-1323GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1329GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1329VGDNWRLKAKRDAKR520
HOOK3-BAALCchr842780772chr8104240217416DRB1-1334GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1336GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1336VGDNWRLKAKRDAKR520
HOOK3-BAALCchr842780772chr8104240217416DRB1-1339GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1363VGDNWRLKAKRDAKR520
HOOK3-BAALCchr842780772chr8104240217416DRB1-1363GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1363EVGDNWRLKAKRDAK419
HOOK3-BAALCchr842780772chr8104240217416DRB1-1363DNWRLKAKRDAKRMP722
HOOK3-BAALCchr842780772chr8104240217416DRB1-1373GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1374GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1397GDNWRLKAKRDAKRM621
HOOK3-BAALCchr842780772chr8104240217416DRB1-1399GDNWRLKAKRDAKRM621

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Fusion breakpoint peptide structures of HOOK3-BAALC

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
2715GDNWRLKAKRDAKRHOOK3BAALCchr842780772chr8104240217416

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

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-B14:023BVN2715GDNWRLKAKRDAKR-7.15543-7.26883
HLA-B14:023BVN2715GDNWRLKAKRDAKR-4.77435-5.80965
HLA-B52:013W392715GDNWRLKAKRDAKR-6.80875-6.92215
HLA-B52:013W392715GDNWRLKAKRDAKR-4.20386-5.23916
HLA-A11:014UQ22715GDNWRLKAKRDAKR-7.5194-8.5547
HLA-A11:014UQ22715GDNWRLKAKRDAKR-6.9601-7.0735
HLA-A24:025HGA2715GDNWRLKAKRDAKR-7.52403-7.63743
HLA-A24:025HGA2715GDNWRLKAKRDAKR-5.82433-6.85963
HLA-B27:056PYJ2715GDNWRLKAKRDAKR-3.28285-4.31815
HLA-B44:053DX82715GDNWRLKAKRDAKR-5.91172-6.94702
HLA-B44:053DX82715GDNWRLKAKRDAKR-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of HOOK3-BAALC

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-BAALCchr842780772chr81042402171019RLKAKRDAKAGGCTAAAGGCTAAAAGAGATGCTAAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
HOOK3-BAALCchr842780772chr8104240217419EVGDNWRLKAKRDAKGAAGTAGGAGATAATTGGAGGCTAAAGGCTAAAAGAGATGCTAAG
HOOK3-BAALCchr842780772chr8104240217520VGDNWRLKAKRDAKRGTAGGAGATAATTGGAGGCTAAAGGCTAAAAGAGATGCTAAGAGA
HOOK3-BAALCchr842780772chr8104240217621GDNWRLKAKRDAKRMGGAGATAATTGGAGGCTAAAGGCTAAAAGAGATGCTAAGAGAATG
HOOK3-BAALCchr842780772chr8104240217722DNWRLKAKRDAKRMPGATAATTGGAGGCTAAAGGCTAAAAGAGATGCTAAGAGAATGCCT

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Information of the samples that have these potential fusion neoantigens of HOOK3-BAALC

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
BLCAHOOK3-BAALCchr842780772ENST00000307602chr8104240217ENST00000309982TCGA-K4-A6MB-01A

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

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-BAALC

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-BAALC

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