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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:KMT2C-IRF5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KMT2C-IRF5
FusionPDB ID: 43250
FusionGDB2.0 ID: 54208
HgeneTgene
Gene symbol

KMT2C

IRF5

Gene ID

58508

3663

Gene namelysine methyltransferase 2Cinterferon regulatory factor 5
SynonymsHALR|KLEFS2|MLL3SLEB10
Cytomap

7q36.1

7q32.1

Type of geneprotein-codingprotein-coding
Descriptionhistone-lysine N-methyltransferase 2CALR-like proteinhistone-lysine N-methyltransferase MLL3histone-lysine N-methyltransferase, H3 lysine-4 specifichomologous to ALR proteinlysine (K)-specific methyltransferase 2Cmyeloid/lymphoid or mixed-lineage leinterferon regulatory factor 5
Modification date2020032020200315
UniProtAcc

Q8NEZ4

Main function of 5'-partner protein: FUNCTION: Histone methyltransferase that methylates 'Lys-4' of histone H3 (PubMed:22266653). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Central component of the MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation. KMT2C/MLL3 may be a catalytic subunit of this complex. May be involved in leukemogenesis and developmental disorder. {ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:22266653}.

Q13568

Main function of 5'-partner protein: FUNCTION: Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:11303025, PubMed:15695821, PubMed:22412986, PubMed:25326418, PubMed:32433612). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (By similarity). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (By similarity). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000250|UniProtKB:P56477, ECO:0000269|PubMed:11303025, ECO:0000269|PubMed:15695821, ECO:0000269|PubMed:22412986, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:32433612, ECO:0000269|PubMed:33440148}.
Ensembl transtripts involved in fusion geneENST idsENST00000262189, ENST00000355193, 
ENST00000485241, ENST00000485655, 
ENST00000249375, ENST00000357234, 
ENST00000402030, ENST00000473745, 
ENST00000477535, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score26 X 23 X 12=71761 X 2 X 1=2
# samples 321
** MAII scorelog2(32/7176*10)=-4.4870360800319
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/2*10)=2.32192809488736
Fusion gene context

PubMed: KMT2C [Title/Abstract] AND IRF5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KMT2C [Title/Abstract] AND IRF5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KMT2C(151980068)-IRF5(128582125), # samples:2
Anticipated loss of major functional domain due to fusion event.KMT2C-IRF5 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.
KMT2C-IRF5 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.
KMT2C-IRF5 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.
KMT2C-IRF5 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
HgeneKMT2C

GO:0097692

histone H3-K4 monomethylation

26324722

TgeneIRF5

GO:0032494

response to peptidoglycan

22412986

TgeneIRF5

GO:0032495

response to muramyl dipeptide

22412986

TgeneIRF5

GO:0045944

positive regulation of transcription by RNA polymerase II

12600985|22412986



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/chr7:151980068/chr7:128582125)
- 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 KMT2C (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 IRF5 (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)
ENST00000262189KMT2Cchr7152007051-ENST00000477535IRF5chr7128585899+212610682072111634
ENST00000262189KMT2Cchr7152007051-ENST00000357234IRF5chr7128585899+243210682072417736
ENST00000262189KMT2Cchr7152007051-ENST00000402030IRF5chr7128585899+358710682072369720
ENST00000262189KMT2Cchr7152007051-ENST00000249375IRF5chr7128585899+358210682072369720
ENST00000262189KMT2Cchr7152007051-ENST00000473745IRF5chr7128585899+294010682072369720
ENST00000355193KMT2Cchr7152007051-ENST00000477535IRF5chr7128585899+212610682072111634
ENST00000355193KMT2Cchr7152007051-ENST00000357234IRF5chr7128585899+243210682072417736
ENST00000355193KMT2Cchr7152007051-ENST00000402030IRF5chr7128585899+358710682072369720
ENST00000355193KMT2Cchr7152007051-ENST00000249375IRF5chr7128585899+358210682072369720
ENST00000355193KMT2Cchr7152007051-ENST00000473745IRF5chr7128585899+294010682072369720

