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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:CDH1-ALDH3A2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CDH1-ALDH3A2
FusionPDB ID: 15027
FusionGDB2.0 ID: 15027
HgeneTgene
Gene symbol

CDH1

ALDH3A2

Gene ID

51343

224

Gene namefizzy and cell division cycle 20 related 1aldehyde dehydrogenase 3 family member A2
SynonymsCDC20C|CDH1|FZR|FZR2|HCDH|HCDH1ALDH10|FALDH|SLS
Cytomap

19p13.3

17p11.2

Type of geneprotein-codingprotein-coding
Descriptionfizzy-related protein homologCDC20 homolog 1CDC20-like 1bCDC20-like protein 1cdh1/Hct1 homologfizzy/cell division cycle 20 related 1aldehyde dehydrogenase family 3 member A2aldehyde dehydrogenase 10fatty aldehyde dehydrogenasemicrosomal aldehyde dehydrogenase
Modification date2020031320200315
UniProtAcc

Q9H159

Main function of 5'-partner protein: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.

P51648

Main function of 5'-partner protein: FUNCTION: Catalyzes the oxidation of medium and long chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length (PubMed:9133646, PubMed:22633490, PubMed:25047030, PubMed:18035827, PubMed:9662422, PubMed:18182499). Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid (PubMed:22633490). {ECO:0000269|PubMed:18035827, ECO:0000269|PubMed:18182499, ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:25047030, ECO:0000269|PubMed:9133646, ECO:0000269|PubMed:9662422}.
Ensembl transtripts involved in fusion geneENST idsENST00000261769, ENST00000422392, 
ENST00000562836, 
ENST00000339618, 
ENST00000395575, ENST00000571163, 
ENST00000574597, ENST00000579855, 
ENST00000581518, ENST00000176643, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score21 X 16 X 8=26885 X 6 X 4=120
# samples 295
** MAII scorelog2(29/2688*10)=-3.21240833276383
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/120*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CDH1 [Title/Abstract] AND ALDH3A2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CDH1 [Title/Abstract] AND ALDH3A2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CDH1(68772314)-ALDH3A2(19578870), # samples:1
CDH1(68772314)-ALDH3A2(19578871), # samples:1
Anticipated loss of major functional domain due to fusion event.CDH1-ALDH3A2 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.
CDH1-ALDH3A2 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
HgeneCDH1

GO:0031145

anaphase-promoting complex-dependent catabolic process

18662541|21596315

HgeneCDH1

GO:0072425

signal transduction involved in G2 DNA damage checkpoint

18662541

HgeneCDH1

GO:1904668

positive regulation of ubiquitin protein ligase activity

11459826

TgeneALDH3A2

GO:0006081

cellular aldehyde metabolic process

9133646

TgeneALDH3A2

GO:0046458

hexadecanal metabolic process

25047030

TgeneALDH3A2

GO:0055114

oxidation-reduction process

9133646



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/chr16:68772314/chr17:19578870)
- 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 CDH1 (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 ALDH3A2 (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)
ENST00000261769CDH1chr1668772314+ENST00000176643ALDH3A2chr1719578870+239335441421126
ENST00000422392CDH1chr1668772314+ENST00000176643ALDH3A2chr1719578870+22662276429476
ENST00000261769CDH1chr1668772314+ENST00000176643ALDH3A2chr1719578871+239335441421126
ENST00000422392CDH1chr1668772314+ENST00000176643ALDH3A2chr1719578871+22662276429476

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
ENST00000261769ENST00000176643CDH1chr1668772314+ALDH3A2chr1719578870+0.464464780.5355352
ENST00000422392ENST00000176643CDH1chr1668772314+ALDH3A2chr1719578870+0.74918970.2508103
ENST00000261769ENST00000176643CDH1chr1668772314+ALDH3A2chr1719578871+0.464464780.5355352
ENST00000422392ENST00000176643CDH1chr1668772314+ALDH3A2chr1719578871+0.74918970.2508103

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 CDH1-ALDH3A2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CDH1chr1668772314ALDH3A2chr171957887022754PRRHLERGRVLGRGRILLKNDPVQPP
CDH1chr1668772314ALDH3A2chr1719578870354104PRRHLERGRVLGRGRILLKNDPVQPP
CDH1chr1668772314ALDH3A2chr171957887122754PRRHLERGRVLGRGRILLKNDPVQPP
CDH1chr1668772314ALDH3A2chr1719578871354104PRRHLERGRVLGRGRILLKNDPVQPP

