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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:ETHE1-CADM4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ETHE1-CADM4
FusionPDB ID: 27645
FusionGDB2.0 ID: 27645
HgeneTgene
Gene symbol

ETHE1

CADM4

Gene ID

23474

199731

Gene nameETHE1 persulfide dioxygenasecell adhesion molecule 4
SynonymsHSCO|YF13H12IGSF4C|NECL4|Necl-4|TSLL2|synCAM4
Cytomap

19q13.31

19q13.31

Type of geneprotein-codingprotein-coding
Descriptionpersulfide dioxygenase ETHE1, mitochondrialethylmalonic encephalopathy 1hepatoma subtracted clone one proteinprotein ETHE1, mitochondrialsulfur dioxygenase ETHE1cell adhesion molecule 4TSLC1-like 2TSLC1-like protein 2immunoglobulin superfamily member 4Cnectin-like 4nectin-like protein 4
Modification date2020031320200313
UniProtAcc

O95571

Main function of 5'-partner protein: FUNCTION: Sulfur dioxygenase that plays an essential role in hydrogen sulfide catabolism in the mitochondrial matrix. Hydrogen sulfide (H(2)S) is first oxidized by SQRDL, giving rise to cysteine persulfide residues. ETHE1 consumes molecular oxygen to catalyze the oxidation of the persulfide, once it has been transferred to a thiophilic acceptor, such as glutathione (R-SSH). Plays an important role in metabolic homeostasis in mitochondria by metabolizing hydrogen sulfide and preventing the accumulation of supraphysiological H(2)S levels that have toxic effects, due to the inhibition of cytochrome c oxidase. First described as a protein that can shuttle between the nucleus and the cytoplasm and suppress p53-induced apoptosis by sequestering the transcription factor RELA/NFKB3 in the cytoplasm and preventing its accumulation in the nucleus (PubMed:12398897). {ECO:0000269|PubMed:12398897, ECO:0000269|PubMed:14732903, ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459}.

Q8NFZ8

Main function of 5'-partner protein: FUNCTION: Involved in the cell-cell adhesion. Has calcium- and magnesium-independent cell-cell adhesion activity. May have tumor-suppressor activity. {ECO:0000269|PubMed:16261159}.
Ensembl transtripts involved in fusion geneENST idsENST00000292147, ENST00000600651, 
ENST00000593506, ENST00000222374, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 7 X 8=5601 X 1 X 1=1
# samples 111
** MAII scorelog2(11/560*10)=-2.34792330342031
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: ETHE1 [Title/Abstract] AND CADM4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ETHE1 [Title/Abstract] AND CADM4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ETHE1(44015589)-CADM4(44131942), # samples:1
Anticipated loss of major functional domain due to fusion event.ETHE1-CADM4 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.
ETHE1-CADM4 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
HgeneETHE1

GO:0006749

glutathione metabolic process

23144459

HgeneETHE1

GO:0070813

hydrogen sulfide metabolic process

23144459



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/chr19:44015589/chr19:44131942)
- 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 ETHE1 (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 CADM4 (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)
ENST00000292147ETHE1chr1944015589-ENST00000222374CADM4chr1944131942-2637572671674535
ENST00000600651ETHE1chr1944015589-ENST00000222374CADM4chr1944131942-2594529241631535

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
ENST00000292147ENST00000222374ETHE1chr1944015589-CADM4chr1944131942-0.0015173390.99848264
ENST00000600651ENST00000222374ETHE1chr1944015589-CADM4chr1944131942-0.0014082570.9985917

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 ETHE1-CADM4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ETHE1chr1944015589CADM4chr1944131942529168LLIRGCGRTDFQQGAGQEVQTENVTV
ETHE1chr1944015589CADM4chr1944131942572168LLIRGCGRTDFQQGAGQEVQTENVTV

