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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:NME2-ACBD4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NME2-ACBD4
FusionPDB ID: 59416
FusionGDB2.0 ID: 59416
HgeneTgene
Gene symbol

NME2

ACBD4

Gene ID

4831

79777

Gene nameNME/NM23 nucleoside diphosphate kinase 2acyl-CoA binding domain containing 4
SynonymsNDKB|NDPK-B|NDPKB|NM23-H2|NM23B|PUFHMFT0700
Cytomap

17q21.33

17q21.31

Type of geneprotein-codingprotein-coding
Descriptionnucleoside diphosphate kinase BHEL-S-155anNDP kinase Bc-myc purine-binding transcription factor PUFc-myc transcription factorepididymis secretory sperm binding protein Li 155anhistidine protein kinase NDKBnon-metastatic cells 2, protein (NM23) expracyl-CoA-binding domain-containing protein 4acyl-Coenzyme A binding domain containing 4
Modification date2020032720200320
UniProtAcc

O60361

Main function of 5'-partner protein: FUNCTION: Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). {ECO:0000250}.

Q8NC06

Main function of 5'-partner protein: FUNCTION: Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters.
Ensembl transtripts involved in fusion geneENST idsENST00000376392, ENST00000393193, 
ENST00000555572, 
ENST00000321854, 
ENST00000376955, ENST00000591136, 
ENST00000592162, ENST00000398322, 
ENST00000431281, ENST00000586346, 
ENST00000591859, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 4=1442 X 2 X 2=8
# samples 62
** MAII scorelog2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: NME2 [Title/Abstract] AND ACBD4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NME2 [Title/Abstract] AND ACBD4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NME2(49244317)-ACBD4(43216388), # samples:2
Anticipated loss of major functional domain due to fusion event.NME2-ACBD4 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.
NME2-ACBD4 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.
NME2-ACBD4 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.
NME2-ACBD4 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.
NME2-ACBD4 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
NME2-ACBD4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NME2-ACBD4 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
NME2-ACBD4 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
HgeneNME2

GO:0006165

nucleoside diphosphate phosphorylation

25679041

HgeneNME2

GO:0007229

integrin-mediated signaling pathway

11919189

HgeneNME2

GO:0009142

nucleoside triphosphate biosynthetic process

1851158|25679041

HgeneNME2

GO:0045893

positive regulation of transcription, DNA-templated

8392752

HgeneNME2

GO:0045944

positive regulation of transcription by RNA polymerase II

15703214



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/chr17:49244317/chr17:43216388)
- 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 NME2 (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 ACBD4 (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)
ENST00000393193NME2chr1749244317+ENST00000431281ACBD4chr1743216388+141854838886282
ENST00000393193NME2chr1749244317+ENST00000591859ACBD4chr1743216388+142254838886282
ENST00000393193NME2chr1749244317+ENST00000586346ACBD4chr1743216388+109654838886282
ENST00000376392NME2chr1749244317+ENST00000431281ACBD4chr1743216388+140453424872282
ENST00000376392NME2chr1749244317+ENST00000591859ACBD4chr1743216388+140853424872282
ENST00000376392NME2chr1749244317+ENST00000586346ACBD4chr1743216388+108253424872282
ENST00000555572NME2chr1749244317+ENST00000431281ACBD4chr1743216388+15927221761060294
ENST00000555572NME2chr1749244317+ENST00000591859ACBD4chr1743216388+15967221761060294
ENST00000555572NME2chr1749244317+ENST00000586346ACBD4chr1743216388+12707221761060294

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
ENST00000393193ENST00000431281NME2chr1749244317+ACBD4chr1743216388+0.31645150.68354845
ENST00000393193ENST00000591859NME2chr1749244317+ACBD4chr1743216388+0.309814130.6901859
ENST00000393193ENST00000586346NME2chr1749244317+ACBD4chr1743216388+0.211469670.78853035
ENST00000376392ENST00000431281NME2chr1749244317+ACBD4chr1743216388+0.323275120.6767249
ENST00000376392ENST00000591859NME2chr1749244317+ACBD4chr1743216388+0.31948420.6805158
ENST00000376392ENST00000586346NME2chr1749244317+ACBD4chr1743216388+0.218256740.7817433
ENST00000555572ENST00000431281NME2chr1749244317+ACBD4chr1743216388+0.37498530.6250147
ENST00000555572ENST00000591859NME2chr1749244317+ACBD4chr1743216388+0.37144870.6285513
ENST00000555572ENST00000586346NME2chr1749244317+ACBD4chr1743216388+0.332068620.66793144

