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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-KLF11

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KDM4B-KLF11
FusionPDB ID: 41806
FusionGDB2.0 ID: 41806
HgeneTgene
Gene symbol

KDM4B

KLF11

Gene ID

23030

8462

Gene namelysine demethylase 4BKruppel like factor 11
SynonymsJMJD2B|TDRD14BFKLF|FKLF1|MODY7|TIEG2|Tieg3
Cytomap

19p13.3

2p25.1

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 14BKrueppel-like factor 11TGFB-inducible early growth response protein 2TIEG-2transforming growth factor-beta-inducible early growth response protein 2
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}.

O14901

Main function of 5'-partner protein: FUNCTION: Transcription factor (PubMed:9748269, PubMed:10207080). Activates the epsilon- and gamma-globin gene promoters and, to a much lower degree, the beta-globin gene and represses promoters containing SP1-like binding inhibiting cell growth (PubMed:9748269, PubMed:10207080, PubMed:16131492). Represses transcription of SMAD7 which enhances TGF-beta signaling (By similarity). Induces apoptosis (By similarity). {ECO:0000250|UniProtKB:Q8K1S5, ECO:0000269|PubMed:10207080, ECO:0000269|PubMed:16131492}.
Ensembl transtripts involved in fusion geneENST idsENST00000159111, ENST00000381759, 
ENST00000536461, ENST00000592175, 
ENST00000535335, ENST00000540845, 
ENST00000305883, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score30 X 16 X 14=67202 X 2 X 2=8
# samples 382
** MAII scorelog2(38/6720*10)=-4.14438990933518
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: KDM4B [Title/Abstract] AND KLF11 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KDM4B [Title/Abstract] AND KLF11 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KDM4B(5041262)-KLF11(10186277), # samples:1
Anticipated loss of major functional domain due to fusion event.KDM4B-KLF11 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-KLF11 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-KLF11 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-KLF11 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

TgeneKLF11

GO:0000083

regulation of transcription involved in G1/S transition of mitotic cell cycle

21171965

TgeneKLF11

GO:0000122

negative regulation of transcription by RNA polymerase II

21171965

TgeneKLF11

GO:0008285

negative regulation of cell proliferation

21171965

TgeneKLF11

GO:0043065

positive regulation of apoptotic process

21171965



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/chr19:5041262/chr2:10186277)
- 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 KLF11 (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)
ENST00000159111KDM4Bchr195041262+ENST00000305883KLF11chr210186277+44766502182146642
ENST00000381759KDM4Bchr195041262+ENST00000305883KLF11chr210186277+44656392072135642
ENST00000536461KDM4Bchr195041262+ENST00000305883KLF11chr210186277+4298472401968642

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
ENST00000159111ENST00000305883KDM4Bchr195041262+KLF11chr210186277+0.000507870.99949217
ENST00000381759ENST00000305883KDM4Bchr195041262+KLF11chr210186277+0.0004909530.9995091
ENST00000536461ENST00000305883KDM4Bchr195041262+KLF11chr210186277+0.0004300220.99956995

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-KLF11

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KDM4Bchr195041262KLF11chr210186277472144IYGADISGSLYDDVDIMDICESILER
KDM4Bchr195041262KLF11chr210186277639144IYGADISGSLYDDVDIMDICESILER
KDM4Bchr195041262KLF11chr210186277650144IYGADISGSLYDDVDIMDICESILER

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Potential FusionNeoAntigen Information of KDM4B-KLF11 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-KLF11_5041262_10186277.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-KLF11chr195041262chr210186277650HLA-A02:21SLYDDVDIM0.96570.5431817
KDM4B-KLF11chr195041262chr210186277650HLA-C04:07LYDDVDIM0.99990.5207917
KDM4B-KLF11chr195041262chr210186277650HLA-C04:10LYDDVDIM0.99990.5011917
KDM4B-KLF11chr195041262chr210186277650HLA-C04:14LYDDVDIM0.97630.6101917
KDM4B-KLF11chr195041262chr210186277650HLA-C04:10LYDDVDIMDI0.99740.5295919
KDM4B-KLF11chr195041262chr210186277650HLA-C04:07LYDDVDIMDI0.99710.5367919
KDM4B-KLF11chr195041262chr210186277650HLA-C04:01LYDDVDIM0.99990.5207917
KDM4B-KLF11chr195041262chr210186277650HLA-C18:01LYDDVDIM0.99990.5338917
KDM4B-KLF11chr195041262chr210186277650HLA-C04:04LYDDVDIM0.98490.772917
KDM4B-KLF11chr195041262chr210186277650HLA-A02:06SLYDDVDIM0.96570.5431817
KDM4B-KLF11chr195041262chr210186277650HLA-B15:73SLYDDVDIM0.84460.5901817
KDM4B-KLF11chr195041262chr210186277650HLA-B15:30SLYDDVDIM0.79060.5704817
KDM4B-KLF11chr195041262chr210186277650HLA-C04:01LYDDVDIMDI0.99710.5367919
KDM4B-KLF11chr195041262chr210186277650HLA-C18:01LYDDVDIMDI0.99460.5653919

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Potential FusionNeoAntigen Information of KDM4B-KLF11 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-KLF11

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
8609SGSLYDDVDIMDICKDM4BKLF11chr195041262chr210186277650

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KDM4B-KLF11

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-B14:023BVN8609SGSLYDDVDIMDIC-7.9962-8.1096
HLA-B14:023BVN8609SGSLYDDVDIMDIC-5.70842-6.74372
HLA-B52:013W398609SGSLYDDVDIMDIC-6.83737-6.95077
HLA-B52:013W398609SGSLYDDVDIMDIC-4.4836-5.5189
HLA-A11:014UQ28609SGSLYDDVDIMDIC-10.0067-10.1201
HLA-A11:014UQ28609SGSLYDDVDIMDIC-9.03915-10.0745
HLA-A24:025HGA8609SGSLYDDVDIMDIC-6.56204-6.67544
HLA-A24:025HGA8609SGSLYDDVDIMDIC-5.42271-6.45801
HLA-B44:053DX88609SGSLYDDVDIMDIC-7.85648-8.89178
HLA-B44:053DX88609SGSLYDDVDIMDIC-5.3978-5.5112
HLA-A02:016TDR8609SGSLYDDVDIMDIC-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of KDM4B-KLF11

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-KLF11chr195041262chr210186277817SLYDDVDIMTCTTTGTATGATGACGTTGACATCATG
KDM4B-KLF11chr195041262chr210186277917LYDDVDIMTTGTATGATGACGTTGACATCATG
KDM4B-KLF11chr195041262chr210186277919LYDDVDIMDITTGTATGATGACGTTGACATCATGGACATA

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-KLF11

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-CancerKDM4B-KLF11chr195041262ENST00000159111chr210186277ENST00000305883ERR315469

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Potential target of CAR-T therapy development for KDM4B-KLF11

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-KLF11

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-KLF11

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