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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:KDM4B-MPND

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KDM4B-MPND
FusionPDB ID: 41808
FusionGDB2.0 ID: 41808
HgeneTgene
Gene symbol

KDM4B

MPND

Gene ID

23030

84954

Gene namelysine demethylase 4BMPN domain containing
SynonymsJMJD2B|TDRD14B-
Cytomap

19p13.3

19p13.3

Type of geneprotein-codingprotein-coding
Descriptionlysine-specific demethylase 4BjmjC domain-containing histone demethylation protein 3Bjumonji domain containing 2Bjumonji domain-containing protein 2Blysine (K)-specific demethylase 4Btudor domain containing 14BMPN domain-containing protein
Modification date2020031320200313
UniProtAcc

O94953

Main function of 5'-partner protein: FUNCTION: Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}.

Q8N594

Main function of 5'-partner protein: FUNCTION: Probable protease (By similarity). Acts as a sensor of N(6)-methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA, leading to its degradation (PubMed:30982744). {ECO:0000250|UniProtKB:Q5VVJ2, ECO:0000269|PubMed:30982744}.
Ensembl transtripts involved in fusion geneENST idsENST00000159111, ENST00000381759, 
ENST00000536461, ENST00000592175, 
ENST00000262966, ENST00000359935, 
ENST00000599840, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score30 X 16 X 14=67203 X 2 X 2=12
# samples 383
** MAII scorelog2(38/6720*10)=-4.14438990933518
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/12*10)=1.32192809488736
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: KDM4B [Title/Abstract] AND MPND [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KDM4B [Title/Abstract] AND MPND [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KDM4B(5082515)-MPND(4345742), # samples:3
Anticipated loss of major functional domain due to fusion event.KDM4B-MPND 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.
KDM4B-MPND 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.
KDM4B-MPND 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.
KDM4B-MPND 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
HgeneKDM4B

GO:0033169

histone H3-K9 demethylation

21914792

HgeneKDM4B

GO:0070544

histone H3-K36 demethylation

21914792



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/chr19:5082515/chr19:4345742)
- 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 KDM4B (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 MPND (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)
ENST00000159111KDM4Bchr195082515+ENST00000262966MPNDchr194345742+234211362182257679
ENST00000159111KDM4Bchr195082515+ENST00000359935MPNDchr194345742+227711362182197659
ENST00000159111KDM4Bchr195082515+ENST00000599840MPNDchr194345742+241811362182347709
ENST00000381759KDM4Bchr195082515+ENST00000262966MPNDchr194345742+233111252072246679
ENST00000381759KDM4Bchr195082515+ENST00000359935MPNDchr194345742+226611252072186659
ENST00000381759KDM4Bchr195082515+ENST00000599840MPNDchr194345742+240711252072336709
ENST00000536461KDM4Bchr195082515+ENST00000262966MPNDchr194345742+2164958402079679
ENST00000536461KDM4Bchr195082515+ENST00000359935MPNDchr194345742+2099958402019659
ENST00000536461KDM4Bchr195082515+ENST00000599840MPNDchr194345742+2240958402169709

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
ENST00000159111ENST00000262966KDM4Bchr195082515+MPNDchr194345742+0.0065882510.9934117
ENST00000159111ENST00000359935KDM4Bchr195082515+MPNDchr194345742+0.0054756120.99452436
ENST00000159111ENST00000599840KDM4Bchr195082515+MPNDchr194345742+0.0043137870.9956863
ENST00000381759ENST00000262966KDM4Bchr195082515+MPNDchr194345742+0.0063091250.99369085
ENST00000381759ENST00000359935KDM4Bchr195082515+MPNDchr194345742+0.0052185410.99478143
ENST00000381759ENST00000599840KDM4Bchr195082515+MPNDchr194345742+0.0040977450.99590224
ENST00000536461ENST00000262966KDM4Bchr195082515+MPNDchr194345742+0.0063179890.993682
ENST00000536461ENST00000359935KDM4Bchr195082515+MPNDchr194345742+0.0051373180.99486274
ENST00000536461ENST00000599840KDM4Bchr195082515+MPNDchr194345742+0.0040643550.9959357

