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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:KAT2B-KANSL1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KAT2B-KANSL1
FusionPDB ID: 41186
FusionGDB2.0 ID: 41186
HgeneTgene
Gene symbol

KAT2B

KANSL1

Gene ID

8850

284058

Gene namelysine acetyltransferase 2BKAT8 regulatory NSL complex subunit 1
SynonymsCAF|P/CAF|PCAFCENP-36|KDVS|KIAA1267|MSL1v1|NSL1|hMSL1v1
Cytomap

3p24.3

17q21.31

Type of geneprotein-codingprotein-coding
Descriptionhistone acetyltransferase KAT2BCREBBP-associated factorK(lysine) acetyltransferase 2Bhistone acetylase PCAFhistone acetyltransferase PCAFp300/CBP-associated factorspermidine acetyltransferase KAT2BKAT8 regulatory NSL complex subunit 1MLL1/MLL complex subunit KANSL1MSL1 homolog 1NSL complex protein NSL1centromere protein 36male-specific lethal 1 homolognon-specific lethal 1 homolog
Modification date2020031320200327
UniProtAcc

Q92831

Main function of 5'-partner protein: FUNCTION: Functions as a histone acetyltransferase (HAT) to promote transcriptional activation (PubMed:8945521). Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles (PubMed:8945521). Also acetylates non-histone proteins, such as ACLY, PLK4, RRP9/U3-55K and TBX5 (PubMed:9707565, PubMed:10675335, PubMed:27796307, PubMed:23932781, PubMed:26867678, PubMed:29174768). Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A (PubMed:8684459). Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers (PubMed:14645221). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acetylates RRP9/U3-55K, a core subunit of the U3 snoRNP complex, impairing pre-rRNA processing (PubMed:26867678). Also acetylates spermidine (PubMed:27389534). {ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:26867678, ECO:0000269|PubMed:27389534, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:8684459, ECO:0000269|PubMed:8945521, ECO:0000269|PubMed:9707565}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. {ECO:0000269|PubMed:12486002}.

A0AUZ9

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000426228, ENST00000263754, 
ENST00000262419, ENST00000432791, 
ENST00000572904, ENST00000574590, 
ENST00000575318, ENST00000393476, 
ENST00000576248, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 2=3217 X 18 X 11=3366
# samples 428
** MAII scorelog2(4/32*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(28/3366*10)=-3.58753644438498
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KAT2B [Title/Abstract] AND KANSL1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KAT2B [Title/Abstract] AND KANSL1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KAT2B(20136900)-KANSL1(44145033), # samples:1
Anticipated loss of major functional domain due to fusion event.KAT2B-KANSL1 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.
KAT2B-KANSL1 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.
KAT2B-KANSL1 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.
KAT2B-KANSL1 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
HgeneKAT2B

GO:0006338

chromatin remodeling

17707232

HgeneKAT2B

GO:0006473

protein acetylation

15273251|26867678

HgeneKAT2B

GO:0008285

negative regulation of cell proliferation

8684459

HgeneKAT2B

GO:0010835

regulation of protein ADP-ribosylation

19470756

HgeneKAT2B

GO:0018076

N-terminal peptidyl-lysine acetylation

12435739

HgeneKAT2B

GO:0018393

internal peptidyl-lysine acetylation

23932781|27796307|29174768

HgeneKAT2B

GO:0018394

peptidyl-lysine acetylation

19303849|19470756

HgeneKAT2B

GO:0032869

cellular response to insulin stimulus

19303849

HgeneKAT2B

GO:0043966

histone H3 acetylation

18838386

HgeneKAT2B

GO:0045944

positive regulation of transcription by RNA polymerase II

19470756

HgeneKAT2B

GO:0046600

negative regulation of centriole replication

27796307

HgeneKAT2B

GO:2000233

negative regulation of rRNA processing

26867678

TgeneKANSL1

GO:0043981

histone H4-K5 acetylation

20018852

TgeneKANSL1

GO:0043982

histone H4-K8 acetylation

20018852

TgeneKANSL1

GO:0043984

histone H4-K16 acetylation

20018852



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/chr3:20136900/chr17:44145033)
- 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 KAT2B (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 KANSL1 (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)
ENST00000263754KAT2Bchr320136900+ENST00000574590KANSL1chr1744145033-437610314552815786
ENST00000263754KAT2Bchr320136900+ENST00000575318KANSL1chr1744145033-417510314552623722
ENST00000263754KAT2Bchr320136900+ENST00000572904KANSL1chr1744145033-433910314552815786
ENST00000263754KAT2Bchr320136900+ENST00000262419KANSL1chr1744145033-433610314552815786
ENST00000263754KAT2Bchr320136900+ENST00000432791KANSL1chr1744145033-432410314552815786

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
ENST00000263754ENST00000574590KAT2Bchr320136900+KANSL1chr1744145033-0.0071104660.9928895
ENST00000263754ENST00000575318KAT2Bchr320136900+KANSL1chr1744145033-0.0108965750.98910344
ENST00000263754ENST00000572904KAT2Bchr320136900+KANSL1chr1744145033-0.0078920.9921079
ENST00000263754ENST00000262419KAT2Bchr320136900+KANSL1chr1744145033-0.0078599410.9921401
ENST00000263754ENST00000432791KAT2Bchr320136900+KANSL1chr1744145033-0.0084442780.99155575