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Potential FusionNeoAntigen Information of ETHE1-CADM4 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.
ETHE1-CADM4_44015589_44131942.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)
ETHE1-CADM4chr1944015589chr1944131942572HLA-A02:21FQQGAGQEV0.90850.79291019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B48:01FQQGAGQEV0.85120.8461019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B13:02FQQGAGQEV0.71110.97941019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B39:01FQQGAGQEV0.64360.98531019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B39:13FQQGAGQEV0.61950.99311019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B13:01FQQGAGQEV0.53160.99531019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B15:10FQQGAGQEV0.34730.83181019
ETHE1-CADM4chr1944015589chr1944131942572HLA-A02:19FQQGAGQEV0.22730.59531019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B27:14GRTDFQQGA0.99670.6832615
ETHE1-CADM4chr1944015589chr1944131942572HLA-B73:01GRTDFQQGA0.98090.9479615
ETHE1-CADM4chr1944015589chr1944131942572HLA-A02:05FQQGAGQEV0.95720.67871019
ETHE1-CADM4chr1944015589chr1944131942572HLA-C08:13FQQGAGQEV0.8630.99281019
ETHE1-CADM4chr1944015589chr1944131942572HLA-C08:04FQQGAGQEV0.8630.99281019
ETHE1-CADM4chr1944015589chr1944131942572HLA-C02:06FQQGAGQEV0.79870.97711019
ETHE1-CADM4chr1944015589chr1944131942572HLA-C08:03FQQGAGQEV0.74450.99661019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B39:08FQQGAGQEV0.71160.96511019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B39:05FQQGAGQEV0.56810.98381019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B48:03FQQGAGQEV0.50630.84941019
ETHE1-CADM4chr1944015589chr1944131942572HLA-A02:14FQQGAGQEV0.90870.74531019
ETHE1-CADM4chr1944015589chr1944131942572HLA-A02:06FQQGAGQEV0.90850.79291019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B15:73FQQGAGQEV0.89540.9941019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B15:30FQQGAGQEV0.79090.99061019
ETHE1-CADM4chr1944015589chr1944131942572HLA-C08:01FQQGAGQEV0.74450.99661019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B39:11FQQGAGQEV0.66530.93781019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B39:02FQQGAGQEV0.66180.9931019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B40:12FQQGAGQEV0.50630.84941019
ETHE1-CADM4chr1944015589chr1944131942572HLA-C07:04FQQGAGQEV0.44540.93521019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B40:21FQQGAGQEV0.43530.86991019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B40:49FQQGAGQEV0.38560.84431019
ETHE1-CADM4chr1944015589chr1944131942572HLA-B15:09FQQGAGQEV0.18940.97671019

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Potential FusionNeoAntigen Information of ETHE1-CADM4 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.
ETHE1-CADM4_44015589_44131942.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)
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0109RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0109GRTDFQQGAGQEVQT621
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0111RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0113RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0115RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0117RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0121RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0901RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0901GRTDFQQGAGQEVQT621
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0902RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0903RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0904RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0904GRTDFQQGAGQEVQT621
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0904CGRTDFQQGAGQEVQ520
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0905RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0905GRTDFQQGAGQEVQT621
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0905CGRTDFQQGAGQEVQ520
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0907RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0907GRTDFQQGAGQEVQT621
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0907CGRTDFQQGAGQEVQ520
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0909RTDFQQGAGQEVQTE722
ETHE1-CADM4chr1944015589chr1944131942572DRB1-0909GRTDFQQGAGQEVQT621

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Fusion breakpoint peptide structures of ETHE1-CADM4

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
3098GRTDFQQGAGQEVQETHE1CADM4chr1944015589chr1944131942572

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ETHE1-CADM4

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-B14:023BVN3098GRTDFQQGAGQEVQ-7.17232-7.28572
HLA-B14:023BVN3098GRTDFQQGAGQEVQ-4.95948-5.99478
HLA-B52:013W393098GRTDFQQGAGQEVQ-6.80683-6.92023
HLA-B52:013W393098GRTDFQQGAGQEVQ-3.90062-4.93592
HLA-A11:014UQ23098GRTDFQQGAGQEVQ1000110000
HLA-A24:025HGA3098GRTDFQQGAGQEVQ-8.77961-8.89301
HLA-A24:025HGA3098GRTDFQQGAGQEVQ-5.66496-6.70026
HLA-B44:053DX83098GRTDFQQGAGQEVQ-5.65551-5.76891
HLA-B44:053DX83098GRTDFQQGAGQEVQ-3.88952-4.92482
HLA-A02:016TDR3098GRTDFQQGAGQEVQ-4.65662-5.69192

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Vaccine Design for the FusionNeoAntigens of ETHE1-CADM4

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
ETHE1-CADM4chr1944015589chr19441319421019FQQGAGQEVTCCAGCAAGGGGCAGGACAGGAAGTAC
ETHE1-CADM4chr1944015589chr1944131942615GRTDFQQGAGGCGGACAGACTTCCAGCAAGGGGCAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ETHE1-CADM4chr1944015589chr1944131942520CGRTDFQQGAGQEVQGTGGGCGGACAGACTTCCAGCAAGGGGCAGGACAGGAAGTACAGA
ETHE1-CADM4chr1944015589chr1944131942621GRTDFQQGAGQEVQTGGCGGACAGACTTCCAGCAAGGGGCAGGACAGGAAGTACAGACAG
ETHE1-CADM4chr1944015589chr1944131942722RTDFQQGAGQEVQTEGGACAGACTTCCAGCAAGGGGCAGGACAGGAAGTACAGACAGAGA

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Information of the samples that have these potential fusion neoantigens of ETHE1-CADM4

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
LUSCETHE1-CADM4chr1944015589ENST00000292147chr1944131942ENST00000222374TCGA-66-2758-01A

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Potential target of CAR-T therapy development for ETHE1-CADM4

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
TgeneCADM4chr19:44015589chr19:44131942ENST0000022237409325_3450389.0TransmembraneHelical

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 ETHE1-CADM4

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 ETHE1-CADM4

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