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
ENST00000262189ENST00000477535KMT2Cchr7152007051-IRF5chr7128585899+0.0084010120.99159896
ENST00000262189ENST00000357234KMT2Cchr7152007051-IRF5chr7128585899+0.0117020620.988298
ENST00000262189ENST00000402030KMT2Cchr7152007051-IRF5chr7128585899+0.0042377850.9957623
ENST00000262189ENST00000249375KMT2Cchr7152007051-IRF5chr7128585899+0.0043107310.9956892
ENST00000262189ENST00000473745KMT2Cchr7152007051-IRF5chr7128585899+0.0073686260.99263144
ENST00000355193ENST00000477535KMT2Cchr7152007051-IRF5chr7128585899+0.0084010120.99159896
ENST00000355193ENST00000357234KMT2Cchr7152007051-IRF5chr7128585899+0.0117020620.988298
ENST00000355193ENST00000402030KMT2Cchr7152007051-IRF5chr7128585899+0.0042377850.9957623
ENST00000355193ENST00000249375KMT2Cchr7152007051-IRF5chr7128585899+0.0043107310.9956892
ENST00000355193ENST00000473745KMT2Cchr7152007051-IRF5chr7128585899+0.0073686260.99263144

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 KMT2C-IRF5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KMT2Cchr7152007051IRF5chr71285858991068287VNVDKAVVSGSTEAWAKETGKYTEGV

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Potential FusionNeoAntigen Information of KMT2C-IRF5 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.
KMT2C-IRF5_152007051_128585899.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)
KMT2C-IRF5chr7152007051chr71285858991068HLA-B58:01VSGSTEAW0.99850.9926715
KMT2C-IRF5chr7152007051chr71285858991068HLA-B58:01VVSGSTEAW0.98430.9914615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B15:17VVSGSTEAW0.98370.9562615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B15:16VVSGSTEAW0.97390.9665615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:01VVSGSTEAW0.9690.9938615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B58:02VVSGSTEAW0.95260.9906615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:03VVSGSTEAW0.82030.9959615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B53:01VVSGSTEAW0.75760.8063615
KMT2C-IRF5chr7152007051chr71285858991068HLA-A31:08VVSGSTEAW0.6450.7696615
KMT2C-IRF5chr7152007051chr71285858991068HLA-A32:13VVSGSTEAW0.47950.9845615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B58:01AVVSGSTEAW0.99280.9886515
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:01KAVVSGSTEAW0.99990.9882415
KMT2C-IRF5chr7152007051chr71285858991068HLA-B44:03TEAWAKETGKY0.99980.97911122
KMT2C-IRF5chr7152007051chr71285858991068HLA-B58:02KAVVSGSTEAW0.99980.9809415
KMT2C-IRF5chr7152007051chr71285858991068HLA-B58:01KAVVSGSTEAW0.99950.9822415
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:03KAVVSGSTEAW0.9990.9916415
KMT2C-IRF5chr7152007051chr71285858991068HLA-B15:17KAVVSGSTEAW0.99870.9327415
KMT2C-IRF5chr7152007051chr71285858991068HLA-B44:06VVSGSTEAW0.03760.6211615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B44:08TEAWAKETGKY0.99990.52431122
KMT2C-IRF5chr7152007051chr71285858991068HLA-B44:09TEAWAKETGKY0.99980.58051122
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:04VVSGSTEAW0.99430.85615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:02VVSGSTEAW0.96960.9867615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:10VVSGSTEAW0.9690.9938615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B15:13VVSGSTEAW0.94820.9565615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B58:06VVSGSTEAW0.94720.9859615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B15:24VVSGSTEAW0.90150.9878615
KMT2C-IRF5chr7152007051chr71285858991068HLA-A32:01VVSGSTEAW0.75790.9788615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B53:02VVSGSTEAW0.54460.7824615
KMT2C-IRF5chr7152007051chr71285858991068HLA-A25:01VVSGSTEAW0.4350.857615
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:04AVVSGSTEAW0.99890.8682515
KMT2C-IRF5chr7152007051chr71285858991068HLA-B15:24AVVSGSTEAW0.98930.9805515
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:02AVVSGSTEAW0.98450.988515
KMT2C-IRF5chr7152007051chr71285858991068HLA-B15:13AVVSGSTEAW0.97080.9519515
KMT2C-IRF5chr7152007051chr71285858991068HLA-A25:01EAWAKETGKY0.9530.9061222
KMT2C-IRF5chr7152007051chr71285858991068HLA-A32:01AVVSGSTEAW0.84240.966515
KMT2C-IRF5chr7152007051chr71285858991068HLA-A25:01AVVSGSTEAW0.72380.894515
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:10KAVVSGSTEAW0.99990.9882415
KMT2C-IRF5chr7152007051chr71285858991068HLA-B58:06KAVVSGSTEAW0.99980.9778415
KMT2C-IRF5chr7152007051chr71285858991068HLA-B44:26TEAWAKETGKY0.99980.97911122
KMT2C-IRF5chr7152007051chr71285858991068HLA-B44:13TEAWAKETGKY0.99980.97911122
KMT2C-IRF5chr7152007051chr71285858991068HLA-B44:07TEAWAKETGKY0.99980.97911122
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:04KAVVSGSTEAW0.99970.8818415
KMT2C-IRF5chr7152007051chr71285858991068HLA-B57:02KAVVSGSTEAW0.99780.9878415
KMT2C-IRF5chr7152007051chr71285858991068HLA-B18:11TEAWAKETGKY0.99720.94541122
KMT2C-IRF5chr7152007051chr71285858991068HLA-A32:01KAVVSGSTEAW0.9960.9734415