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Potential FusionNeoAntigen Information of CDH1-ALDH3A2 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.
CDH1-ALDH3A2_68772314_19578870.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)
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A30:08LGRGRILLK0.99180.60181019
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A30:08RVLGRGRIL0.92520.6458817
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A30:08RVLGRGRILL0.96970.6396818
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A30:08RVLGRGRILLK0.99730.6779819
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A74:03RVLGRGRILLK0.98980.5128819
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A74:09RVLGRGRILLK0.98980.5128819
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A74:11RVLGRGRILLK0.98980.5128819
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-C15:06RVLGRGRIL0.9460.8312817
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-C03:08RVLGRGRIL0.8540.9022817
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A30:01LGRGRILLK0.99320.75141019
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-C15:02RVLGRGRIL0.96240.784817
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-C15:05RVLGRGRIL0.94730.7864817
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A30:01RVLGRGRIL0.93770.7584817
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-C03:05RVLGRGRIL0.7690.7815817
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-C03:17RVLGRGRIL0.74080.8494817
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-B27:06GRVLGRGRIL0.99950.6846717
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-B27:09GRVLGRGRILL10.7559718
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-B27:06GRVLGRGRILL10.6804718
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A30:01RVLGRGRILLK0.99710.8124819
CDH1-ALDH3A2chr1668772314chr1719578870354HLA-A74:01RVLGRGRILLK0.98980.5128819

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Potential FusionNeoAntigen Information of CDH1-ALDH3A2 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.
CDH1-ALDH3A2_68772314_19578870.msa

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)
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-0437GRGRILLKNDPVQPP1126
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-0437LGRGRILLKNDPVQP1025
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-0458GRGRILLKNDPVQPP1126
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-0473GRGRILLKNDPVQPP1126
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-0804GRGRILLKNDPVQPP1126
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-1155RGRVLGRGRILLKND621
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-1170RGRVLGRGRILLKND621
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-1343RGRVLGRGRILLKND621
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-1415GRGRILLKNDPVQPP1126
CDH1-ALDH3A2chr1668772314chr1719578870354DRB1-1457GRGRILLKNDPVQPP1126

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Fusion breakpoint peptide structures of CDH1-ALDH3A2

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
7902RGRVLGRGRILLKNCDH1ALDH3A2chr1668772314chr1719578870354

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CDH1-ALDH3A2

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-B14:023BVN7902RGRVLGRGRILLKN-6.60358-6.71698
HLA-B14:023BVN7902RGRVLGRGRILLKN-1.83701-2.87231
HLA-B52:013W397902RGRVLGRGRILLKN-5.25252-5.36592
HLA-B52:013W397902RGRVLGRGRILLKN-4.16013-5.19543
HLA-A11:014UQ27902RGRVLGRGRILLKN-6.16163-7.19693
HLA-A24:025HGA7902RGRVLGRGRILLKN-8.44079-9.47609
HLA-A24:025HGA7902RGRVLGRGRILLKN-6.93479-7.04819
HLA-B44:053DX87902RGRVLGRGRILLKN-6.76785-6.88125
HLA-B44:053DX87902RGRVLGRGRILLKN-6.72058-7.75588

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Vaccine Design for the FusionNeoAntigens of CDH1-ALDH3A2

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
CDH1-ALDH3A2chr1668772314chr17195788701019LGRGRILLKTGGGCAGAGGCAGAATATTACTGAAGA
CDH1-ALDH3A2chr1668772314chr1719578870717GRVLGRGRILGCCGCGTCCTGGGCAGAGGCAGAATATTAC
CDH1-ALDH3A2chr1668772314chr1719578870718GRVLGRGRILLGCCGCGTCCTGGGCAGAGGCAGAATATTACTGA
CDH1-ALDH3A2chr1668772314chr1719578870817RVLGRGRILGCGTCCTGGGCAGAGGCAGAATATTAC
CDH1-ALDH3A2chr1668772314chr1719578870818RVLGRGRILLGCGTCCTGGGCAGAGGCAGAATATTACTGA
CDH1-ALDH3A2chr1668772314chr1719578870819RVLGRGRILLKGCGTCCTGGGCAGAGGCAGAATATTACTGAAGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CDH1-ALDH3A2chr1668772314chr17195788701025LGRGRILLKNDPVQPTGGGCAGAGGCAGAATATTACTGAAGAATGATCCTGTTCAACCTC
CDH1-ALDH3A2chr1668772314chr17195788701126GRGRILLKNDPVQPPGCAGAGGCAGAATATTACTGAAGAATGATCCTGTTCAACCTCCTA
CDH1-ALDH3A2chr1668772314chr1719578870621RGRVLGRGRILLKNDGAGGCCGCGTCCTGGGCAGAGGCAGAATATTACTGAAGAATGATC

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Information of the samples that have these potential fusion neoantigens of CDH1-ALDH3A2

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
Non-CancerCDH1-ALDH3A2chr1668772314ENST00000261769chr1719578870ENST00000176643TCGA-IN-8462-11A

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Potential target of CAR-T therapy development for CDH1-ALDH3A2

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 CDH1-ALDH3A2

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 CDH1-ALDH3A2

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