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 KDM4B-MPND

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KDM4Bchr195082515MPNDchr1943457421125305ATLRWIDYGKVATQGKKFLGDLQPDG
KDM4Bchr195082515MPNDchr1943457421136305ATLRWIDYGKVATQGKKFLGDLQPDG
KDM4Bchr195082515MPNDchr194345742958305ATLRWIDYGKVATQGKKFLGDLQPDG

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Potential FusionNeoAntigen Information of KDM4B-MPND 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.
KDM4B-MPND_5082515_4345742.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)
KDM4B-MPNDchr195082515chr1943457421136HLA-B15:17KVATQGKKF0.96030.8905918
KDM4B-MPNDchr195082515chr1943457421136HLA-B58:02KVATQGKKF0.94080.8845918
KDM4B-MPNDchr195082515chr1943457421136HLA-A32:13KVATQGKKF0.79270.9503918
KDM4B-MPNDchr195082515chr1943457421136HLA-C03:07VATQGKKFL0.98350.98261019
KDM4B-MPNDchr195082515chr1943457421136HLA-C03:19VATQGKKFL0.98280.991019
KDM4B-MPNDchr195082515chr1943457421136HLA-C03:08VATQGKKFL0.96880.93521019
KDM4B-MPNDchr195082515chr1943457421136HLA-C15:06VATQGKKFL0.9410.94661019
KDM4B-MPNDchr195082515chr1943457421136HLA-C15:04KVATQGKKF0.82680.8589918
KDM4B-MPNDchr195082515chr1943457421136HLA-C06:03VATQGKKFL0.39810.99181019
KDM4B-MPNDchr195082515chr1943457421136HLA-C12:12VATQGKKFL0.38680.9611019
KDM4B-MPNDchr195082515chr1943457421136HLA-C12:04VATQGKKFL0.38160.9891019
KDM4B-MPNDchr195082515chr1943457421136HLA-C16:01VATQGKKF0.97960.97481018
KDM4B-MPNDchr195082515chr1943457421136HLA-C03:05VATQGKKFL0.97520.92691019
KDM4B-MPNDchr195082515chr1943457421136HLA-C03:17VATQGKKFL0.97350.97621019
KDM4B-MPNDchr195082515chr1943457421136HLA-C03:03VATQGKKFL0.97340.98971019
KDM4B-MPNDchr195082515chr1943457421136HLA-C03:04VATQGKKFL0.97340.98971019
KDM4B-MPNDchr195082515chr1943457421136HLA-B58:06KVATQGKKF0.96470.8172918
KDM4B-MPNDchr195082515chr1943457421136HLA-B15:135KVATQGKKF0.96130.872918
KDM4B-MPNDchr195082515chr1943457421136HLA-A32:01KVATQGKKF0.95120.9449918
KDM4B-MPNDchr195082515chr1943457421136HLA-B15:24KVATQGKKF0.9420.9006918
KDM4B-MPNDchr195082515chr1943457421136HLA-C15:09KVATQGKKF0.82680.8589918
KDM4B-MPNDchr195082515chr1943457421136HLA-C03:06VATQGKKFL0.61010.99071019
KDM4B-MPNDchr195082515chr1943457421136HLA-C16:01VATQGKKFL0.45680.98141019
KDM4B-MPNDchr195082515chr1943457421136HLA-C16:04VATQGKKFL0.44750.98171019
KDM4B-MPNDchr195082515chr1943457421136HLA-C12:03VATQGKKFL0.40220.97991019
KDM4B-MPNDchr195082515chr1943457421136HLA-C16:02VATQGKKFL0.390.99191019
KDM4B-MPNDchr195082515chr1943457421136HLA-C02:10KVATQGKKF0.29250.9711918
KDM4B-MPNDchr195082515chr1943457421136HLA-C02:02KVATQGKKF0.29250.9711918
KDM4B-MPNDchr195082515chr1943457421136HLA-B07:13VATQGKKFL0.28220.86341019