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Potential FusionNeoAntigen Information of KMT2C-IRF5 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 KMT2C-IRF5

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
10372VVSGSTEAWAKETGKMT2CIRF5chr7152007051chr71285858991068

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KMT2C-IRF5

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-B14:023BVN10372VVSGSTEAWAKETG-6.80686-6.92026
HLA-B14:023BVN10372VVSGSTEAWAKETG-5.01234-6.04764
HLA-B52:013W3910372VVSGSTEAWAKETG-6.71251-6.82591
HLA-B52:013W3910372VVSGSTEAWAKETG-4.13165-5.16695
HLA-A11:014UQ210372VVSGSTEAWAKETG-4.31699-4.43039
HLA-A11:014UQ210372VVSGSTEAWAKETG-4.19959-5.23489
HLA-A24:025HGA10372VVSGSTEAWAKETG-7.74913-7.86253
HLA-A24:025HGA10372VVSGSTEAWAKETG-5.75888-6.79418
HLA-B27:036PZ510372VVSGSTEAWAKETG1000110000
HLA-B44:053DX810372VVSGSTEAWAKETG-4.89721-5.01061
HLA-B44:053DX810372VVSGSTEAWAKETG-3.74482-4.78012
HLA-B35:011A1N10372VVSGSTEAWAKETG-8.42572-8.53912
HLA-B35:011A1N10372VVSGSTEAWAKETG-6.4428-7.4781
HLA-A02:016TDR10372VVSGSTEAWAKETG-5.01451-6.04981

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Vaccine Design for the FusionNeoAntigens of KMT2C-IRF5

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
KMT2C-IRF5chr7152007051chr71285858991122TEAWAKETGKYACAGAAGCCTGGGCCAAGGAGACAGGGAAATAC
KMT2C-IRF5chr7152007051chr71285858991222EAWAKETGKYGAAGCCTGGGCCAAGGAGACAGGGAAATAC
KMT2C-IRF5chr7152007051chr7128585899415KAVVSGSTEAWAAAGCTGTTGTCTCAGGGAGCACAGAAGCCTGG
KMT2C-IRF5chr7152007051chr7128585899515AVVSGSTEAWGCTGTTGTCTCAGGGAGCACAGAAGCCTGG
KMT2C-IRF5chr7152007051chr7128585899615VVSGSTEAWGTTGTCTCAGGGAGCACAGAAGCCTGG
KMT2C-IRF5chr7152007051chr7128585899715VSGSTEAWGTCTCAGGGAGCACAGAAGCCTGG

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 KMT2C-IRF5

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
SKCMKMT2C-IRF5chr7152007051ENST00000262189chr7128585899ENST00000249375TCGA-D3-A3C3-06A

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Potential target of CAR-T therapy development for KMT2C-IRF5

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 KMT2C-IRF5

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 KMT2C-IRF5

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