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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:DDAH1-TRABD2B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DDAH1-TRABD2B
FusionPDB ID: 21759
FusionGDB2.0 ID: 21759
HgeneTgene
Gene symbol

DDAH1

TRABD2B

Gene ID

23576

388630

Gene namedimethylarginine dimethylaminohydrolase 1TraB domain containing 2B
SynonymsDDAH|DDAH-1|DDAHI|HEL-S-16TIKI2
Cytomap

1p22.3

1p33

Type of geneprotein-codingprotein-coding
DescriptionN(G),N(G)-dimethylarginine dimethylaminohydrolase 1NG, NG-dimethylarginine dimethylaminohydrolasedimethylargininase-1epididymis secretory protein Li 16metalloprotease TIKI2TRAB domain-containing protein 2BUPF0632 protein Aheart, kidney and adipose-enriched transmembrane protein homolog
Modification date2020032020200313
UniProtAcc

O94760

Main function of 5'-partner protein: FUNCTION: Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
.
Ensembl transtripts involved in fusion geneENST idsENST00000284031, ENST00000539042, 
ENST00000426972, ENST00000483110, 
ENST00000535924, ENST00000542148, 
ENST00000435576, ENST00000606738, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 4 X 4=806 X 4 X 4=96
# samples 56
** MAII scorelog2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/96*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DDAH1 [Title/Abstract] AND TRABD2B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DDAH1 [Title/Abstract] AND TRABD2B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DDAH1(85930426)-TRABD2B(48267291), # samples:2
Anticipated loss of major functional domain due to fusion event.DDAH1-TRABD2B 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.
DDAH1-TRABD2B 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.
DDAH1-TRABD2B 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.
DDAH1-TRABD2B 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
HgeneDDAH1

GO:0000052

citrulline metabolic process

19663506

HgeneDDAH1

GO:0006527

arginine catabolic process

24895913

HgeneDDAH1

GO:0008285

negative regulation of cell proliferation

24895913

HgeneDDAH1

GO:0043116

negative regulation of vascular permeability

24895913

HgeneDDAH1

GO:1900038

negative regulation of cellular response to hypoxia

24895913

TgeneTRABD2B

GO:0006508

proteolysis

22726442

TgeneTRABD2B

GO:0030178

negative regulation of Wnt signaling pathway

22726442

TgeneTRABD2B

GO:0031334

positive regulation of protein complex assembly

22726442

TgeneTRABD2B

GO:1904808

positive regulation of protein oxidation

22726442



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/chr1:85930426/chr1:48267291)
- 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 DDAH1 (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 TRABD2B (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)
ENST00000284031DDAH1chr185930426-ENST00000606738TRABD2Bchr148267291-6660398951285396
ENST00000539042DDAH1chr185930426-ENST00000606738TRABD2Bchr148267291-6664402991289396

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
ENST00000284031ENST00000606738DDAH1chr185930426-TRABD2Bchr148267291-0.0203799830.97962004
ENST00000539042ENST00000606738DDAH1chr185930426-TRABD2Bchr148267291-0.020459770.9795402

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 DDAH1-TRABD2B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DDAH1chr185930426TRABD2Bchr14826729139893AVVCEETALITRPGAPSRRKEVLFAL
DDAH1chr185930426TRABD2Bchr14826729140293AVVCEETALITRPGAPSRRKEVLFAL

