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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:SMAD3-AAGAB

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SMAD3-AAGAB
FusionPDB ID: 83788
FusionGDB2.0 ID: 83788
HgeneTgene
Gene symbol

SMAD3

AAGAB

Gene ID

4088

79719

Gene nameSMAD family member 3alpha and gamma adaptin binding protein
SynonymsHSPC193|HsT17436|JV15-2|LDS1C|LDS3|MADH3KPPP1|PPKP1|PPKP1A|p34
Cytomap

15q22.33

15q23

Type of geneprotein-codingprotein-coding
Descriptionmothers against decapentaplegic homolog 3MAD homolog 3MAD, mothers against decapentaplegic homolog 3SMA- and MAD-related protein 3SMAD, mothers against DPP homolog 3hMAD-3hSMAD3mad homolog JV15-2mad protein homologmad3mothers against DPP homologalpha- and gamma-adaptin-binding protein p34
Modification date2020032920200327
UniProtAcc.

Q6PD74

Main function of 5'-partner protein: FUNCTION: May be involved in endocytic recycling of growth factor receptors such as EGFR. {ECO:0000269|PubMed:23064416}.
Ensembl transtripts involved in fusion geneENST idsENST00000327367, ENST00000439724, 
ENST00000537194, ENST00000540846, 
ENST00000559092, 
ENST00000538028, 
ENST00000542650, ENST00000561452, 
ENST00000261880, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 13 X 12=26526 X 10 X 4=240
# samples 309
** MAII scorelog2(30/2652*10)=-3.14404636961671
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/240*10)=-1.41503749927884
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SMAD3 [Title/Abstract] AND AAGAB [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SMAD3 [Title/Abstract] AND AAGAB [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SMAD3(67358698)-AAGAB(67495236), # samples:4
AAGAB(67500900)-SMAD3(67457233), # samples:3
Anticipated loss of major functional domain due to fusion event.SMAD3-AAGAB 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.
SMAD3-AAGAB 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.
SMAD3-AAGAB 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.
SMAD3-AAGAB 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.
SMAD3-AAGAB seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
SMAD3-AAGAB seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
AAGAB-SMAD3 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
AAGAB-SMAD3 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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
HgeneSMAD3

GO:0000122

negative regulation of transcription by RNA polymerase II

8774881

HgeneSMAD3

GO:0006357

regulation of transcription by RNA polymerase II

21947082

HgeneSMAD3

GO:0007179

transforming growth factor beta receptor signaling pathway

9732876|18548003|21947082

HgeneSMAD3

GO:0007183

SMAD protein complex assembly

9111321|10823886

HgeneSMAD3

GO:0010628

positive regulation of gene expression

21307346

HgeneSMAD3

GO:0010718

positive regulation of epithelial to mesenchymal transition

21307346

HgeneSMAD3

GO:0030308

negative regulation of cell growth

8774881

HgeneSMAD3

GO:0045429

positive regulation of nitric oxide biosynthetic process

27038547

HgeneSMAD3

GO:0045599

negative regulation of fat cell differentiation

19816956

HgeneSMAD3

GO:0045893

positive regulation of transcription, DNA-templated

9111321|9311995|9732876

HgeneSMAD3

GO:0045944

positive regulation of transcription by RNA polymerase II

8774881|18832382

HgeneSMAD3

GO:0051481

negative regulation of cytosolic calcium ion concentration

27038547

HgeneSMAD3

GO:0071560

cellular response to transforming growth factor beta stimulus

12902338

HgeneSMAD3

GO:1901203

positive regulation of extracellular matrix assembly

21307346



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/chr15:67358698/chr15:67495236)
- 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 SMAD3 (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 AAGAB (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)
ENST00000327367SMAD3chr1567358698+ENST00000261880AAGABchr1567495236-23825165150172
ENST00000559092SMAD3chr1567391361+ENST00000261880AAGABchr1567529157-31064432561317353

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
ENST00000327367ENST00000261880SMAD3chr1567358698+AAGABchr1567495236-0.19974920.80025077
ENST00000559092ENST00000261880SMAD3chr1567391361+AAGABchr1567529157-0.0008617650.99913824

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 SMAD3-AAGAB

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SMAD3chr1567391361AAGABchr156752915744361QTVDRAYVLSEDQLYILGTEDLIVEV

