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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:ADD3-MXI1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADD3-MXI1
FusionPDB ID: 2309
FusionGDB2.0 ID: 2309
HgeneTgene
Gene symbol

ADD3

MXI1

Gene ID

120

4601

Gene nameadducin 3MAX interactor 1, dimerization protein
SynonymsADDL|CPSQ3MAD2|MXD2|MXI|bHLHc11
Cytomap

10q25.1-q25.2

10q25.2

Type of geneprotein-codingprotein-coding
Descriptiongamma-adducinadducin 3 (gamma)adducin-like protein 70max-interacting protein 1MAX dimerization protein 2Max-related transcription factorclass C basic helix-loop-helix protein 11
Modification date2020031320200313
UniProtAcc

Q9UEY8

Main function of 5'-partner protein: FUNCTION: Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping (PubMed:23836506). Binds to calmodulin. {ECO:0000269|PubMed:23836506}.

P50539

Main function of 5'-partner protein: FUNCTION: Transcriptional repressor. MXI1 binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. MXI1 thus antagonizes MYC transcriptional activity by competing for MAX.
Ensembl transtripts involved in fusion geneENST idsENST00000277900, ENST00000356080, 
ENST00000360162, ENST00000497125, 
ENST00000369612, ENST00000485566, 
ENST00000239007, ENST00000332674, 
ENST00000361248, ENST00000393134, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 10 X 5=65017 X 10 X 9=1530
# samples 1419
** MAII scorelog2(14/650*10)=-2.21501289097085
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(19/1530*10)=-3.00946032924907
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ADD3 [Title/Abstract] AND MXI1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADD3 [Title/Abstract] AND MXI1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADD3(111886261)-MXI1(112039671), # samples:1
ADD3(111886261)-MXI1(112039672), # samples:1
MXI1(111988079)-ADD3(111878345), # samples:2
Anticipated loss of major functional domain due to fusion event.ADD3-MXI1 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.
ADD3-MXI1 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.
MXI1-ADD3 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
MXI1-ADD3 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
MXI1-ADD3 seems lost the major protein functional domain in Tgene 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
TgeneMXI1

GO:0000122

negative regulation of transcription by RNA polymerase II

11875718



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/chr10:111886261/chr10:112039671)
- 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 ADD3 (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 MXI1 (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)
ENST00000360162ADD3chr10111886261+ENST00000332674MXI1chr10112039671+469919853772320647
ENST00000360162ADD3chr10111886261+ENST00000361248MXI1chr10112039671+384019853772320647
ENST00000360162ADD3chr10111886261+ENST00000239007MXI1chr10112039671+384019853772320647
ENST00000360162ADD3chr10111886261+ENST00000393134MXI1chr10112039671+242619853772320647
ENST00000356080ADD3chr10111886261+ENST00000332674MXI1chr10112039671+468919753672310647
ENST00000356080ADD3chr10111886261+ENST00000361248MXI1chr10112039671+383019753672310647
ENST00000356080ADD3chr10111886261+ENST00000239007MXI1chr10112039671+383019753672310647
ENST00000356080ADD3chr10111886261+ENST00000393134MXI1chr10112039671+241619753672310647
ENST00000277900ADD3chr10111886261+ENST00000332674MXI1chr10112039671+468719733652308647
ENST00000277900ADD3chr10111886261+ENST00000361248MXI1chr10112039671+382819733652308647
ENST00000277900ADD3chr10111886261+ENST00000239007MXI1chr10112039671+382819733652308647
ENST00000277900ADD3chr10111886261+ENST00000393134MXI1chr10112039671+241419733652308647
ENST00000360162ADD3chr10111886261+ENST00000332674MXI1chr10112039672+469919853772320647
ENST00000360162ADD3chr10111886261+ENST00000361248MXI1chr10112039672+384019853772320647
ENST00000360162ADD3chr10111886261+ENST00000239007MXI1chr10112039672+384019853772320647
ENST00000360162ADD3chr10111886261+ENST00000393134MXI1chr10112039672+242619853772320647
ENST00000356080ADD3chr10111886261+ENST00000332674MXI1chr10112039672+468919753672310647
ENST00000356080ADD3chr10111886261+ENST00000361248MXI1chr10112039672+383019753672310647
ENST00000356080ADD3chr10111886261+ENST00000239007MXI1chr10112039672+383019753672310647
ENST00000356080ADD3chr10111886261+ENST00000393134MXI1chr10112039672+241619753672310647
ENST00000277900ADD3chr10111886261+ENST00000332674MXI1chr10112039672+468719733652308647
ENST00000277900ADD3chr10111886261+ENST00000361248MXI1chr10112039672+382819733652308647
ENST00000277900ADD3chr10111886261+ENST00000239007MXI1chr10112039672+382819733652308647
ENST00000277900ADD3chr10111886261+ENST00000393134MXI1chr10112039672+241419733652308647