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Potential FusionNeoAntigen Information of DDAH1-TRABD2B 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.
DDAH1-TRABD2B_85930426_48267291.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)
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A30:08ITRPGAPSR0.99350.7995918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A74:09ITRPGAPSR0.9720.7345918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A74:03ITRPGAPSR0.9720.7345918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A74:11ITRPGAPSR0.9720.7345918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A31:02ITRPGAPSR0.96890.7724918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A66:01ITRPGAPSR0.95310.5433918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A68:08ITRPGAPSR0.95030.581918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A31:06ITRPGAPSR0.92910.5976918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A66:03ITRPGAPSR0.84760.6571918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-B07:02RPGAPSRRKEV0.99960.6051122
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A30:08ITRPGAPSRRK0.99280.8539920
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A74:03ALITRPGAPSR0.99090.7846718
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A74:09ALITRPGAPSR0.99090.7846718
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A74:11ALITRPGAPSR0.99090.7846718
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A03:12ITRPGAPSRRK0.98740.5873920
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A31:02ALITRPGAPSR0.98690.8041718
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A31:06ALITRPGAPSR0.97870.5979718
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A31:01ITRPGAPSR0.97970.734918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A31:01ITRPGAPSRR0.96260.7966919
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A33:03ITRPGAPSRR0.95720.5822919
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A31:01ALITRPGAPSR0.99350.7745718
DDAH1-TRABD2Bchr185930426chr148267291398HLA-B07:04RPGAPSRRKEV0.98990.52041122
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A30:01ITRPGAPSR0.99370.908918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A74:01ITRPGAPSR0.9720.7345918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A66:02ITRPGAPSR0.90430.6447918
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A68:02ETALITRPGA0.99080.6185515
DDAH1-TRABD2Bchr185930426chr148267291398HLA-B07:22RPGAPSRRKEV0.99960.6051122
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A74:01ALITRPGAPSR0.99090.7846718
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A30:01ITRPGAPSRRK0.98830.9401920
DDAH1-TRABD2Bchr185930426chr148267291398HLA-A30:01ALITRPGAPSR0.98740.9118718

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Potential FusionNeoAntigen Information of DDAH1-TRABD2B 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 DDAH1-TRABD2B

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
9230TALITRPGAPSRRKDDAH1TRABD2Bchr185930426chr148267291398

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DDAH1-TRABD2B

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-B14:023BVN9230TALITRPGAPSRRK-7.9962-8.1096
HLA-B14:023BVN9230TALITRPGAPSRRK-5.70842-6.74372
HLA-B52:013W399230TALITRPGAPSRRK-6.83737-6.95077
HLA-B52:013W399230TALITRPGAPSRRK-4.4836-5.5189
HLA-A11:014UQ29230TALITRPGAPSRRK-10.0067-10.1201
HLA-A11:014UQ29230TALITRPGAPSRRK-9.03915-10.0745
HLA-A24:025HGA9230TALITRPGAPSRRK-6.56204-6.67544
HLA-A24:025HGA9230TALITRPGAPSRRK-5.42271-6.45801
HLA-B44:053DX89230TALITRPGAPSRRK-7.85648-8.89178
HLA-B44:053DX89230TALITRPGAPSRRK-5.3978-5.5112
HLA-A02:016TDR9230TALITRPGAPSRRK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of DDAH1-TRABD2B

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
DDAH1-TRABD2Bchr185930426chr1482672911122RPGAPSRRKEVAAGGAGGTGCTGTTTGCCCTGAACCAAACCCTG
DDAH1-TRABD2Bchr185930426chr148267291515ETALITRPGAGGGGCGCCGAGCCGGAGGAAGGAGGTGCTG
DDAH1-TRABD2Bchr185930426chr148267291718ALITRPGAPSRCCGAGCCGGAGGAAGGAGGTGCTGTTTGCCCTG
DDAH1-TRABD2Bchr185930426chr148267291918ITRPGAPSRCGGAGGAAGGAGGTGCTGTTTGCCCTG
DDAH1-TRABD2Bchr185930426chr148267291919ITRPGAPSRRCGGAGGAAGGAGGTGCTGTTTGCCCTGAAC
DDAH1-TRABD2Bchr185930426chr148267291920ITRPGAPSRRKCGGAGGAAGGAGGTGCTGTTTGCCCTGAACCAA

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 DDAH1-TRABD2B

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
COADDDAH1-TRABD2Bchr185930426ENST00000284031chr148267291ENST00000606738TCGA-DM-A0XF-01A

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Potential target of CAR-T therapy development for DDAH1-TRABD2B

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
TgeneTRABD2Bchr1:85930426chr1:48267291ENST0000060673817495_5150518.0TransmembraneHelical

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 DDAH1-TRABD2B

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 DDAH1-TRABD2B

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