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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:ATP5I-WHSC1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ATP5I-WHSC1
FusionPDB ID: 8006
FusionGDB2.0 ID: 8006
HgeneTgene
Gene symbol

ATP5I

WHSC1

Gene ID

521

7468

Gene nameATP synthase membrane subunit enuclear receptor binding SET domain protein 2
SynonymsATP5I|ATP5KKMT3F|KMT3G|MMSET|REIIBP|TRX5|WHS|WHSC1
Cytomap

4p16.3

4p16.3

Type of geneprotein-codingprotein-coding
DescriptionATP synthase subunit e, mitochondrialATP synthase e chain, mitochondrialATP synthase, H+ transporting, mitochondrial F0 complex, subunit EATP synthase, H+ transporting, mitochondrial Fo complex subunit EATPase subunit eF1F0-ATP synthase, murine e subhistone-lysine N-methyltransferase NSD2IL5 promoter REII region-binding proteinWolf-Hirschhorn syndrome candidate 1multiple myeloma SET domain containing protein type IIInuclear SET domain-containing protein 2probable histone-lysine N-methyltransfera
Modification date2020031320200329
UniProtAcc

Q9UII2

Main function of 5'-partner protein: FUNCTION: Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of the mitochondrial matrix. Required to avoid the consumption of cellular ATP when the F(1)F(o)-ATP synthase enzyme acts as an ATP hydrolase. Indirectly acts as a regulator of heme synthesis in erythroid tissues: regulates heme synthesis by modulating the mitochondrial pH and redox potential, allowing FECH to efficiently catalyze the incorporation of iron into protoporphyrin IX to produce heme. {ECO:0000269|PubMed:12110673, ECO:0000269|PubMed:15528193, ECO:0000269|PubMed:19559621, ECO:0000269|PubMed:23135403}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000304312, ENST00000506525, 
ENST00000382888, ENST00000398261, 
ENST00000420906, ENST00000436793, 
ENST00000482415, ENST00000503128, 
ENST00000514045, ENST00000382891, 
ENST00000382892, ENST00000382895, 
ENST00000508803, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 9 X 4=32415 X 15 X 5=1125
# samples 1216
** MAII scorelog2(12/324*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1125*10)=-2.81378119121704
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ATP5I [Title/Abstract] AND WHSC1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ATP5I [Title/Abstract] AND WHSC1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ATP5I(667700)-WHSC1(1936870), # samples:1
ATP5I(667701)-WHSC1(1936871), # samples:1
Anticipated loss of major functional domain due to fusion event.ATP5I-WHSC1 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.
ATP5I-WHSC1 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.
ATP5I-WHSC1 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.
ATP5I-WHSC1 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
HgeneATP5I

GO:0042776

mitochondrial ATP synthesis coupled proton transport

12110673



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/chr4:667700/chr4:1936870)
- 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 ATP5I (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 WHSC1 (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)
ENST00000304312ATP5Ichr4667700-ENST00000508803WHSC1chr41936870+2730182102724904
ENST00000304312ATP5Ichr4667700-ENST00000382892WHSC1chr41936870+6019182102724904
ENST00000304312ATP5Ichr4667700-ENST00000382891WHSC1chr41936870+6022182102724904
ENST00000304312ATP5Ichr4667700-ENST00000382895WHSC1chr41936870+6023182102724904
ENST00000304312ATP5Ichr4667701-ENST00000508803WHSC1chr41936871+2730182102724904
ENST00000304312ATP5Ichr4667701-ENST00000382892WHSC1chr41936871+6019182102724904
ENST00000304312ATP5Ichr4667701-ENST00000382891WHSC1chr41936871+6022182102724904
ENST00000304312ATP5Ichr4667701-ENST00000382895WHSC1chr41936871+6023182102724904

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
ENST00000304312ENST00000508803ATP5Ichr4667700-WHSC1chr41936870+0.000860690.9991393
ENST00000304312ENST00000382892ATP5Ichr4667700-WHSC1chr41936870+0.0001967820.99980325
ENST00000304312ENST00000382891ATP5Ichr4667700-WHSC1chr41936870+0.0001967820.99980325
ENST00000304312ENST00000382895ATP5Ichr4667700-WHSC1chr41936870+0.0001962890.9998037
ENST00000304312ENST00000508803ATP5Ichr4667701-WHSC1chr41936871+0.000860690.9991393
ENST00000304312ENST00000382892ATP5Ichr4667701-WHSC1chr41936871+0.0001967820.99980325
ENST00000304312ENST00000382891ATP5Ichr4667701-WHSC1chr41936871+0.0001967820.99980325
ENST00000304312ENST00000382895ATP5Ichr4667701-WHSC1chr41936871+0.0001962890.9998037