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
ENST00000360162ENST00000332674ADD3chr10111886261+MXI1chr10112039671+0.0007497650.99925023
ENST00000360162ENST00000361248ADD3chr10111886261+MXI1chr10112039671+0.0014299510.9985701
ENST00000360162ENST00000239007ADD3chr10111886261+MXI1chr10112039671+0.0014299510.9985701
ENST00000360162ENST00000393134ADD3chr10111886261+MXI1chr10112039671+0.0028624670.99713755
ENST00000356080ENST00000332674ADD3chr10111886261+MXI1chr10112039671+0.0006702220.9993298
ENST00000356080ENST00000361248ADD3chr10111886261+MXI1chr10112039671+0.0012369030.9987631
ENST00000356080ENST00000239007ADD3chr10111886261+MXI1chr10112039671+0.0012369030.9987631
ENST00000356080ENST00000393134ADD3chr10111886261+MXI1chr10112039671+0.0027606780.99723935
ENST00000277900ENST00000332674ADD3chr10111886261+MXI1chr10112039671+0.0006732590.9993267
ENST00000277900ENST00000361248ADD3chr10111886261+MXI1chr10112039671+0.0012485530.9987514
ENST00000277900ENST00000239007ADD3chr10111886261+MXI1chr10112039671+0.0012485530.9987514
ENST00000277900ENST00000393134ADD3chr10111886261+MXI1chr10112039671+0.0028460790.9971539
ENST00000360162ENST00000332674ADD3chr10111886261+MXI1chr10112039672+0.0007497650.99925023
ENST00000360162ENST00000361248ADD3chr10111886261+MXI1chr10112039672+0.0014299510.9985701
ENST00000360162ENST00000239007ADD3chr10111886261+MXI1chr10112039672+0.0014299510.9985701
ENST00000360162ENST00000393134ADD3chr10111886261+MXI1chr10112039672+0.0028624670.99713755
ENST00000356080ENST00000332674ADD3chr10111886261+MXI1chr10112039672+0.0006702220.9993298
ENST00000356080ENST00000361248ADD3chr10111886261+MXI1chr10112039672+0.0012369030.9987631
ENST00000356080ENST00000239007ADD3chr10111886261+MXI1chr10112039672+0.0012369030.9987631
ENST00000356080ENST00000393134ADD3chr10111886261+MXI1chr10112039672+0.0027606780.99723935
ENST00000277900ENST00000332674ADD3chr10111886261+MXI1chr10112039672+0.0006732590.9993267
ENST00000277900ENST00000361248ADD3chr10111886261+MXI1chr10112039672+0.0012485530.9987514
ENST00000277900ENST00000239007ADD3chr10111886261+MXI1chr10112039672+0.0012485530.9987514
ENST00000277900ENST00000393134ADD3chr10111886261+MXI1chr10112039672+0.0028460790.9971539

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 ADD3-MXI1

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 ADD3-MXI1 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 ADD3-MXI1 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 ADD3-MXI1

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 ADD3-MXI1

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 ADD3-MXI1

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 ADD3-MXI1

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 ADD3-MXI1

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 ADD3-MXI1

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 ADD3-MXI1

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
HgeneADD3C0005586Bipolar Disorder1CTD_human
HgeneADD3C0005587Depression, Bipolar1CTD_human
HgeneADD3C0007786Brain Ischemia1CTD_human
HgeneADD3C0023893Liver Cirrhosis, Experimental1CTD_human
HgeneADD3C0024713Manic Disorder1CTD_human
HgeneADD3C0149504Encephalopathy, Toxic1CTD_human
HgeneADD3C0154659Toxic Encephalitis1CTD_human
HgeneADD3C0235032Neurotoxicity Syndromes1CTD_human
HgeneADD3C0338831Manic1CTD_human
HgeneADD3C0917798Cerebral Ischemia1CTD_human
HgeneADD3C2751938Cerebral Palsy, Spastic Quadriplegic, 11ORPHANET
HgeneADD3C4310767CEREBRAL PALSY, SPASTIC QUADRIPLEGIC, 31CTD_human;GENOMICS_ENGLAND;UNIPROT