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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:IRX1-ADAMTS16

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: IRX1-ADAMTS16
FusionPDB ID: 40285
FusionGDB2.0 ID: 40285
HgeneTgene
Gene symbol

IRX1

ADAMTS16

Gene ID

79192

170690

Gene nameiroquois homeobox 1ADAM metallopeptidase with thrombospondin type 1 motif 16
SynonymsIRX-5|IRXA1ADAMTS16s
Cytomap

5p15.33

5p15.32

Type of geneprotein-codingprotein-coding
Descriptioniroquois-class homeodomain protein IRX-1homeodomain protein IRXA1iroquois homeobox protein 1A disintegrin and metalloproteinase with thrombospondin motifs 16ADAM-TS 16ADAM-TS16ADAMTS-16a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 16
Modification date2020031320200313
UniProtAcc

P78414

Main function of 5'-partner protein:

Q8TE57

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000302006, ENST00000513709, 
ENST00000274181, ENST00000511368, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score1 X 1 X 1=14 X 6 X 3=72
# samples 15
** MAII scorelog2(1/1*10)=3.32192809488736log2(5/72*10)=-0.526068811667588
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: IRX1 [Title/Abstract] AND ADAMTS16 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: IRX1 [Title/Abstract] AND ADAMTS16 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)IRX1(3596495)-ADAMTS16(5182157), # samples:3
Anticipated loss of major functional domain due to fusion event.IRX1-ADAMTS16 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.
IRX1-ADAMTS16 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.
IRX1-ADAMTS16 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.
IRX1-ADAMTS16 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
HgeneIRX1

GO:0000122

negative regulation of transcription by RNA polymerase II

20440264



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/chr5:3596495/chr5:5182157)
- 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 IRX1 (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 ADAMTS16 (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)
ENST00000302006IRX1chr53596495+ENST00000274181ADAMTS16chr55182157+46683285235011149
ENST00000302006IRX1chr53596495+ENST00000511368ADAMTS16chr55182157+2371328521539495

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
ENST00000302006ENST00000274181IRX1chr53596495+ADAMTS16chr55182157+0.0018536940.9981463
ENST00000302006ENST00000511368IRX1chr53596495+ADAMTS16chr55182157+0.0052323770.99476767

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 IRX1-ADAMTS16

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
IRX1chr53596495ADAMTS16chr5518215732892LPYAADLSLFSQMSGMIRTEEADYFL

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Potential FusionNeoAntigen Information of IRX1-ADAMTS16 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.
IRX1-ADAMTS16_3596495_5182157.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)
IRX1-ADAMTS16chr53596495chr55182157328HLA-A02:22SLFSQMSGM0.93390.7401716
IRX1-ADAMTS16chr53596495chr55182157328HLA-A02:38SLFSQMSGM0.87980.8031716
IRX1-ADAMTS16chr53596495chr55182157328HLA-A02:13SLFSQMSGM0.85430.8099716
IRX1-ADAMTS16chr53596495chr55182157328HLA-A02:11SLFSQMSGM0.84380.7115716
IRX1-ADAMTS16chr53596495chr55182157328HLA-A02:04SLFSQMSGM0.76490.7355716
IRX1-ADAMTS16chr53596495chr55182157328HLA-A02:17SLFSQMSGM0.73520.6453716
IRX1-ADAMTS16chr53596495chr55182157328HLA-A02:21SQMSGMIRT0.50440.65231019
IRX1-ADAMTS16chr53596495chr55182157328HLA-A74:03SLFSQMSGMIR0.95280.6567718
IRX1-ADAMTS16chr53596495chr55182157328HLA-A74:09SLFSQMSGMIR0.95280.6567718
IRX1-ADAMTS16chr53596495chr55182157328HLA-A74:11SLFSQMSGMIR0.95280.6567718
IRX1-ADAMTS16chr53596495chr55182157328HLA-B15:04SLFSQMSGM0.82990.9654716
IRX1-ADAMTS16chr53596495chr55182157328HLA-A02:03SLFSQMSGM0.91640.8016716
IRX1-ADAMTS16chr53596495chr55182157328HLA-B15:73SLFSQMSGM0.70890.9715716
IRX1-ADAMTS16chr53596495chr55182157328HLA-B15:30SLFSQMSGM0.61960.8959716
IRX1-ADAMTS16chr53596495chr55182157328HLA-A02:06SQMSGMIRT0.50440.65231019
IRX1-ADAMTS16chr53596495chr55182157328HLA-A74:01SLFSQMSGMIR0.95280.6567718

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Potential FusionNeoAntigen Information of IRX1-ADAMTS16 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 IRX1-ADAMTS16

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
5640LSLFSQMSGMIRTEIRX1ADAMTS16chr53596495chr55182157328

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of IRX1-ADAMTS16

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-B14:023BVN5640LSLFSQMSGMIRTE-8.85616-8.96956
HLA-B14:023BVN5640LSLFSQMSGMIRTE-5.66423-6.69953
HLA-B52:013W395640LSLFSQMSGMIRTE-6.49489-6.60829
HLA-B52:013W395640LSLFSQMSGMIRTE-3.99785-5.03315
HLA-A11:014UQ25640LSLFSQMSGMIRTE-4.90759-5.94289
HLA-A24:025HGA5640LSLFSQMSGMIRTE-7.27887-7.39227
HLA-A24:025HGA5640LSLFSQMSGMIRTE-7.11524-8.15054
HLA-B27:056PYJ5640LSLFSQMSGMIRTE-6.11615-6.22955
HLA-B27:056PYJ5640LSLFSQMSGMIRTE-4.78818-5.82348
HLA-B44:053DX85640LSLFSQMSGMIRTE-7.22602-7.33942
HLA-B44:053DX85640LSLFSQMSGMIRTE-4.86671-5.90201

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Vaccine Design for the FusionNeoAntigens of IRX1-ADAMTS16

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
IRX1-ADAMTS16chr53596495chr551821571019SQMSGMIRTTCGCAGATGTCAGGCATGATACGAACA
IRX1-ADAMTS16chr53596495chr55182157716SLFSQMSGMAGCCTCTTCTCGCAGATGTCAGGCATG
IRX1-ADAMTS16chr53596495chr55182157718SLFSQMSGMIRAGCCTCTTCTCGCAGATGTCAGGCATGATACGA

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 IRX1-ADAMTS16

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
SKCMIRX1-ADAMTS16chr53596495ENST00000302006chr55182157ENST00000274181TCGA-BF-AAP6-01A

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Potential target of CAR-T therapy development for IRX1-ADAMTS16

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 IRX1-ADAMTS16

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 IRX1-ADAMTS16

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