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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:NDUFC1-PCDH10

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NDUFC1-PCDH10
FusionPDB ID: 58209
FusionGDB2.0 ID: 58209
HgeneTgene
Gene symbol

NDUFC1

PCDH10

Gene ID

4717

57575

Gene nameNADH:ubiquinone oxidoreductase subunit C1protocadherin 10
SynonymsKFYIOL-PCDH|PCDH19
Cytomap

4q31.1

4q28.3

Type of geneprotein-codingprotein-coding
DescriptionNADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrialCI-KFYINADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 1, 6kDaNADH-ubiquinone oxidoreductase KFYI subunitcomplex I KFYI subunitcomplex I-KFYIprotocadherin-10
Modification date2020032020200313
UniProtAcc

O43677

Main function of 5'-partner protein: FUNCTION: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000265500, ENST00000394223, 
ENST00000394228, ENST00000505036, 
ENST00000507764, ENST00000539002, 
ENST00000539387, ENST00000544855, 
ENST00000264360, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 2=181 X 1 X 1=1
# samples 31
** MAII scorelog2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: NDUFC1 [Title/Abstract] AND PCDH10 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NDUFC1 [Title/Abstract] AND PCDH10 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NDUFC1(140216886)-PCDH10(134111296), # samples:1
Anticipated loss of major functional domain due to fusion event.NDUFC1-PCDH10 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.
NDUFC1-PCDH10 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.
NDUFC1-PCDH10 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NDUFC1-PCDH10 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
NDUFC1-PCDH10 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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


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/chr4:140216886/chr4:134111296)
- 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 NDUFC1 (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 PCDH10 (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)
ENST00000544855NDUFC1chr4140216886-ENST00000264360PCDH10chr4134111296+53678977081028106

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
ENST00000544855ENST00000264360NDUFC1chr4140216886-PCDH10chr4134111296+0.55761510.44238484

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 NDUFC1-PCDH10

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NDUFC1chr4140216886PCDH10chr413411129689763FPGCWPPPGSRAAHGKGYASQFYRTY

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Potential FusionNeoAntigen Information of NDUFC1-PCDH10 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.
NDUFC1-PCDH10_140216886_134111296.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)
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B27:05SRAAHGKGY0.99570.791918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B27:04SRAAHGKGY0.9950.7197918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B15:03SRAAHGKGY0.22380.7265918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B15:18SRAAHGKGY0.20510.6145918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B15:18AHGKGYASQF0.96740.68911222
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B38:02AHGKGYASQF0.94050.93951222
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B38:01AHGKGYASQF0.93050.9531222
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B27:03SRAAHGKGY0.94160.8003918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:27SRAAHGKGY0.90590.9029918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:05SRAAHGKGY0.84150.8155918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:19SRAAHGKGY0.78060.5514918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:80SRAAHGKGY0.74340.8657918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:67SRAAHGKGY0.74340.8657918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:10SRAAHGKGY0.7280.9205918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:46SRAAHGKGY0.70780.7812918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C12:16SRAAHGKGY0.0120.9323918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B27:08SRAAHGKGY0.99540.6621918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B27:10SRAAHGKGY0.99450.8381918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:17SRAAHGKGY0.86320.8912918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:02SRAAHGKGY0.74340.8657918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C07:22SRAAHGKGY0.67150.5013918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C06:08SRAAHGKGY0.40180.9862918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C06:06SRAAHGKGY0.03180.9809918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B15:54SRAAHGKGY0.01850.8158918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B15:68SRAAHGKGY0.00850.5671918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C06:17SRAAHGKGY0.00130.9875918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-C06:02SRAAHGKGY0.00130.9875918
NDUFC1-PCDH10chr4140216886chr4134111296897HLA-B38:05AHGKGYASQF0.93050.9531222

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Potential FusionNeoAntigen Information of NDUFC1-PCDH10 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 NDUFC1-PCDH10

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
6860PPGSRAAHGKGYASNDUFC1PCDH10chr4140216886chr4134111296897

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NDUFC1-PCDH10

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-B14:023BVN6860PPGSRAAHGKGYAS-5.16857-5.28197
HLA-B14:023BVN6860PPGSRAAHGKGYAS-4.21097-5.24627
HLA-B52:013W396860PPGSRAAHGKGYAS-4.32839-4.44179
HLA-B52:013W396860PPGSRAAHGKGYAS-4.10962-5.14492
HLA-A24:025HGA6860PPGSRAAHGKGYAS-6.03661-6.15001
HLA-A24:025HGA6860PPGSRAAHGKGYAS-5.99594-7.03124
HLA-B44:053DX86860PPGSRAAHGKGYAS-6.27779-6.39119
HLA-B44:053DX86860PPGSRAAHGKGYAS-4.76488-5.80018

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Vaccine Design for the FusionNeoAntigens of NDUFC1-PCDH10

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
NDUFC1-PCDH10chr4140216886chr41341112961222AHGKGYASQFGCCCACGGAAAAGGATATGCTAGTCAATTC
NDUFC1-PCDH10chr4140216886chr4134111296918SRAAHGKGYTCCCGAGCGGCCCACGGAAAAGGATAT

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 NDUFC1-PCDH10

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
GBMNDUFC1-PCDH10chr4140216886ENST00000544855chr4134111296ENST00000264360TCGA-06-0129-01A

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Potential target of CAR-T therapy development for NDUFC1-PCDH10

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
HgeneNDUFC1chr4:140216886chr4:134111296ENST00000505036-2541_5922-1.3333333333333333TransmembraneHelical
HgeneNDUFC1chr4:140216886chr4:134111296ENST00000539002-2541_5922-117.0TransmembraneHelical
HgeneNDUFC1chr4:140216886chr4:134111296ENST00000544855-3641_5922-60.333333333333336TransmembraneHelical

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 NDUFC1-PCDH10

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 NDUFC1-PCDH10

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