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 ATP5I-WHSC1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ATP5Ichr4667700WHSC1chr4193687018258LFLGVAYGATRYSNVNGKKRNHTKRI
ATP5Ichr4667701WHSC1chr4193687118258LFLGVAYGATRYSNVNGKKRNHTKRI

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Potential FusionNeoAntigen Information of ATP5I-WHSC1 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.
ATP5I-WHSC1_667700_1936870.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)
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:05TRYSNVNGK0.99730.8664918
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:04TRYSNVNGK0.98670.7192918
ATP5I-WHSC1chr4667700chr41936870182HLA-A30:08ATRYSNVNGK0.9970.7081818
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:05ATRYSNVNGK0.91840.8706818
ATP5I-WHSC1chr4667700chr41936870182HLA-A30:08ATRYSNVNGKK0.99770.7264819
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:05GATRYSNVNGK0.9930.8415718
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:14TRYSNVNGK0.99410.7577918
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:03TRYSNVNGK0.90250.8891918
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:14TRYSNVNGKK0.99860.7986919
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:14ATRYSNVNGK0.80510.8053818
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:03ATRYSNVNGK0.51740.8949818
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:14GATRYSNVNGK0.97580.7724718
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:03GATRYSNVNGK0.86450.8685718
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:08TRYSNVNGK0.99620.7544918
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:10TRYSNVNGK0.99470.8348918
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:10TRYSNVNGKK0.99840.8653919
ATP5I-WHSC1chr4667700chr41936870182HLA-A30:01ATRYSNVNGK0.9970.8137818
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:10ATRYSNVNGK0.85390.8035818
ATP5I-WHSC1chr4667700chr41936870182HLA-A30:01ATRYSNVNGKK0.99750.8439819
ATP5I-WHSC1chr4667700chr41936870182HLA-B27:10GATRYSNVNGK0.9910.8259718

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Potential FusionNeoAntigen Information of ATP5I-WHSC1 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.
ATP5I-WHSC1_667700_1936870.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)
ATP5I-WHSC1chr4667700chr41936870182DRB1-1141YSNVNGKKRNHTKRI1126
ATP5I-WHSC1chr4667700chr41936870182DRB1-1141RYSNVNGKKRNHTKR1025
ATP5I-WHSC1chr4667700chr41936870182DRB1-1155YSNVNGKKRNHTKRI1126
ATP5I-WHSC1chr4667700chr41936870182DRB1-1155RYSNVNGKKRNHTKR1025
ATP5I-WHSC1chr4667700chr41936870182DRB5-0101ATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0101GATRYSNVNGKKRNH722
ATP5I-WHSC1chr4667700chr41936870182DRB5-0101YGATRYSNVNGKKRN621
ATP5I-WHSC1chr4667700chr41936870182DRB5-0101TRYSNVNGKKRNHTK924
ATP5I-WHSC1chr4667700chr41936870182DRB5-0102ATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0102GATRYSNVNGKKRNH722
ATP5I-WHSC1chr4667700chr41936870182DRB5-0103ATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0103GATRYSNVNGKKRNH722
ATP5I-WHSC1chr4667700chr41936870182DRB5-0103YGATRYSNVNGKKRN621
ATP5I-WHSC1chr4667700chr41936870182DRB5-0104ATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0104GATRYSNVNGKKRNH722
ATP5I-WHSC1chr4667700chr41936870182DRB5-0104YGATRYSNVNGKKRN621
ATP5I-WHSC1chr4667700chr41936870182DRB5-0104TRYSNVNGKKRNHTK924
ATP5I-WHSC1chr4667700chr41936870182DRB5-0105ATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0105GATRYSNVNGKKRNH722
ATP5I-WHSC1chr4667700chr41936870182DRB5-0105YGATRYSNVNGKKRN621
ATP5I-WHSC1chr4667700chr41936870182DRB5-0105TRYSNVNGKKRNHTK924
ATP5I-WHSC1chr4667700chr41936870182DRB5-0108NATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0108NGATRYSNVNGKKRNH722
ATP5I-WHSC1chr4667700chr41936870182DRB5-0111ATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0111GATRYSNVNGKKRNH722
ATP5I-WHSC1chr4667700chr41936870182DRB5-0111YGATRYSNVNGKKRN621
ATP5I-WHSC1chr4667700chr41936870182DRB5-0113ATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0113GATRYSNVNGKKRNH722
ATP5I-WHSC1chr4667700chr41936870182DRB5-0113YGATRYSNVNGKKRN621
ATP5I-WHSC1chr4667700chr41936870182DRB5-0113TRYSNVNGKKRNHTK924
ATP5I-WHSC1chr4667700chr41936870182DRB5-0114ATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0114GATRYSNVNGKKRNH722
ATP5I-WHSC1chr4667700chr41936870182DRB5-0114YGATRYSNVNGKKRN621
ATP5I-WHSC1chr4667700chr41936870182DRB5-0114TRYSNVNGKKRNHTK924
ATP5I-WHSC1chr4667700chr41936870182DRB5-0203ATRYSNVNGKKRNHT823
ATP5I-WHSC1chr4667700chr41936870182DRB5-0203GATRYSNVNGKKRNH722

