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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:NADK2-CDH1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NADK2-CDH1
FusionPDB ID: 57101
FusionGDB2.0 ID: 57101
HgeneTgene
Gene symbol

NADK2

CDH1

Gene ID

133686

51343

Gene nameNAD kinase 2, mitochondrialfizzy and cell division cycle 20 related 1
SynonymsC5orf33|DECRD|MNADK|NADKD1CDC20C|CDH1|FZR|FZR2|HCDH|HCDH1
Cytomap

5p13.2

19p13.3

Type of geneprotein-codingprotein-coding
DescriptionNAD kinase 2, mitochondrialNAD kinase domain-containing protein 1, mitochondrialfizzy-related protein homologCDC20 homolog 1CDC20-like 1bCDC20-like protein 1cdh1/Hct1 homologfizzy/cell division cycle 20 related 1
Modification date2020031320200313
UniProtAcc

Q4G0N4

Main function of 5'-partner protein: FUNCTION: Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH kinase activity is much weaker than the NAD(+) kinase activity and may not be relevant in vivo. {ECO:0000269|PubMed:23212377}.

Q9H159

Main function of 5'-partner protein: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
Ensembl transtripts involved in fusion geneENST idsENST00000282512, ENST00000381937, 
ENST00000397338, ENST00000506945, 
ENST00000511613, ENST00000514504, 
ENST00000562836, ENST00000261769, 
ENST00000422392, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 8 X 4=22419 X 20 X 5=1900
# samples 823
** MAII scorelog2(8/224*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(23/1900*10)=-3.04629365227394
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NADK2 [Title/Abstract] AND CDH1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NADK2 [Title/Abstract] AND CDH1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CDH1(68772314)-NADK2(36201263), # samples:2
NADK2(36207272)-CDH1(68835573), # samples:1
Anticipated loss of major functional domain due to fusion event.NADK2-CDH1 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.
NADK2-CDH1 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.
NADK2-CDH1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NADK2-CDH1 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
NADK2-CDH1 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted ORF.
CDH1-NADK2 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
CDH1-NADK2 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
CDH1-NADK2 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneNADK2

GO:0019674

NAD metabolic process

23212377

TgeneCDH1

GO:0031145

anaphase-promoting complex-dependent catabolic process

18662541|21596315

TgeneCDH1

GO:0072425

signal transduction involved in G2 DNA damage checkpoint

18662541

TgeneCDH1

GO:1904668

positive regulation of ubiquitin protein ligase activity

11459826



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/chr5:68772314/chr16:36201263)
- 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 NADK2 (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 CDH1 (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)
ENST00000282512NADK2chr536207272-ENST00000261769CDH1chr1668835573+52387035733188871
ENST00000282512NADK2chr536207272-ENST00000422392CDH1chr1668835573+30437035733005810
ENST00000506945NADK2chr536207272-ENST00000261769CDH1chr1668835573+54419068213391856
ENST00000506945NADK2chr536207272-ENST00000422392CDH1chr1668835573+32469068213208795

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
ENST00000282512ENST00000261769NADK2chr536207272-CDH1chr1668835573+0.0003917710.9996082
ENST00000282512ENST00000422392NADK2chr536207272-CDH1chr1668835573+0.0014203220.99857974
ENST00000506945ENST00000261769NADK2chr536207272-CDH1chr1668835573+0.0004604390.9995396
ENST00000506945ENST00000422392NADK2chr536207272-CDH1chr1668835573+0.0013000450.9986999

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 NADK2-CDH1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NADK2chr536207272CDH1chr166883557370343QGSICVLEQDQRPVNFEDCTGRQRTA
NADK2chr536207272CDH1chr166883557390628QGSICVLEQDQRPVNFEDCTGRQRTA

