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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:KAT6A-NCOA2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KAT6A-NCOA2
FusionPDB ID: 41213
FusionGDB2.0 ID: 41213
HgeneTgene
Gene symbol

KAT6A

NCOA2

Gene ID

7994

10499

Gene namelysine acetyltransferase 6Anuclear receptor coactivator 2
SynonymsARTHS|MOZ|MRD32|MYST-3|MYST3|RUNXBP2|ZC2HC6A|ZNF220GRIP1|KAT13C|NCoA-2|SRC2|TIF2|bHLHe75
Cytomap

8p11.21

8q13.3

Type of geneprotein-codingprotein-coding
Descriptionhistone acetyltransferase KAT6AK(lysine) acetyltransferase 6AMOZ, YBF2/SAS3, SAS2 and TIP60 protein 3MYST histone acetyltransferase (monocytic leukemia) 3histone acetyltransferase MYST3monocytic leukemia zinc finger proteinrunt-related transcriptionnuclear receptor coactivator 2class E basic helix-loop-helix protein 75glucocorticoid receptor-interacting protein-1p160 steroid receptor coactivator 2transcriptional intermediary factor 2
Modification date2020031320200313
UniProtAcc

Q92794

Main function of 5'-partner protein: FUNCTION: Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2. Acetylates p53/TP53 at 'Lys-120' and 'Lys-382' and controls its transcriptional activity via association with PML. {ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:12771199, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:17925393, ECO:0000269|PubMed:23431171}.

Q15596

Main function of 5'-partner protein: FUNCTION: Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC1 expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-ARNTL/BMAL1 heterodimer (By similarity). {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:9430642}.
Ensembl transtripts involved in fusion geneENST idsENST00000265713, ENST00000396930, 
ENST00000406337, ENST00000485568, 
ENST00000267974, ENST00000524223, 
ENST00000452400, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score26 X 32 X 13=1081619 X 24 X 6=2736
# samples 4212
** MAII scorelog2(42/10816*10)=-4.68663391861606
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/2736*10)=-4.51096191927738
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KAT6A [Title/Abstract] AND NCOA2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KAT6A [Title/Abstract] AND NCOA2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KAT6A(41794848)-NCOA2(71053441), # samples:1
KAT6A(41794774)-NCOA2(71057084), # samples:1
Anticipated loss of major functional domain due to fusion event.KAT6A-NCOA2 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.
KAT6A-NCOA2 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.
KAT6A-NCOA2 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.
KAT6A-NCOA2 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.
KAT6A-NCOA2 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
KAT6A-NCOA2 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
KAT6A-NCOA2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
KAT6A-NCOA2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
KAT6A-NCOA2 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
KAT6A-NCOA2 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
KAT6A-NCOA2 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
KAT6A-NCOA2 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
KAT6A-NCOA2 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted 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
HgeneKAT6A

GO:0006473

protein acetylation

23431171

HgeneKAT6A

GO:0016573

histone acetylation

11742995|17925393

HgeneKAT6A

GO:0030099

myeloid cell differentiation

11742995

HgeneKAT6A

GO:0043966

histone H3 acetylation

16387653

HgeneKAT6A

GO:0045892

negative regulation of transcription, DNA-templated

11742995

HgeneKAT6A

GO:0045893

positive regulation of transcription, DNA-templated

11742995|11965546|18794358



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/chr8:41794848/chr8:71053441)
- 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 KAT6A (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 NCOA2 (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)
ENST00000265713KAT6Achr841794774-ENST00000452400NCOA2chr871057084-9424376441255531713
ENST00000396930KAT6Achr841794774-ENST00000452400NCOA2chr871057084-9556389654456851713

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
ENST00000265713ENST00000452400KAT6Achr841794774-NCOA2chr871057084-0.0001909150.9998091
ENST00000396930ENST00000452400KAT6Achr841794774-NCOA2chr871057084-0.0002205140.9997795

