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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:NOLC1-IYD

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NOLC1-IYD
FusionPDB ID: 59580
FusionGDB2.0 ID: 59580
HgeneTgene
Gene symbol

NOLC1

IYD

Gene ID

9221

389434

Gene namenucleolar and coiled-body phosphoprotein 1iodotyrosine deiodinase
SynonymsNOPP130|NOPP140|NS5ATP13|P130|Srp40C6orf71|DEHAL1|IYD-1|TDH4
Cytomap

10q24.32

6q25.1

Type of geneprotein-codingprotein-coding
Descriptionnucleolar and coiled-body phosphoprotein 1140 kDa nucleolar phosphoproteinHCV NS5A trans-regulated protein 13HCV NS5A-transactivated protein 13hepatitis C virus NS5A-transactivated protein 13nucleolar 130 kDa proteinnucleolar and coiled-body phosphpiodotyrosine deiodinase 1iodotyrosine dehalogenase 1
Modification date2020031320200313
UniProtAcc

Q14978

Main function of 5'-partner protein: FUNCTION: Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:10567578, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with TCOF1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in nucleologenesis, possibly by playing a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus (PubMed:9016786). It has intrinsic GTPase and ATPase activities (PubMed:9016786). {ECO:0000269|PubMed:10567578, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:9016786}.

Q6PHW0

Main function of 5'-partner protein: FUNCTION: Catalyzes the oxidative NADPH-dependent deiodination of monoiodotyrosine (L-MIT) or diiodotyrosine (L-DIT) (PubMed:15289438, PubMed:25395621, PubMed:18434651). Acts during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways (PubMed:18434651). Acts more efficiently on monoiodotyrosine than on diiodotyrosine (PubMed:15289438). {ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651, ECO:0000269|PubMed:25395621}.
Ensembl transtripts involved in fusion geneENST idsENST00000477977, ENST00000405356, 
ENST00000488254, ENST00000603742, 
ENST00000605788, 
ENST00000229447, 
ENST00000344419, ENST00000392255, 
ENST00000392256, ENST00000425615, 
ENST00000500320, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 7 X 2=984 X 4 X 4=64
# samples 75
** MAII scorelog2(7/98*10)=-0.485426827170242
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/64*10)=-0.356143810225275
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NOLC1 [Title/Abstract] AND IYD [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NOLC1 [Title/Abstract] AND IYD [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NOLC1(103920547)-IYD(150713589), # samples:1
Anticipated loss of major functional domain due to fusion event.NOLC1-IYD 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.
NOLC1-IYD 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
TgeneIYD

GO:0006570

tyrosine metabolic process

25395621

TgeneIYD

GO:0042403

thyroid hormone metabolic process

25395621

TgeneIYD

GO:0055114

oxidation-reduction process

25395621



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/chr10:103920547/chr6:150713589)
- 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 NOLC1 (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 IYD (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)
ENST00000605788NOLC1chr10103920547-ENST00000229447IYDchr6150713589-853116371871644485
ENST00000605788NOLC1chr10103920547-ENST00000344419IYDchr6150713589-976016371871644485
ENST00000605788NOLC1chr10103920547-ENST00000392256IYDchr6150713589-196116371871644485
ENST00000605788NOLC1chr10103920547-ENST00000392255IYDchr6150713589-230316371871644485
ENST00000605788NOLC1chr10103920547-ENST00000500320IYDchr6150713589-328116371871644485
ENST00000605788NOLC1chr10103920547-ENST00000425615IYDchr6150713589-198416371871644485
ENST00000405356NOLC1chr10103920547-ENST00000229447IYDchr6150713589-856116671871674495
ENST00000405356NOLC1chr10103920547-ENST00000344419IYDchr6150713589-979016671871674495
ENST00000405356NOLC1chr10103920547-ENST00000392256IYDchr6150713589-199116671871674495
ENST00000405356NOLC1chr10103920547-ENST00000392255IYDchr6150713589-233316671871674495
ENST00000405356NOLC1chr10103920547-ENST00000500320IYDchr6150713589-331116671871674495
ENST00000405356NOLC1chr10103920547-ENST00000425615IYDchr6150713589-201416671871674495
ENST00000603742NOLC1chr10103920547-ENST00000229447IYDchr6150713589-815412601971267356
ENST00000603742NOLC1chr10103920547-ENST00000344419IYDchr6150713589-938312601971267356
ENST00000603742NOLC1chr10103920547-ENST00000392256IYDchr6150713589-158412601971267356
ENST00000603742NOLC1chr10103920547-ENST00000392255IYDchr6150713589-192612601971267356
ENST00000603742NOLC1chr10103920547-ENST00000500320IYDchr6150713589-290412601971267356
ENST00000603742NOLC1chr10103920547-ENST00000425615IYDchr6150713589-160712601971267356
ENST00000488254NOLC1chr10103920547-ENST00000229447IYDchr6150713589-8306141271419470
ENST00000488254NOLC1chr10103920547-ENST00000344419IYDchr6150713589-9535141271419470
ENST00000488254NOLC1chr10103920547-ENST00000392256IYDchr6150713589-1736141271419470
ENST00000488254NOLC1chr10103920547-ENST00000392255IYDchr6150713589-2078141271419470
ENST00000488254NOLC1chr10103920547-ENST00000500320IYDchr6150713589-3056141271419470
ENST00000488254NOLC1chr10103920547-ENST00000425615IYDchr6150713589-1759141271419470