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Potential FusionNeoAntigen Information of NADK2-CDH1 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.
NADK2-CDH1_36207272_68835573.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)
NADK2-CDH1chr536207272chr1668835573703HLA-B14:02EQDQRPVNF0.92380.891716
NADK2-CDH1chr536207272chr1668835573703HLA-B14:01EQDQRPVNF0.92380.891716
NADK2-CDH1chr536207272chr1668835573703HLA-B39:01EQDQRPVNF0.9090.9203716
NADK2-CDH1chr536207272chr1668835573703HLA-B15:18EQDQRPVNF0.8830.7967716
NADK2-CDH1chr536207272chr1668835573703HLA-B39:13EQDQRPVNF0.82280.9467716
NADK2-CDH1chr536207272chr1668835573703HLA-B38:02EQDQRPVNF0.80790.948716
NADK2-CDH1chr536207272chr1668835573703HLA-B38:01EQDQRPVNF0.79720.9445716
NADK2-CDH1chr536207272chr1668835573703HLA-B15:10EQDQRPVNF0.69650.573716
NADK2-CDH1chr536207272chr1668835573703HLA-B13:01EQDQRPVNF0.60750.8894716
NADK2-CDH1chr536207272chr1668835573703HLA-B15:37EQDQRPVNF0.52280.6893716
NADK2-CDH1chr536207272chr1668835573703HLA-B44:03LEQDQRPVNF0.9990.9646616
NADK2-CDH1chr536207272chr1668835573703HLA-C05:09EQDQRPVNF0.99950.9316716
NADK2-CDH1chr536207272chr1668835573703HLA-C04:07EQDQRPVNF0.99940.8982716
NADK2-CDH1chr536207272chr1668835573703HLA-C04:10EQDQRPVNF0.99940.8764716
NADK2-CDH1chr536207272chr1668835573703HLA-C08:15EQDQRPVNF0.99750.968716
NADK2-CDH1chr536207272chr1668835573703HLA-B39:09EQDQRPVNF0.93810.8259716
NADK2-CDH1chr536207272chr1668835573703HLA-B39:12EQDQRPVNF0.87920.9228716
NADK2-CDH1chr536207272chr1668835573703HLA-B39:08EQDQRPVNF0.85350.8922716
NADK2-CDH1chr536207272chr1668835573703HLA-B15:31EQDQRPVNF0.83310.8987716
NADK2-CDH1chr536207272chr1668835573703HLA-B15:21EQDQRPVNF0.80780.9396716
NADK2-CDH1chr536207272chr1668835573703HLA-C04:14EQDQRPVNF0.67220.9046716
NADK2-CDH1chr536207272chr1668835573703HLA-B14:03EQDQRPVNF0.61760.8875716
NADK2-CDH1chr536207272chr1668835573703HLA-B44:10LEQDQRPVNF0.97820.5692616
NADK2-CDH1chr536207272chr1668835573703HLA-C05:01EQDQRPVNF0.99950.9316716
NADK2-CDH1chr536207272chr1668835573703HLA-C04:03EQDQRPVNF0.99940.9155716
NADK2-CDH1chr536207272chr1668835573703HLA-C04:01EQDQRPVNF0.99940.8982716
NADK2-CDH1chr536207272chr1668835573703HLA-C18:01EQDQRPVNF0.99860.8914716
NADK2-CDH1chr536207272chr1668835573703HLA-C08:02EQDQRPVNF0.99750.968716
NADK2-CDH1chr536207272chr1668835573703HLA-B39:02EQDQRPVNF0.9310.9478716
NADK2-CDH1chr536207272chr1668835573703HLA-C07:04EQDQRPVNF0.92360.9311716
NADK2-CDH1chr536207272chr1668835573703HLA-B39:31EQDQRPVNF0.92070.9185716
NADK2-CDH1chr536207272chr1668835573703HLA-B18:04EQDQRPVNF0.85760.9547716
NADK2-CDH1chr536207272chr1668835573703HLA-B48:02EQDQRPVNF0.83010.9232716
NADK2-CDH1chr536207272chr1668835573703HLA-C04:04EQDQRPVNF0.81920.9432716
NADK2-CDH1chr536207272chr1668835573703HLA-B39:11EQDQRPVNF0.80320.8136716
NADK2-CDH1chr536207272chr1668835573703HLA-B35:20EQDQRPVNF0.79940.9501716
NADK2-CDH1chr536207272chr1668835573703HLA-B38:05EQDQRPVNF0.79720.9445716
NADK2-CDH1chr536207272chr1668835573703HLA-B18:07EQDQRPVNF0.78730.9294716
NADK2-CDH1chr536207272chr1668835573703HLA-B15:12EQDQRPVNF0.76850.8491716
NADK2-CDH1chr536207272chr1668835573703HLA-B18:03EQDQRPVNF0.74880.944716
NADK2-CDH1chr536207272chr1668835573703HLA-B18:08EQDQRPVNF0.74090.944716
NADK2-CDH1chr536207272chr1668835573703HLA-B15:13EQDQRPVNF0.54930.6551716
NADK2-CDH1chr536207272chr1668835573703HLA-B08:12EQDQRPVNF0.49520.5566716
NADK2-CDH1chr536207272chr1668835573703HLA-B15:53EQDQRPVNF0.45510.8539716
NADK2-CDH1chr536207272chr1668835573703HLA-B15:09EQDQRPVNF0.43580.671716
NADK2-CDH1chr536207272chr1668835573703HLA-B44:13LEQDQRPVNF0.9990.9646616
NADK2-CDH1chr536207272chr1668835573703HLA-B44:26LEQDQRPVNF0.9990.9646616
NADK2-CDH1chr536207272chr1668835573703HLA-B44:07LEQDQRPVNF0.9990.9646616
NADK2-CDH1chr536207272chr1668835573703HLA-B15:53LEQDQRPVNF0.99450.8543616
NADK2-CDH1chr536207272chr1668835573703HLA-B18:11LEQDQRPVNF0.97990.9616

