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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:SSH2-ANO1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SSH2-ANO1
FusionPDB ID: 86763
FusionGDB2.0 ID: 86763
HgeneTgene
Gene symbol

SSH2

ANO1

Gene ID

85464

55107

Gene nameslingshot protein phosphatase 2anoctamin 1
SynonymsSSH-2|SSH-2LDOG1|ORAOV2|TAOS2|TMEM16A
Cytomap

17q11.2

11q13.3

Type of geneprotein-codingprotein-coding
Descriptionprotein phosphatase Slingshot homolog 2SSH-like protein 2anoctamin-1Ca2+-activated Cl- channelanoctamin 1, calcium activated chloride channelcalcium activated chloride channeldiscovered on gastrointestinal stromal tumors protein 1oral cancer overexpressed 2transmembrane protein 16A (eight membrane-spannin
Modification date2020031320200313
UniProtAcc.

Q9NW15

Main function of 5'-partner protein: FUNCTION: Does not exhibit calcium-activated chloride channel (CaCC) activity. Can inhibit the activity of ANO1. {ECO:0000269|PubMed:20056604, ECO:0000269|PubMed:22946059}.
Ensembl transtripts involved in fusion geneENST idsENST00000269033, ENST00000540801, 
ENST00000579954, ENST00000582084, 
ENST00000590153, ENST00000324677, 
ENST00000525494, ENST00000316296, 
ENST00000355303, ENST00000398543, 
ENST00000530676, ENST00000531349, 
ENST00000538023, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score39 X 23 X 10=897019 X 28 X 10=5320
# samples 4836
** MAII scorelog2(48/8970*10)=-4.22400167419811
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(36/5320*10)=-3.88535743405888
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SSH2 [Title/Abstract] AND ANO1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SSH2 [Title/Abstract] AND ANO1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SSH2(28256956)-ANO1(69957813), # samples:2
Anticipated loss of major functional domain due to fusion event.SSH2-ANO1 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.
SSH2-ANO1 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.
SSH2-ANO1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
SSH2-ANO1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
SSH2-ANO1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneANO1

GO:0006812

cation transport

22946059



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/chr17:28256956/chr11:69957813)
- 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 SSH2 (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 ANO1 (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)
ENST00000269033SSH2chr1728256956-ENST00000355303ANO1chr1169962564+38452151522320722
ENST00000269033SSH2chr1728256956-ENST00000398543ANO1chr1169962564+37542151522230692
ENST00000269033SSH2chr1728256956-ENST00000538023ANO1chr1169962564+38442151522320722
ENST00000269033SSH2chr1728256956-ENST00000316296ANO1chr1169962564+14572151521372406
ENST00000269033SSH2chr1728256956-ENST00000530676ANO1chr1169962564+25082151522230692
ENST00000269033SSH2chr1728256956-ENST00000531349ANO1chr1169962564+34912151522242696
ENST00000540801SSH2chr1728256956-ENST00000355303ANO1chr1169962564+3786156932261722
ENST00000540801SSH2chr1728256956-ENST00000398543ANO1chr1169962564+3695156932171692
ENST00000540801SSH2chr1728256956-ENST00000538023ANO1chr1169962564+3785156932261722
ENST00000540801SSH2chr1728256956-ENST00000316296ANO1chr1169962564+1398156931313406
ENST00000540801SSH2chr1728256956-ENST00000530676ANO1chr1169962564+2449156932171692
ENST00000540801SSH2chr1728256956-ENST00000531349ANO1chr1169962564+3432156932183696
ENST00000590153SSH2chr1728256956-ENST00000355303ANO1chr1169962564+39212912282396722
ENST00000590153SSH2chr1728256956-ENST00000398543ANO1chr1169962564+38302912282306692
ENST00000590153SSH2chr1728256956-ENST00000538023ANO1chr1169962564+39202912282396722
ENST00000590153SSH2chr1728256956-ENST00000316296ANO1chr1169962564+15332912281448406
ENST00000590153SSH2chr1728256956-ENST00000530676ANO1chr1169962564+25842912282306692
ENST00000590153SSH2chr1728256956-ENST00000531349ANO1chr1169962564+35672912282318696
ENST00000579954SSH2chr1728256956-ENST00000355303ANO1chr1169962564+3755125622230722
ENST00000579954SSH2chr1728256956-ENST00000398543ANO1chr1169962564+3664125622140692
ENST00000579954SSH2chr1728256956-ENST00000538023ANO1chr1169962564+3754125622230722
ENST00000579954SSH2chr1728256956-ENST00000316296ANO1chr1169962564+1367125621282406
ENST00000579954SSH2chr1728256956-ENST00000530676ANO1chr1169962564+2418125622140692
ENST00000579954SSH2chr1728256956-ENST00000531349ANO1chr1169962564+3401125622152696

