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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:TRA2A-AQP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRA2A-AQP1
FusionPDB ID: 93572
FusionGDB2.0 ID: 93572
HgeneTgene
Gene symbol

TRA2A

AQP1

Gene ID

29896

84182

Gene nametransformer 2 alpha homologMINDY lysine 48 deubiquitinase 4
SynonymsAWMS1|HSU53209AQP-1|AQP1|C7orf67|CHIP28|FAM188B
Cytomap

7p15.3

7p14.3

Type of geneprotein-codingprotein-coding
Descriptiontransformer-2 protein homolog alphaTRA-2 alphaTRA2-alphaTra2alphahtra-2 alphaputative MAPK activating protein PM24transformer-2 alphatransformer-2 protein homolog Aprobable ubiquitin carboxyl-terminal hydrolase MINDY-4Aquaporin-1Aquaporin-CHIPMINDY deubiquitinase 4Urine water channelWater channel protein for red blood cells and kidney proximal tubulefamily with sequence similarity 188 member Bprobable deubiqu
Modification date2020031320200313
UniProtAcc.

Q8NBQ7

Main function of 5'-partner protein: FUNCTION: Channel protein that facilitates the transport of water, glycerol and hydrogen peroxide across membrane of cell or organelles guaranteeing intracellular homeostasis in several organes like liver, kidney and brain (PubMed:24845055, PubMed:24918044, PubMed:31546170). In situation of stress, participates in endoplasmic reticulum (ER) homeostasis by regulating redox homeostasis through the transport of hydrogen peroxide across the endoplasmic reticulum membrane thereby regulating the oxidative stress through the NADPH oxidase 2 pathway (PubMed:31546170). Plays a role by maintaining an environment suitable for translation or protein foldings in the ER lumen namely by participating in the PKD1 glycosylation processing resulting in regulation of PKD1 membrane trafficking thereby preventing the accumulation of unfolding protein in ER (By similarity). Plays a role in the proximal tubule function by regulating its endosomal acidification (By similarity). May play a role in postnatal kidney development (By similarity). {ECO:0000250|UniProtKB:Q8BHH1, ECO:0000269|PubMed:24845055, ECO:0000269|PubMed:24918044, ECO:0000269|PubMed:31546170}.
Ensembl transtripts involved in fusion geneENST idsENST00000297071, ENST00000392502, 
ENST00000538367, ENST00000474586, 
ENST00000409611, ENST00000409899, 
ENST00000441328, ENST00000482461, 
ENST00000311813, ENST00000434909, 
ENST00000509504, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score20 X 14 X 9=25205 X 7 X 3=105
# samples 246
** MAII scorelog2(24/2520*10)=-3.39231742277876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(6/105*10)=-0.807354922057604
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TRA2A [Title/Abstract] AND AQP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TRA2A [Title/Abstract] AND AQP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRA2A(23571408)-AQP1(30961681), # samples:3
Anticipated loss of major functional domain due to fusion event.TRA2A-AQP1 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.
TRA2A-AQP1 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.
TRA2A-AQP1 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.
TRA2A-AQP1 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
HgeneTRA2A

GO:0000398

mRNA splicing, via spliceosome

9546399



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/chr7:23571408/chr7:30961681)
- 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 TRA2A (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 AQP1 (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)
ENST00000297071TRA2Achr723571408-ENST00000434909AQP1chr730961681+862253217678153
ENST00000297071TRA2Achr723571408-ENST00000509504AQP1chr730961681+862253217678153
ENST00000297071TRA2Achr723571408-ENST00000311813AQP1chr730961681+2566253217678153
ENST00000297071TRA2Achr723571407-ENST00000434909AQP1chr730961680+862253217678153
ENST00000297071TRA2Achr723571407-ENST00000509504AQP1chr730961680+862253217678153
ENST00000297071TRA2Achr723571407-ENST00000311813AQP1chr730961680+2566253217678153

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
ENST00000297071ENST00000434909TRA2Achr723571408-AQP1chr730961681+0.0073475020.9926524
ENST00000297071ENST00000509504TRA2Achr723571408-AQP1chr730961681+0.0073475020.9926524
ENST00000297071ENST00000311813TRA2Achr723571408-AQP1chr730961681+0.0137676220.9862324
ENST00000297071ENST00000434909TRA2Achr723571407-AQP1chr730961680+0.0073475020.9926524
ENST00000297071ENST00000509504TRA2Achr723571407-AQP1chr730961680+0.0073475020.9926524
ENST00000297071ENST00000311813TRA2Achr723571407-AQP1chr730961680+0.0137676220.9862324

