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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:ATP4B-CNDP2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ATP4B-CNDP2
FusionPDB ID: 7910
FusionGDB2.0 ID: 7910
HgeneTgene
Gene symbol

ATP4B

CNDP2

Gene ID

496

55748

Gene nameATPase H+/K+ transporting subunit betacarnosine dipeptidase 2
SynonymsATP6BCN2|CPGL|HEL-S-13|HsT2298|PEPA
Cytomap

13q34

18q22.3

Type of geneprotein-codingprotein-coding
Descriptionpotassium-transporting ATPase subunit betaATPase H+/K+ transporting beta subunitATPase, H+/K+ exchanging, beta polypeptideATPase, H+/K+ transporting, beta polypeptidegastric H(+)/K(+) ATPase subunit betagastric H+/K+ ATPase beta subunitgastric hydrocytosolic non-specific dipeptidaseCNDP dipeptidase 2 (metallopeptidase M20 family)carnosinase-2carnosine dipeptidase IIcytosolic nonspecific dipeptidaseepididymis secretory protein Li 13glutamate carboxypeptidase-like protein 1peptidase A
Modification date2020031320200313
UniProtAcc

P51164

Main function of 5'-partner protein: FUNCTION: Required for stabilization and maturation of the catalytic proton pump alpha subunit and may also involved in cell adhesion and establishing epithelial cell polarity. {ECO:0000269|PubMed:19694409}.

Q96KP4

Main function of 5'-partner protein: FUNCTION: Hydrolyzes a variety of dipeptides including L-carnosine but has a strong preference for Cys-Gly (PubMed:19346245). Acts as a functional tumor suppressor in gastric cancer via activation of the mitogen-activated protein kinase (MAPK) pathway. An elevated level of CNDP2 activates the p38 and JNK MAPK pathways to induce cell apoptosis, and a lower level of CNDP2 activates the ERK MAPK pathway to promote cell proliferation (PubMed:24395568). Isoform 2 may play a role as tumor suppressor in hepatocellular carcinoma (HCC) cells (PubMed:17121880). Catalyzes the production of N-lactoyl-amino acids from lactate and amino acids by reverse proteolysis (PubMed:25964343). {ECO:0000269|PubMed:17121880, ECO:0000269|PubMed:19346245, ECO:0000269|PubMed:24395568, ECO:0000269|PubMed:25964343}.
Ensembl transtripts involved in fusion geneENST idsENST00000335288, ENST00000324301, 
ENST00000580229, ENST00000324262, 
ENST00000579847, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score1 X 1 X 1=17 X 7 X 4=196
# samples 17
** MAII scorelog2(1/1*10)=3.32192809488736log2(7/196*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ATP4B [Title/Abstract] AND CNDP2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ATP4B [Title/Abstract] AND CNDP2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ATP4B(114307636)-CNDP2(72186184), # samples:1
Anticipated loss of major functional domain due to fusion event.ATP4B-CNDP2 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.
ATP4B-CNDP2 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


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/chr13:114307636/chr18:72186184)
- 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 ATP4B (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 CNDP2 (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)
ENST00000335288ATP4Bchr13114307636-ENST00000324262CNDP2chr1872186184+167539742614190
ENST00000335288ATP4Bchr13114307636-ENST00000579847CNDP2chr1872186184+167839742614190

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
ENST00000335288ENST00000324262ATP4Bchr13114307636-CNDP2chr1872186184+0.0046318660.9953681
ENST00000335288ENST00000579847ATP4Bchr13114307636-CNDP2chr1872186184+0.0047201350.9952799

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 ATP4B-CNDP2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ATP4Bchr13114307636CNDP2chr1872186184397118WADLTQTLHAFLAVFGVEPDLTREGG