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Potential FusionNeoAntigen Information of SMAD3-AAGAB 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.
SMAD3-AAGAB_67391361_67529157.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)
SMAD3-AAGABchr1567391361chr1567529157443HLA-B39:13SEDQLYIL0.97010.6228917
SMAD3-AAGABchr1567391361chr1567529157443HLA-A02:11VLSEDQLYI0.99690.5096716
SMAD3-AAGABchr1567391361chr1567529157443HLA-A02:21VLSEDQLYI0.99650.6255716
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:25YVLSEDQLY0.99490.8301615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:02YVLSEDQLY0.98840.8399615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:08YVLSEDQLY0.97250.7228615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:01YVLSEDQLY0.95910.7381615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:17YVLSEDQLY0.95580.737615
SMAD3-AAGABchr1567391361chr1567529157443HLA-A02:35VLSEDQLYI0.95150.5118716
SMAD3-AAGABchr1567391361chr1567529157443HLA-B13:01VLSEDQLYI0.05250.8257716
SMAD3-AAGABchr1567391361chr1567529157443HLA-A02:11VLSEDQLYIL0.99480.5107717
SMAD3-AAGABchr1567391361chr1567529157443HLA-A02:21YVLSEDQLYI0.99220.5925616
SMAD3-AAGABchr1567391361chr1567529157443HLA-A02:35VLSEDQLYIL0.9250.5086717
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:17RAYVLSEDQLY0.99760.7935415
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:16RAYVLSEDQLY0.99470.7546415
SMAD3-AAGABchr1567391361chr1567529157443HLA-B58:01RAYVLSEDQLY0.99190.8384415
SMAD3-AAGABchr1567391361chr1567529157443HLA-B39:08SEDQLYIL0.98270.5388917
SMAD3-AAGABchr1567391361chr1567529157443HLA-C08:15LSEDQLYIL0.99990.9055817
SMAD3-AAGABchr1567391361chr1567529157443HLA-C05:09LSEDQLYIL0.99990.7916817
SMAD3-AAGABchr1567391361chr1567529157443HLA-C05:09VLSEDQLYI0.99740.8433716
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:21YVLSEDQLY0.98750.8144615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:05YVLSEDQLY0.97970.7099615
SMAD3-AAGABchr1567391361chr1567529157443HLA-C04:06LSEDQLYIL0.97840.6886817
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:31YVLSEDQLY0.96120.7236615
SMAD3-AAGABchr1567391361chr1567529157443HLA-C08:04LSEDQLYIL0.88780.8826817
SMAD3-AAGABchr1567391361chr1567529157443HLA-C08:13LSEDQLYIL0.88780.8826817
SMAD3-AAGABchr1567391361chr1567529157443HLA-C04:06VLSEDQLYI0.84160.7354716
SMAD3-AAGABchr1567391361chr1567529157443HLA-C08:03LSEDQLYIL0.64350.9501817
SMAD3-AAGABchr1567391361chr1567529157443HLA-C15:04YVLSEDQLY0.51830.83615
SMAD3-AAGABchr1567391361chr1567529157443HLA-C03:14YVLSEDQLY0.2790.9692615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:05RAYVLSEDQLY0.98680.7268415
SMAD3-AAGABchr1567391361chr1567529157443HLA-B39:02SEDQLYIL0.97760.6401917
SMAD3-AAGABchr1567391361chr1567529157443HLA-C08:02LSEDQLYIL0.99990.9055817
SMAD3-AAGABchr1567391361chr1567529157443HLA-C04:03LSEDQLYIL0.99990.673817
SMAD3-AAGABchr1567391361chr1567529157443HLA-C05:01LSEDQLYIL0.99990.7916817
SMAD3-AAGABchr1567391361chr1567529157443HLA-C05:01VLSEDQLYI0.99740.8433716
SMAD3-AAGABchr1567391361chr1567529157443HLA-C04:03VLSEDQLYI0.99720.7022716
SMAD3-AAGABchr1567391361chr1567529157443HLA-A02:06VLSEDQLYI0.99650.6255716
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:39YVLSEDQLY0.99410.6819615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:11YVLSEDQLY0.98550.7921615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:20YVLSEDQLY0.98240.7881615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:28YVLSEDQLY0.9670.7767615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:77YVLSEDQLY0.95910.7381615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:12YVLSEDQLY0.95880.7433615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:23YVLSEDQLY0.95790.7388615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:20YVLSEDQLY0.9550.7837615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:27YVLSEDQLY0.94920.8466615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:11YVLSEDQLY0.93150.7498615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:08YVLSEDQLY0.93080.7351615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:135YVLSEDQLY0.92860.8152615
SMAD3-AAGABchr1567391361chr1567529157443HLA-C03:02YVLSEDQLY0.91930.9521615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:43YVLSEDQLY0.89720.7355615
SMAD3-AAGABchr1567391361chr1567529157443HLA-A25:01YVLSEDQLY0.81220.5564615
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:24YVLSEDQLY0.6490.8719615
SMAD3-AAGABchr1567391361chr1567529157443HLA-C08:01LSEDQLYIL0.64350.9501817
SMAD3-AAGABchr1567391361chr1567529157443HLA-C15:09YVLSEDQLY0.51830.83615
SMAD3-AAGABchr1567391361chr1567529157443HLA-C17:01VLSEDQLYI0.43220.5914716
SMAD3-AAGABchr1567391361chr1567529157443HLA-C02:10YVLSEDQLY0.03060.9466615
SMAD3-AAGABchr1567391361chr1567529157443HLA-C02:02YVLSEDQLY0.03060.9466615
SMAD3-AAGABchr1567391361chr1567529157443HLA-A02:06YVLSEDQLYI0.99220.5925616
SMAD3-AAGABchr1567391361chr1567529157443HLA-B35:28RAYVLSEDQLY0.98720.8214415
SMAD3-AAGABchr1567391361chr1567529157443HLA-B15:20RAYVLSEDQLY0.98580.8132415