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
ENST00000269033ENST00000355303SSH2chr1728256956-ANO1chr1169962564+0.0027923050.9972077
ENST00000269033ENST00000398543SSH2chr1728256956-ANO1chr1169962564+0.0026192780.9973807
ENST00000269033ENST00000538023SSH2chr1728256956-ANO1chr1169962564+0.0026747210.9973253
ENST00000269033ENST00000316296SSH2chr1728256956-ANO1chr1169962564+0.0086333920.99136657
ENST00000269033ENST00000530676SSH2chr1728256956-ANO1chr1169962564+0.0092725410.9907274
ENST00000269033ENST00000531349SSH2chr1728256956-ANO1chr1169962564+0.0044909590.995509
ENST00000540801ENST00000355303SSH2chr1728256956-ANO1chr1169962564+0.002782830.9972172
ENST00000540801ENST00000398543SSH2chr1728256956-ANO1chr1169962564+0.0025881350.9974119
ENST00000540801ENST00000538023SSH2chr1728256956-ANO1chr1169962564+0.0026617910.99733824
ENST00000540801ENST00000316296SSH2chr1728256956-ANO1chr1169962564+0.0084423850.9915576
ENST00000540801ENST00000530676SSH2chr1728256956-ANO1chr1169962564+0.0095632650.99043673
ENST00000540801ENST00000531349SSH2chr1728256956-ANO1chr1169962564+0.0045548940.99544513
ENST00000590153ENST00000355303SSH2chr1728256956-ANO1chr1169962564+0.0027680460.9972319
ENST00000590153ENST00000398543SSH2chr1728256956-ANO1chr1169962564+0.0026082710.9973917
ENST00000590153ENST00000538023SSH2chr1728256956-ANO1chr1169962564+0.0026578480.99734217
ENST00000590153ENST00000316296SSH2chr1728256956-ANO1chr1169962564+0.0085408830.99145913
ENST00000590153ENST00000530676SSH2chr1728256956-ANO1chr1169962564+0.0091723650.9908276
ENST00000590153ENST00000531349SSH2chr1728256956-ANO1chr1169962564+0.0044895270.99551046
ENST00000579954ENST00000355303SSH2chr1728256956-ANO1chr1169962564+0.0028008840.99719906
ENST00000579954ENST00000398543SSH2chr1728256956-ANO1chr1169962564+0.0025672190.99743277
ENST00000579954ENST00000538023SSH2chr1728256956-ANO1chr1169962564+0.0026789940.99732107
ENST00000579954ENST00000316296SSH2chr1728256956-ANO1chr1169962564+0.0084538380.9915461
ENST00000579954ENST00000530676SSH2chr1728256956-ANO1chr1169962564+0.0097251730.9902748
ENST00000579954ENST00000531349SSH2chr1728256956-ANO1chr1169962564+0.0046017970.9953982

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 SSH2-ANO1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SSH2chr1728256956ANO1chr116996256412521SPTPSTTSSPCASGDYNGENVEFNDR
SSH2chr1728256956ANO1chr116996256415621SPTPSTTSSPCASGDYNGENVEFNDR
SSH2chr1728256956ANO1chr116996256421521SPTPSTTSSPCASGDYNGENVEFNDR
SSH2chr1728256956ANO1chr116996256429121SPTPSTTSSPCASGDYNGENVEFNDR

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Potential FusionNeoAntigen Information of SSH2-ANO1 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.

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)

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Potential FusionNeoAntigen Information of SSH2-ANO1 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 SSH2-ANO1

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SSH2-ANO1

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

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Vaccine Design for the FusionNeoAntigens of SSH2-ANO1

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

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 SSH2-ANO1

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

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Potential target of CAR-T therapy development for SSH2-ANO1

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
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617334_3540643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617407_4270643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617520_5400643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617569_5890643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617608_6280643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617658_6780643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617726_7460643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617747_7670643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617785_8050643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000316296617893_9130643.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626334_3540987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626407_4270987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626520_5400987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626569_5890987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626608_6280987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626658_6780987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626726_7460987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626747_7670987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626785_8050987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000355303626893_9130987.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624334_3540841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624407_4270841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624520_5400841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624569_5890841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624608_6280841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624658_6780841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624726_7460841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624747_7670841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624785_8050841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000398543624893_9130841.0TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625334_3540819.3333333333334TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625407_4270819.3333333333334TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625520_5400819.3333333333334TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625569_5890819.3333333333334TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625608_6280819.3333333333334TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625658_6780819.3333333333334TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625726_7460819.3333333333334TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625747_7670819.3333333333334TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625785_8050819.3333333333334TransmembraneHelical
TgeneANO1chr17:28256956chr11:69962564ENST00000530676625893_9130819.3333333333334TransmembraneHelical

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 SSH2-ANO1

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 SSH2-ANO1

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