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Potential FusionNeoAntigen Information of NADK2-CDH1 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 NADK2-CDH1

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
4923LEQDQRPVNFEDCTNADK2CDH1chr536207272chr1668835573703

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NADK2-CDH1

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-B14:023BVN4923LEQDQRPVNFEDCT-7.9962-8.1096
HLA-B14:023BVN4923LEQDQRPVNFEDCT-5.70842-6.74372
HLA-B52:013W394923LEQDQRPVNFEDCT-6.83737-6.95077
HLA-B52:013W394923LEQDQRPVNFEDCT-4.4836-5.5189
HLA-A11:014UQ24923LEQDQRPVNFEDCT-10.0067-10.1201
HLA-A11:014UQ24923LEQDQRPVNFEDCT-9.03915-10.0745
HLA-A24:025HGA4923LEQDQRPVNFEDCT-6.56204-6.67544
HLA-A24:025HGA4923LEQDQRPVNFEDCT-5.42271-6.45801
HLA-B44:053DX84923LEQDQRPVNFEDCT-7.85648-8.89178
HLA-B44:053DX84923LEQDQRPVNFEDCT-5.3978-5.5112
HLA-A02:016TDR4923LEQDQRPVNFEDCT-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NADK2-CDH1

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
NADK2-CDH1chr536207272chr1668835573616LEQDQRPVNFTGGAACAGGATCAAAGGCCTGTGAATTTTG
NADK2-CDH1chr536207272chr1668835573716EQDQRPVNFAACAGGATCAAAGGCCTGTGAATTTTG

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 NADK2-CDH1

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
BRCANADK2-CDH1chr536207272ENST00000282512chr1668835573ENST00000261769TCGA-A2-A4RW-01A

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Potential target of CAR-T therapy development for NADK2-CDH1

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
TgeneCDH1chr5:36207272chr16:68835573ENST00000261769116710_7300883.0TransmembraneHelical

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 NADK2-CDH1

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 NADK2-CDH1

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