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 TRA2A-AQP1

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 TRA2A-AQP1 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 TRA2A-AQP1 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 TRA2A-AQP1

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 TRA2A-AQP1

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 TRA2A-AQP1

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 TRA2A-AQP1

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 TRA2A-AQP1

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
TgeneAQP1chr7:23571407chr7:30961680ENST0000031181304187_1920270.0Intramembrane.
TgeneAQP1chr7:23571407chr7:30961680ENST0000031181304193_2000270.0IntramembraneNote=Helical%3B Name%3DHelix E
TgeneAQP1chr7:23571407chr7:30961680ENST0000040961104187_1920219.0Intramembrane.
TgeneAQP1chr7:23571407chr7:30961680ENST0000040961104193_2000219.0IntramembraneNote=Helical%3B Name%3DHelix E
TgeneAQP1chr7:23571407chr7:30961680ENST000004096110477_840219.0IntramembraneNote=Helical%3B Name%3DHelix B
TgeneAQP1chr7:23571407chr7:30961680ENST0000040989904187_1920155.0Intramembrane.
TgeneAQP1chr7:23571407chr7:30961680ENST0000040989904193_2000155.0IntramembraneNote=Helical%3B Name%3DHelix E
TgeneAQP1chr7:23571407chr7:30961680ENST000004098990471_760155.0Intramembrane.
TgeneAQP1chr7:23571407chr7:30961680ENST000004098990477_840155.0IntramembraneNote=Helical%3B Name%3DHelix B
TgeneAQP1chr7:23571407chr7:30961680ENST0000044132815187_1920187.0Intramembrane.
TgeneAQP1chr7:23571407chr7:30961680ENST0000044132815193_2000187.0IntramembraneNote=Helical%3B Name%3DHelix E
TgeneAQP1chr7:23571407chr7:30961680ENST000004413281571_760187.0Intramembrane.
TgeneAQP1chr7:23571407chr7:30961680ENST000004413281577_840187.0IntramembraneNote=Helical%3B Name%3DHelix B
TgeneAQP1chr7:23571408chr7:30961681ENST0000031181304187_1920270.0Intramembrane.
TgeneAQP1chr7:23571408chr7:30961681ENST0000031181304193_2000270.0IntramembraneNote=Helical%3B Name%3DHelix E
TgeneAQP1chr7:23571408chr7:30961681ENST0000040961104187_1920219.0Intramembrane.
TgeneAQP1chr7:23571408chr7:30961681ENST0000040961104193_2000219.0IntramembraneNote=Helical%3B Name%3DHelix E
TgeneAQP1chr7:23571408chr7:30961681ENST000004096110477_840219.0IntramembraneNote=Helical%3B Name%3DHelix B
TgeneAQP1chr7:23571408chr7:30961681ENST0000040989904187_1920155.0Intramembrane.
TgeneAQP1chr7:23571408chr7:30961681ENST0000040989904193_2000155.0IntramembraneNote=Helical%3B Name%3DHelix E
TgeneAQP1chr7:23571408chr7:30961681ENST000004098990471_760155.0Intramembrane.
TgeneAQP1chr7:23571408chr7:30961681ENST000004098990477_840155.0IntramembraneNote=Helical%3B Name%3DHelix B
TgeneAQP1chr7:23571408chr7:30961681ENST0000044132815187_1920187.0Intramembrane.
TgeneAQP1chr7:23571408chr7:30961681ENST0000044132815193_2000187.0IntramembraneNote=Helical%3B Name%3DHelix E
TgeneAQP1chr7:23571408chr7:30961681ENST000004413281571_760187.0Intramembrane.
TgeneAQP1chr7:23571408chr7:30961681ENST000004413281577_840187.0IntramembraneNote=Helical%3B Name%3DHelix B
TgeneAQP1chr7:23571407chr7:30961680ENST0000031181304137_1550270.0TransmembraneNote=Helical%3B Name%3DHelix 4
TgeneAQP1chr7:23571407chr7:30961680ENST0000031181304167_1830270.0TransmembraneNote=Helical%3B Name%3DHelix 5
TgeneAQP1chr7:23571407chr7:30961680ENST0000031181304208_2280270.0TransmembraneNote=Helical%3B Name%3DHelix 6
TgeneAQP1chr7:23571407chr7:30961680ENST0000040961104137_1550219.0TransmembraneNote=Helical%3B Name%3DHelix 4