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
ENST00000605788ENST00000229447NOLC1chr10103920547-IYDchr6150713589-0.0003529610.999647
ENST00000605788ENST00000344419NOLC1chr10103920547-IYDchr6150713589-0.0002815960.99971837
ENST00000605788ENST00000392256NOLC1chr10103920547-IYDchr6150713589-0.007729830.9922701
ENST00000605788ENST00000392255NOLC1chr10103920547-IYDchr6150713589-0.0069629550.99303705
ENST00000605788ENST00000500320NOLC1chr10103920547-IYDchr6150713589-0.0016397760.9983602
ENST00000605788ENST00000425615NOLC1chr10103920547-IYDchr6150713589-0.0076463410.9923537
ENST00000405356ENST00000229447NOLC1chr10103920547-IYDchr6150713589-0.0004606940.9995394
ENST00000405356ENST00000344419NOLC1chr10103920547-IYDchr6150713589-0.0003677540.99963224
ENST00000405356ENST00000392256NOLC1chr10103920547-IYDchr6150713589-0.0097625340.99023753
ENST00000405356ENST00000392255NOLC1chr10103920547-IYDchr6150713589-0.0084096720.9915903
ENST00000405356ENST00000500320NOLC1chr10103920547-IYDchr6150713589-0.0020280730.99797195
ENST00000405356ENST00000425615NOLC1chr10103920547-IYDchr6150713589-0.0097539070.99024606
ENST00000603742ENST00000229447NOLC1chr10103920547-IYDchr6150713589-0.0004316380.9995684
ENST00000603742ENST00000344419NOLC1chr10103920547-IYDchr6150713589-0.000267250.9997328
ENST00000603742ENST00000392256NOLC1chr10103920547-IYDchr6150713589-0.0020628220.9979372
ENST00000603742ENST00000392255NOLC1chr10103920547-IYDchr6150713589-0.0024156330.99758434
ENST00000603742ENST00000500320NOLC1chr10103920547-IYDchr6150713589-0.0010527070.9989473
ENST00000603742ENST00000425615NOLC1chr10103920547-IYDchr6150713589-0.0021734160.9978265
ENST00000488254ENST00000229447NOLC1chr10103920547-IYDchr6150713589-0.0004971470.9995029
ENST00000488254ENST00000344419NOLC1chr10103920547-IYDchr6150713589-0.0003933250.99960667
ENST00000488254ENST00000392256NOLC1chr10103920547-IYDchr6150713589-0.014248550.98575145
ENST00000488254ENST00000392255NOLC1chr10103920547-IYDchr6150713589-0.0126927770.9873072
ENST00000488254ENST00000500320NOLC1chr10103920547-IYDchr6150713589-0.0027801870.9972198
ENST00000488254ENST00000425615NOLC1chr10103920547-IYDchr6150713589-0.0139563210.9860437

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 NOLC1-IYD

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

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Potential FusionNeoAntigen Information of NOLC1-IYD 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 NOLC1-IYD 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 NOLC1-IYD

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 NOLC1-IYD

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 NOLC1-IYD

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 NOLC1-IYD

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 NOLC1-IYD

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
TgeneIYDchr10:103920547chr6:150713589ENST0000022944706215_2350294.0TransmembraneHelical
TgeneIYDchr10:103920547chr6:150713589ENST0000034441905215_2350290.0TransmembraneHelical
TgeneIYDchr10:103920547chr6:150713589ENST0000039225606215_2350180.66666666666666TransmembraneHelical

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 NOLC1-IYD

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 NOLC1-IYD

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