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Potential FusionNeoAntigen Information of KDM4B-MPND 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 KDM4B-MPND

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
1490DYGKVATQGKKFLGKDM4BMPNDchr195082515chr1943457421136

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KDM4B-MPND

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-B53:011A1O1490DYGKVATQGKKFLG1.029880.916483
HLA-B53:011A1O1490DYGKVATQGKKFLG2.144891.10959
HLA-B51:011E281490DYGKVATQGKKFLG-1.32428-2.35958
HLA-B51:011E281490DYGKVATQGKKFLG1.28081.1674
HLA-B57:032BVO1490DYGKVATQGKKFLG1.083530.970133
HLA-B14:023BVN1490DYGKVATQGKKFLG-3.16289-3.27629
HLA-B14:023BVN1490DYGKVATQGKKFLG-0.0811614-1.11646
HLA-B52:013W391490DYGKVATQGKKFLG-2.4019-2.5153
HLA-B52:013W391490DYGKVATQGKKFLG-0.200478-1.23578
HLA-B18:014JQV1490DYGKVATQGKKFLG-1.43426-1.54766
HLA-B18:014JQV1490DYGKVATQGKKFLG0.0242455-1.01105
HLA-A11:014UQ21490DYGKVATQGKKFLG-4.22168-5.25698
HLA-A11:014UQ21490DYGKVATQGKKFLG-3.91734-4.03074
HLA-A24:025HGA1490DYGKVATQGKKFLG-3.0088-3.1222
HLA-A24:025HGA1490DYGKVATQGKKFLG-0.761617-1.79692
HLA-B57:015VUD1490DYGKVATQGKKFLG0.658078-0.377222
HLA-C08:026JTP1490DYGKVATQGKKFLG-1.64096-1.75436
HLA-C08:026JTP1490DYGKVATQGKKFLG1.710160.674858
HLA-B37:016MT41490DYGKVATQGKKFLG-0.248758-1.28406
HLA-B27:056PYJ1490DYGKVATQGKKFLG-2.79481-2.90821
HLA-B27:056PYJ1490DYGKVATQGKKFLG0.129514-0.905786
HLA-B27:036PZ51490DYGKVATQGKKFLG-1.7736-1.887
HLA-B27:036PZ51490DYGKVATQGKKFLG-0.0872939-1.12259
HLA-B44:053DX81490DYGKVATQGKKFLG-1.66951-1.78291
HLA-B44:053DX81490DYGKVATQGKKFLG0.0086321-1.02667
HLA-B07:025EO01490DYGKVATQGKKFLG1.05330.018001
HLA-B07:025EO01490DYGKVATQGKKFLG1.608751.49535
HLA-A02:016TDR1490DYGKVATQGKKFLG-2.62934-2.74274
HLA-A02:016TDR1490DYGKVATQGKKFLG0.532159-0.503141

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Vaccine Design for the FusionNeoAntigens of KDM4B-MPND

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
KDM4B-MPNDchr195082515chr1943457421018VATQGKKFGCCACTCAGGGGAAGAAGTTCCTG
KDM4B-MPNDchr195082515chr1943457421019VATQGKKFLGCCACTCAGGGGAAGAAGTTCCTGGGC
KDM4B-MPNDchr195082515chr194345742918KVATQGKKFGTGGCCACTCAGGGGAAGAAGTTCCTG

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 KDM4B-MPND

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
OVKDM4B-MPNDchr195082515ENST00000159111chr194345742ENST00000262966TCGA-10-0926-01A

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Potential target of CAR-T therapy development for KDM4B-MPND

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 KDM4B-MPND

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 KDM4B-MPND

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