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 KAT2B-KANSL1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KAT2Bchr320136900KANSL1chr17441450331031192DADTKQVYFYLFKIESVSQPLENHGA

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Potential FusionNeoAntigen Information of KAT2B-KANSL1 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.
KAT2B-KANSL1_20136900_44145033.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)
KAT2B-KANSL1chr320136900chr17441450331031HLA-A02:13YLFKIESV0.9940.5034917
KAT2B-KANSL1chr320136900chr17441450331031HLA-A02:21YLFKIESV0.99380.5733917
KAT2B-KANSL1chr320136900chr17441450331031HLA-A02:04YLFKIESV0.99320.5183917
KAT2B-KANSL1chr320136900chr17441450331031HLA-B08:09FYLFKIESV0.920.5856817
KAT2B-KANSL1chr320136900chr17441450331031HLA-A02:07YLFKIESV0.99730.5055917
KAT2B-KANSL1chr320136900chr17441450331031HLA-C04:14FYLFKIESV0.30460.5093817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:05FYLFKIESV0.18350.9455817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:19FYLFKIESV0.1740.5393817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:67FYLFKIESV0.15050.9404817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:80FYLFKIESV0.15050.9404817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:10FYLFKIESV0.14220.9657817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:29FYLFKIESV0.1240.8899817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:13FYLFKIESV0.06880.8461817
KAT2B-KANSL1chr320136900chr17441450331031HLA-A02:03YLFKIESV0.99660.581917
KAT2B-KANSL1chr320136900chr17441450331031HLA-A02:06YLFKIESV0.99380.5733917
KAT2B-KANSL1chr320136900chr17441450331031HLA-C06:17FYLFKIESV0.47810.9951817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C06:02FYLFKIESV0.47810.9951817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C04:04FYLFKIESV0.3250.6839817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:04FYLFKIESV0.17420.906817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:02FYLFKIESV0.15050.9404817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C06:06FYLFKIESV0.14080.9836817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C06:08FYLFKIESV0.13290.9917817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C07:17FYLFKIESV0.0980.9772817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C14:02FYLFKIESV0.07970.9596817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C14:03FYLFKIESV0.07970.9596817
KAT2B-KANSL1chr320136900chr17441450331031HLA-C03:67FYLFKIESV0.06260.9793817

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Potential FusionNeoAntigen Information of KAT2B-KANSL1 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.
KAT2B-KANSL1_20136900_44145033.msa

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)
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1105KQVYFYLFKIESVSQ419
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1108KQVYFYLFKIESVSQ419
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1119KQVYFYLFKIESVSQ419
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1127KQVYFYLFKIESVSQ419
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1131KQVYFYLFKIESVSQ419
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1132KQVYFYLFKIESVSQ419
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1145KQVYFYLFKIESVSQ419
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1356KQVYFYLFKIESVSQ419
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1382KQVYFYLFKIESVSQ419
KAT2B-KANSL1chr320136900chr17441450331031DRB1-1430KQVYFYLFKIESVSQ419

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Fusion breakpoint peptide structures of KAT2B-KANSL1

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
10398VYFYLFKIESVSQPKAT2BKANSL1chr320136900chr17441450331031

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KAT2B-KANSL1

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-B14:023BVN10398VYFYLFKIESVSQP-7.15543-7.26883
HLA-B14:023BVN10398VYFYLFKIESVSQP-4.77435-5.80965
HLA-B52:013W3910398VYFYLFKIESVSQP-6.80875-6.92215
HLA-B52:013W3910398VYFYLFKIESVSQP-4.20386-5.23916
HLA-A11:014UQ210398VYFYLFKIESVSQP-7.5194-8.5547
HLA-A11:014UQ210398VYFYLFKIESVSQP-6.9601-7.0735
HLA-A24:025HGA10398VYFYLFKIESVSQP-7.52403-7.63743
HLA-A24:025HGA10398VYFYLFKIESVSQP-5.82433-6.85963
HLA-B27:056PYJ10398VYFYLFKIESVSQP-3.28285-4.31815
HLA-B44:053DX810398VYFYLFKIESVSQP-5.91172-6.94702
HLA-B44:053DX810398VYFYLFKIESVSQP-4.24346-4.35686
HLA-B35:011A1N10398VYFYLFKIESVSQP-5.9251-6.0385
HLA-B35:011A1N10398VYFYLFKIESVSQP-4.80237-5.83767

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Vaccine Design for the FusionNeoAntigens of KAT2B-KANSL1

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
KAT2B-KANSL1chr320136900chr1744145033817FYLFKIESVTTCTATCTATTTAAGATTGAGTCTGTT
KAT2B-KANSL1chr320136900chr1744145033917YLFKIESVTATCTATTTAAGATTGAGTCTGTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
KAT2B-KANSL1chr320136900chr1744145033419KQVYFYLFKIESVSQAAACAAGTTTATTTCTATCTATTTAAGATTGAGTCTGTTTCTCAG

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Information of the samples that have these potential fusion neoantigens of KAT2B-KANSL1

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-CancerKAT2B-KANSL1chr320136900ENST00000263754chr1744145033ENST00000262419ERR315398

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Potential target of CAR-T therapy development for KAT2B-KANSL1

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 KAT2B-KANSL1

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 KAT2B-KANSL1

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