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Potential FusionNeoAntigen Information of ATP4B-CNDP2 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.
ATP4B-CNDP2_114307636_72186184.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)
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:18LHAFLAVF0.99510.881715
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:01TLHAFLAVF0.99790.9448615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:25TLHAFLAVF0.98330.9547615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:02TLHAFLAVF0.97920.9623615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B46:01TLHAFLAVF0.93260.7243615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B51:01HAFLAVFGV0.72050.8048817
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B57:03QTLHAFLAVF0.99530.9928515
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A11:03AVFGVEPDLTR0.99790.54651223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A31:06AVFGVEPDLTR0.99660.68471223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A68:08AVFGVEPDLTR0.99630.56751223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A68:24AVFGVEPDLTR0.99630.52361223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A34:02AVFGVEPDLTR0.99530.55671223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A74:09AVFGVEPDLTR0.99490.80971223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A74:03AVFGVEPDLTR0.99490.80971223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A74:11AVFGVEPDLTR0.99490.80971223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A11:04AVFGVEPDLTR0.99430.52881223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A68:03AVFGVEPDLTR0.99410.51171223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A68:05AVFGVEPDLTR0.9930.51881223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A66:03AVFGVEPDLTR0.99240.62231223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A31:02AVFGVEPDLTR0.99230.79271223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A03:12AVFGVEPDLTR0.99040.58791223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:07TLHAFLAVF0.99650.8844615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:04TLHAFLAVF0.99040.9588615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:31TLHAFLAVF0.87260.9307615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:05TLHAFLAVF0.86560.9271615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B51:07HAFLAVFGV0.68040.977817
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A11:01AVFGVEPDLTR0.99860.50671223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A68:01AVFGVEPDLTR0.99630.52361223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A31:01AVFGVEPDLTR0.99570.74261223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-C15:02QTLHAFLAV0.99960.928514
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:27TLHAFLAVF0.9980.9624615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:125TLHAFLAVF0.99790.9448615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:34TLHAFLAVF0.99790.9448615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:33TLHAFLAVF0.99790.9448615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:135TLHAFLAVF0.99730.9528615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:35TLHAFLAVF0.99670.9542615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:50TLHAFLAVF0.99650.948615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A68:02QTLHAFLAV0.9930.6439514
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A68:02HAFLAVFGV0.98940.8792817
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A69:01HAFLAVFGV0.98820.7499817
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A69:01QTLHAFLAV0.98510.6003514
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:12TLHAFLAVF0.98380.9177615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:39TLHAFLAVF0.98170.9161615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B15:20TLHAFLAVF0.88210.9539615
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B51:09HAFLAVFGV0.72780.697817
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B51:13HAFLAVFGV0.71710.686817
ATP4B-CNDP2chr13114307636chr1872186184397HLA-B40:21AVFGVEPDL0.08450.60351221
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A11:02AVFGVEPDLTR0.99860.50671223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A66:02AVFGVEPDLTR0.99640.62831223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A74:01AVFGVEPDLTR0.99490.80971223
ATP4B-CNDP2chr13114307636chr1872186184397HLA-A03:02AVFGVEPDLTR0.99450.51261223

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Potential FusionNeoAntigen Information of ATP4B-CNDP2 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 ATP4B-CNDP2

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
9458TLHAFLAVFGVEPDATP4BCNDP2chr13114307636chr1872186184397

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ATP4B-CNDP2

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-B14:023BVN9458TLHAFLAVFGVEPD-7.15543-7.26883
HLA-B14:023BVN9458TLHAFLAVFGVEPD-4.77435-5.80965
HLA-B52:013W399458TLHAFLAVFGVEPD-6.80875-6.92215
HLA-B52:013W399458TLHAFLAVFGVEPD-4.20386-5.23916
HLA-A11:014UQ29458TLHAFLAVFGVEPD-7.5194-8.5547
HLA-A11:014UQ29458TLHAFLAVFGVEPD-6.9601-7.0735
HLA-A24:025HGA9458TLHAFLAVFGVEPD-7.52403-7.63743
HLA-A24:025HGA9458TLHAFLAVFGVEPD-5.82433-6.85963
HLA-B27:056PYJ9458TLHAFLAVFGVEPD-3.28285-4.31815
HLA-B44:053DX89458TLHAFLAVFGVEPD-5.91172-6.94702
HLA-B44:053DX89458TLHAFLAVFGVEPD-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ATP4B-CNDP2

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
ATP4B-CNDP2chr13114307636chr18721861841221AVFGVEPDLCAGTTTTTGGTGTTGAGCCAGACTTGA
ATP4B-CNDP2chr13114307636chr18721861841223AVFGVEPDLTRCAGTTTTTGGTGTTGAGCCAGACTTGACCAGGG
ATP4B-CNDP2chr13114307636chr1872186184514QTLHAFLAVAGACTCTCCACGCCTTCCTAGCAGTTT
ATP4B-CNDP2chr13114307636chr1872186184515QTLHAFLAVFAGACTCTCCACGCCTTCCTAGCAGTTTTTG
ATP4B-CNDP2chr13114307636chr1872186184615TLHAFLAVFCTCTCCACGCCTTCCTAGCAGTTTTTG
ATP4B-CNDP2chr13114307636chr1872186184715LHAFLAVFTCCACGCCTTCCTAGCAGTTTTTG
ATP4B-CNDP2chr13114307636chr1872186184817HAFLAVFGVACGCCTTCCTAGCAGTTTTTGGTGTTG

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 ATP4B-CNDP2

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
Non-CancerATP4B-CNDP2chr13114307636ENST00000335288chr1872186184ENST00000324262TCGA-CG-5721-11A

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Potential target of CAR-T therapy development for ATP4B-CNDP2

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
HgeneATP4Bchr13:114307636chr18:72186184ENST00000335288-3737_57118292.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

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 ATP4B-CNDP2

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 ATP4B-CNDP2

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