TgeneAQP1chr7:23571407chr7:30961680ENST0000040961104167_1830219.0TransmembraneNote=Helical%3B Name%3DHelix 5
TgeneAQP1chr7:23571407chr7:30961680ENST0000040961104208_2280219.0TransmembraneNote=Helical%3B Name%3DHelix 6
TgeneAQP1chr7:23571407chr7:30961680ENST000004096110495_1150219.0TransmembraneNote=Helical%3B Name%3DHelix 3
TgeneAQP1chr7:23571407chr7:30961680ENST0000040989904137_1550155.0TransmembraneNote=Helical%3B Name%3DHelix 4
TgeneAQP1chr7:23571407chr7:30961680ENST0000040989904167_1830155.0TransmembraneNote=Helical%3B Name%3DHelix 5
TgeneAQP1chr7:23571407chr7:30961680ENST0000040989904208_2280155.0TransmembraneNote=Helical%3B Name%3DHelix 6
TgeneAQP1chr7:23571407chr7:30961680ENST000004098990449_660155.0TransmembraneNote=Helical%3B Name%3DHelix 2
TgeneAQP1chr7:23571407chr7:30961680ENST000004098990495_1150155.0TransmembraneNote=Helical%3B Name%3DHelix 3
TgeneAQP1chr7:23571407chr7:30961680ENST0000044132815137_1550187.0TransmembraneNote=Helical%3B Name%3DHelix 4
TgeneAQP1chr7:23571407chr7:30961680ENST0000044132815167_1830187.0TransmembraneNote=Helical%3B Name%3DHelix 5
TgeneAQP1chr7:23571407chr7:30961680ENST0000044132815208_2280187.0TransmembraneNote=Helical%3B Name%3DHelix 6
TgeneAQP1chr7:23571407chr7:30961680ENST000004413281549_660187.0TransmembraneNote=Helical%3B Name%3DHelix 2
TgeneAQP1chr7:23571407chr7:30961680ENST000004413281595_1150187.0TransmembraneNote=Helical%3B Name%3DHelix 3
TgeneAQP1chr7:23571408chr7:30961681ENST0000031181304137_1550270.0TransmembraneNote=Helical%3B Name%3DHelix 4
TgeneAQP1chr7:23571408chr7:30961681ENST0000031181304167_1830270.0TransmembraneNote=Helical%3B Name%3DHelix 5
TgeneAQP1chr7:23571408chr7:30961681ENST0000031181304208_2280270.0TransmembraneNote=Helical%3B Name%3DHelix 6
TgeneAQP1chr7:23571408chr7:30961681ENST0000040961104137_1550219.0TransmembraneNote=Helical%3B Name%3DHelix 4
TgeneAQP1chr7:23571408chr7:30961681ENST0000040961104167_1830219.0TransmembraneNote=Helical%3B Name%3DHelix 5
TgeneAQP1chr7:23571408chr7:30961681ENST0000040961104208_2280219.0TransmembraneNote=Helical%3B Name%3DHelix 6
TgeneAQP1chr7:23571408chr7:30961681ENST000004096110495_1150219.0TransmembraneNote=Helical%3B Name%3DHelix 3
TgeneAQP1chr7:23571408chr7:30961681ENST0000040989904137_1550155.0TransmembraneNote=Helical%3B Name%3DHelix 4
TgeneAQP1chr7:23571408chr7:30961681ENST0000040989904167_1830155.0TransmembraneNote=Helical%3B Name%3DHelix 5
TgeneAQP1chr7:23571408chr7:30961681ENST0000040989904208_2280155.0TransmembraneNote=Helical%3B Name%3DHelix 6
TgeneAQP1chr7:23571408chr7:30961681ENST000004098990449_660155.0TransmembraneNote=Helical%3B Name%3DHelix 2
TgeneAQP1chr7:23571408chr7:30961681ENST000004098990495_1150155.0TransmembraneNote=Helical%3B Name%3DHelix 3
TgeneAQP1chr7:23571408chr7:30961681ENST0000044132815137_1550187.0TransmembraneNote=Helical%3B Name%3DHelix 4
TgeneAQP1chr7:23571408chr7:30961681ENST0000044132815167_1830187.0TransmembraneNote=Helical%3B Name%3DHelix 5
TgeneAQP1chr7:23571408chr7:30961681ENST0000044132815208_2280187.0TransmembraneNote=Helical%3B Name%3DHelix 6
TgeneAQP1chr7:23571408chr7:30961681ENST000004413281549_660187.0TransmembraneNote=Helical%3B Name%3DHelix 2
TgeneAQP1chr7:23571408chr7:30961681ENST000004413281595_1150187.0TransmembraneNote=Helical%3B Name%3DHelix 3

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 TRA2A-AQP1

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 TRA2A-AQP1

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