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Potential FusionNeoAntigen Information of SMAD3-AAGAB 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 SMAD3-AAGAB

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
10846YVLSEDQLYILGTESMAD3AAGABchr1567391361chr1567529157443

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SMAD3-AAGAB

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-B14:023BVN10846YVLSEDQLYILGTE-7.9962-8.1096
HLA-B14:023BVN10846YVLSEDQLYILGTE-5.70842-6.74372
HLA-B52:013W3910846YVLSEDQLYILGTE-6.83737-6.95077
HLA-B52:013W3910846YVLSEDQLYILGTE-4.4836-5.5189
HLA-A11:014UQ210846YVLSEDQLYILGTE-10.0067-10.1201
HLA-A11:014UQ210846YVLSEDQLYILGTE-9.03915-10.0745
HLA-A24:025HGA10846YVLSEDQLYILGTE-6.56204-6.67544
HLA-A24:025HGA10846YVLSEDQLYILGTE-5.42271-6.45801
HLA-B44:053DX810846YVLSEDQLYILGTE-7.85648-8.89178
HLA-B44:053DX810846YVLSEDQLYILGTE-5.3978-5.5112
HLA-A02:016TDR10846YVLSEDQLYILGTE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SMAD3-AAGAB

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
SMAD3-AAGABchr1567391361chr1567529157415RAYVLSEDQLYCGTATGTCCTGAGCGAGGATCAACTCTATATCC
SMAD3-AAGABchr1567391361chr1567529157615YVLSEDQLYTCCTGAGCGAGGATCAACTCTATATCC
SMAD3-AAGABchr1567391361chr1567529157616YVLSEDQLYITCCTGAGCGAGGATCAACTCTATATCCTTG
SMAD3-AAGABchr1567391361chr1567529157716VLSEDQLYITGAGCGAGGATCAACTCTATATCCTTG
SMAD3-AAGABchr1567391361chr1567529157717VLSEDQLYILTGAGCGAGGATCAACTCTATATCCTTGGAA
SMAD3-AAGABchr1567391361chr1567529157817LSEDQLYILGCGAGGATCAACTCTATATCCTTGGAA
SMAD3-AAGABchr1567391361chr1567529157917SEDQLYILAGGATCAACTCTATATCCTTGGAA

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 SMAD3-AAGAB

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
BLCASMAD3-AAGABchr1567391361ENST00000559092chr1567529157ENST00000261880TCGA-GU-A42Q-01A

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Potential target of CAR-T therapy development for SMAD3-AAGAB

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 SMAD3-AAGAB

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 SMAD3-AAGAB

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