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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:NIPBL-MYO10

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NIPBL-MYO10
FusionPDB ID: 59206
FusionGDB2.0 ID: 59206
HgeneTgene
Gene symbol

NIPBL

MYO10

Gene ID

25836

4651

Gene nameNIPBL cohesin loading factormyosin X
SynonymsCDLS|CDLS1|IDN3|IDN3-B|Scc2-
Cytomap

5p13.2

5p15.1

Type of geneprotein-codingprotein-coding
Descriptionnipped-B-like proteinNipped-B homologSCC2 homologdelanginsister chromatid cohesion 2 homologunconventional myosin-Xunconventional myosin-10unconventionnal myosin-X
Modification date2020031320200313
UniProtAcc

Q6KC79

Main function of 5'-partner protein: FUNCTION: Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}.

Q9HD67

Main function of 5'-partner protein: FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. MYO10 binds to actin filaments and actin bundles and functions as plus end-directed motor. The tail domain binds to membranous compartments containing phosphatidylinositol 3,4,5-trisphosphate or integrins, and mediates cargo transport along actin filaments. Regulates cell shape, cell spreading and cell adhesion. Stimulates the formation and elongation of filopodia. May play a role in neurite outgrowth and axon guidance. In hippocampal neurons it induces the formation of dendritic filopodia by trafficking the actin-remodeling protein VASP to the tips of filopodia, where it promotes actin elongation. Plays a role in formation of the podosome belt in osteoclasts. {ECO:0000269|PubMed:16894163, ECO:0000269|PubMed:18570893}.; FUNCTION: [Isoform Headless]: Functions as a dominant-negative regulator of isoform 1, suppressing its filopodia-inducing and axon outgrowth-promoting activities. In hippocampal neurons, it increases VASP retention in spine heads to induce spine formation and spine head expansion (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000282516, ENST00000448238, 
ENST00000504430, 
ENST00000274203, 
ENST00000427430, ENST00000505695, 
ENST00000512061, ENST00000515803, 
ENST00000507288, ENST00000513610, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score26 X 13 X 16=54089 X 11 X 4=396
# samples 4311
** MAII scorelog2(43/5408*10)=-3.65268658669272
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/396*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NIPBL [Title/Abstract] AND MYO10 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NIPBL [Title/Abstract] AND MYO10 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NIPBL(37010327)-MYO10(16877816), # samples:3
Anticipated loss of major functional domain due to fusion event.NIPBL-MYO10 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.
NIPBL-MYO10 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
HgeneNIPBL

GO:0000122

negative regulation of transcription by RNA polymerase II

18854353

HgeneNIPBL

GO:0031065

positive regulation of histone deacetylation

18854353

HgeneNIPBL

GO:0045892

negative regulation of transcription, DNA-templated

18854353

HgeneNIPBL

GO:0071921

cohesin loading

22628566



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/chr5:37010327/chr5:16877816)
- 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 NIPBL (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 MYO10 (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)
ENST00000282516NIPBLchr537010327+ENST00000513610MYO10chr516877816-126215059499112143571
ENST00000282516NIPBLchr537010327+ENST00000507288MYO10chr516877816-6264505949953311610
ENST00000448238NIPBLchr537010327+ENST00000513610MYO10chr516877816-125905028468111833571
ENST00000448238NIPBLchr537010327+ENST00000507288MYO10chr516877816-6233502846853001610

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
ENST00000282516ENST00000513610NIPBLchr537010327+MYO10chr516877816-0.0008924940.99910754
ENST00000282516ENST00000507288NIPBLchr537010327+MYO10chr516877816-0.0006203970.99937963
ENST00000448238ENST00000513610NIPBLchr537010327+MYO10chr516877816-0.0008764460.9991235
ENST00000448238ENST00000507288NIPBLchr537010327+MYO10chr516877816-0.0006159350.99938405

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 NIPBL-MYO10

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NIPBLchr537010327MYO10chr51687781650281520EKDSNAEEDSNKKGTRVWLRENGQHF
NIPBLchr537010327MYO10chr51687781650591520EKDSNAEEDSNKKGTRVWLRENGQHF

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Potential FusionNeoAntigen Information of NIPBL-MYO10 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.
NIPBL-MYO10_37010327_16877816.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)
NIPBL-MYO10chr537010327chr5168778165059HLA-B58:06SNKKGTRVW0.92510.7712918

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Potential FusionNeoAntigen Information of NIPBL-MYO10 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 NIPBL-MYO10

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
1638EEDSNKKGTRVWLRNIPBLMYO10chr537010327chr5168778165059

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NIPBL-MYO10

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-B14:023BVN1638EEDSNKKGTRVWLR-7.9962-8.1096
HLA-B14:023BVN1638EEDSNKKGTRVWLR-5.70842-6.74372
HLA-B52:013W391638EEDSNKKGTRVWLR-6.83737-6.95077
HLA-B52:013W391638EEDSNKKGTRVWLR-4.4836-5.5189
HLA-A11:014UQ21638EEDSNKKGTRVWLR-10.0067-10.1201
HLA-A11:014UQ21638EEDSNKKGTRVWLR-9.03915-10.0745
HLA-A24:025HGA1638EEDSNKKGTRVWLR-6.56204-6.67544
HLA-A24:025HGA1638EEDSNKKGTRVWLR-5.42271-6.45801
HLA-B44:053DX81638EEDSNKKGTRVWLR-7.85648-8.89178
HLA-B44:053DX81638EEDSNKKGTRVWLR-5.3978-5.5112
HLA-A02:016TDR1638EEDSNKKGTRVWLR-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NIPBL-MYO10

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
NIPBL-MYO10chr537010327chr516877816918SNKKGTRVWTCAAATAAAAAAGGAACACGGGTCTGG

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 NIPBL-MYO10

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
LUADNIPBL-MYO10chr537010327ENST00000282516chr516877816ENST00000507288TCGA-05-4426-01A

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Potential target of CAR-T therapy development for NIPBL-MYO10

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 NIPBL-MYO10

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 NIPBL-MYO10

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