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 NME2-ACBD4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NME2chr1749244317ACBD4chr1743216388534170QKGFRLVAMKFLRRGCGAARRGPRSW
NME2chr1749244317ACBD4chr1743216388548170QKGFRLVAMKFLRRGCGAARRGPRSW
NME2chr1749244317ACBD4chr1743216388722182QKGFRLVAMKFLRRGCGAARRGPRSW

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Potential FusionNeoAntigen Information of NME2-ACBD4 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.
NME2-ACBD4_49244317_43216388.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)
NME2-ACBD4chr1749244317chr1743216388534HLA-A74:11LVAMKFLRR0.95810.6548514
NME2-ACBD4chr1749244317chr1743216388534HLA-A74:09LVAMKFLRR0.95810.6548514
NME2-ACBD4chr1749244317chr1743216388534HLA-A74:03LVAMKFLRR0.95810.6548514
NME2-ACBD4chr1749244317chr1743216388534HLA-A31:02LVAMKFLRR0.86820.6003514
NME2-ACBD4chr1749244317chr1743216388534HLA-A74:11RLVAMKFLRR0.99170.7323414
NME2-ACBD4chr1749244317chr1743216388534HLA-A74:03RLVAMKFLRR0.99170.7323414
NME2-ACBD4chr1749244317chr1743216388534HLA-A74:09RLVAMKFLRR0.99170.7323414
NME2-ACBD4chr1749244317chr1743216388534HLA-A31:01LVAMKFLRR0.96620.5776514
NME2-ACBD4chr1749244317chr1743216388534HLA-A31:01RLVAMKFLRR0.99220.7134414
NME2-ACBD4chr1749244317chr1743216388534HLA-A74:01LVAMKFLRR0.95810.6548514
NME2-ACBD4chr1749244317chr1743216388534HLA-A74:01RLVAMKFLRR0.99170.7323414

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Potential FusionNeoAntigen Information of NME2-ACBD4 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 NME2-ACBD4

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
9799VAMKFLRRGCGAARNME2ACBD4chr1749244317chr1743216388534

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NME2-ACBD4

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-B14:023BVN9799VAMKFLRRGCGAAR-7.9962-8.1096
HLA-B14:023BVN9799VAMKFLRRGCGAAR-5.70842-6.74372
HLA-B52:013W399799VAMKFLRRGCGAAR-6.83737-6.95077
HLA-B52:013W399799VAMKFLRRGCGAAR-4.4836-5.5189
HLA-A11:014UQ29799VAMKFLRRGCGAAR-10.0067-10.1201
HLA-A11:014UQ29799VAMKFLRRGCGAAR-9.03915-10.0745
HLA-A24:025HGA9799VAMKFLRRGCGAAR-6.56204-6.67544
HLA-A24:025HGA9799VAMKFLRRGCGAAR-5.42271-6.45801
HLA-B44:053DX89799VAMKFLRRGCGAAR-7.85648-8.89178
HLA-B44:053DX89799VAMKFLRRGCGAAR-5.3978-5.5112
HLA-A02:016TDR9799VAMKFLRRGCGAAR-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NME2-ACBD4

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
NME2-ACBD4chr1749244317chr1743216388414RLVAMKFLRRCGCCTCGTGGCCATGAAGTTCCTCCGGAGG
NME2-ACBD4chr1749244317chr1743216388514LVAMKFLRRCTCGTGGCCATGAAGTTCCTCCGGAGG

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 NME2-ACBD4

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
LUADNME2-ACBD4chr1749244317ENST00000376392chr1743216388ENST00000431281TCGA-44-3396-01A

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Potential target of CAR-T therapy development for NME2-ACBD4

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 NME2-ACBD4

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 NME2-ACBD4

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