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Fusion breakpoint peptide structures of ATP5I-WHSC1

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
10640YGATRYSNVNGKKRATP5IWHSC1chr4667700chr41936870182

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ATP5I-WHSC1

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-B14:023BVN10640YGATRYSNVNGKKR-7.15543-7.26883
HLA-B14:023BVN10640YGATRYSNVNGKKR-4.77435-5.80965
HLA-B52:013W3910640YGATRYSNVNGKKR-6.80875-6.92215
HLA-B52:013W3910640YGATRYSNVNGKKR-4.20386-5.23916
HLA-A11:014UQ210640YGATRYSNVNGKKR-7.5194-8.5547
HLA-A11:014UQ210640YGATRYSNVNGKKR-6.9601-7.0735
HLA-A24:025HGA10640YGATRYSNVNGKKR-7.52403-7.63743
HLA-A24:025HGA10640YGATRYSNVNGKKR-5.82433-6.85963
HLA-B27:056PYJ10640YGATRYSNVNGKKR-3.28285-4.31815
HLA-B44:053DX810640YGATRYSNVNGKKR-5.91172-6.94702
HLA-B44:053DX810640YGATRYSNVNGKKR-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ATP5I-WHSC1

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
ATP5I-WHSC1chr4667700chr41936870718GATRYSNVNGKACGGAGCCACGCGCTACAGTAATGTAAATGGGA
ATP5I-WHSC1chr4667700chr41936870818ATRYSNVNGKGAGCCACGCGCTACAGTAATGTAAATGGGA
ATP5I-WHSC1chr4667700chr41936870819ATRYSNVNGKKGAGCCACGCGCTACAGTAATGTAAATGGGAAAA
ATP5I-WHSC1chr4667700chr41936870918TRYSNVNGKCCACGCGCTACAGTAATGTAAATGGGA
ATP5I-WHSC1chr4667700chr41936870919TRYSNVNGKKCCACGCGCTACAGTAATGTAAATGGGAAAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ATP5I-WHSC1chr4667700chr419368701025RYSNVNGKKRNHTKRCGCGCTACAGTAATGTAAATGGGAAAAAAAGAAACCACACAAAGA
ATP5I-WHSC1chr4667700chr419368701126YSNVNGKKRNHTKRIGCTACAGTAATGTAAATGGGAAAAAAAGAAACCACACAAAGAGGA
ATP5I-WHSC1chr4667700chr41936870621YGATRYSNVNGKKRNCCTACGGAGCCACGCGCTACAGTAATGTAAATGGGAAAAAAAGAA
ATP5I-WHSC1chr4667700chr41936870722GATRYSNVNGKKRNHACGGAGCCACGCGCTACAGTAATGTAAATGGGAAAAAAAGAAACC
ATP5I-WHSC1chr4667700chr41936870823ATRYSNVNGKKRNHTGAGCCACGCGCTACAGTAATGTAAATGGGAAAAAAAGAAACCACA
ATP5I-WHSC1chr4667700chr41936870924TRYSNVNGKKRNHTKCCACGCGCTACAGTAATGTAAATGGGAAAAAAAGAAACCACACAA

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Information of the samples that have these potential fusion neoantigens of ATP5I-WHSC1

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
OVATP5I-WHSC1chr4667700ENST00000304312chr41936870ENST00000382891TCGA-24-1474

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Potential target of CAR-T therapy development for ATP5I-WHSC1

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 ATP5I-WHSC1

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 ATP5I-WHSC1

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