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 KAT6A-NCOA2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KAT6Achr841794774NCOA2chr87105708437641117KDEEEDEESDDADAFNNPRPGQLGRL
KAT6Achr841794774NCOA2chr87105708438961117KDEEEDEESDDADAFNNPRPGQLGRL

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Potential FusionNeoAntigen Information of KAT6A-NCOA2 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.
KAT6A-NCOA2_41794774_71057084.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)
KAT6A-NCOA2chr841794774chr8710570843764HLA-B44:03EESDDADAF0.97460.6895615
KAT6A-NCOA2chr841794774chr8710570843764HLA-B44:26EESDDADAF0.97460.6895615
KAT6A-NCOA2chr841794774chr8710570843764HLA-B44:07EESDDADAF0.97460.6895615
KAT6A-NCOA2chr841794774chr8710570843764HLA-B44:13EESDDADAF0.97460.6895615

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Potential FusionNeoAntigen Information of KAT6A-NCOA2 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 KAT6A-NCOA2

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
1697EESDDADAFNNPRPKAT6ANCOA2chr841794774chr8710570843764

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KAT6A-NCOA2

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-B14:023BVN1697EESDDADAFNNPRP-7.15543-7.26883
HLA-B14:023BVN1697EESDDADAFNNPRP-4.77435-5.80965
HLA-B52:013W391697EESDDADAFNNPRP-6.80875-6.92215
HLA-B52:013W391697EESDDADAFNNPRP-4.20386-5.23916
HLA-A11:014UQ21697EESDDADAFNNPRP-7.5194-8.5547
HLA-A11:014UQ21697EESDDADAFNNPRP-6.9601-7.0735
HLA-A24:025HGA1697EESDDADAFNNPRP-7.52403-7.63743
HLA-A24:025HGA1697EESDDADAFNNPRP-5.82433-6.85963
HLA-B27:056PYJ1697EESDDADAFNNPRP-3.28285-4.31815
HLA-B44:053DX81697EESDDADAFNNPRP-5.91172-6.94702
HLA-B44:053DX81697EESDDADAFNNPRP-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of KAT6A-NCOA2

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
KAT6A-NCOA2chr841794774chr871057084615EESDDADAFAAGAGTCAGATGATGCTGATGCTTTTA

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 KAT6A-NCOA2

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
N/AKAT6A-NCOA2chr841794774ENST00000265713chr871057084ENST00000452400EF374064

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Potential target of CAR-T therapy development for KAT6A-NCOA2

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 KAT6A-NCOA2

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 KAT6A-NCOA2

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
HgeneKAT6AC4225396MENTAL RETARDATION, AUTOSOMAL DOMINANT 323CTD_human;GENOMICS_ENGLAND;ORPHANET
HgeneKAT6AC4511003Acute myeloid leukemia with t(8;16)(p11;p13) translocation2ORPHANET
HgeneKAT6AC0010606Adenoid Cystic Carcinoma1CTD_human
HgeneKAT6AC0025149Medulloblastoma1CTD_human
HgeneKAT6AC0033578Prostatic Neoplasms1CTD_human
HgeneKAT6AC0205833Medullomyoblastoma1CTD_human
HgeneKAT6AC0278510Childhood Medulloblastoma1CTD_human
HgeneKAT6AC0278876Adult Medulloblastoma1CTD_human
HgeneKAT6AC0376358Malignant neoplasm of prostate1CTD_human
HgeneKAT6AC0751291Desmoplastic Medulloblastoma1CTD_human
HgeneKAT6AC1275668Melanotic medulloblastoma1CTD_human
TgeneNCOA2C0006142Malignant neoplasm of breast1CTD_human
TgeneNCOA2C0033578Prostatic Neoplasms1CTD_human
TgeneNCOA2C0376358Malignant neoplasm of prostate1CTD_human
TgeneNCOA2C0678222Breast Carcinoma1CTD_human
TgeneNCOA2C1257931Mammary Neoplasms, Human1CTD_human
TgeneNCOA2C1458155Mammary Neoplasms1CTD_human
TgeneNCOA2C4704874Mammary Carcinoma, Human1CTD_human