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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:ZNF227-AKAP9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZNF227-AKAP9
FusionPDB ID: 101651
FusionGDB2.0 ID: 101651
HgeneTgene
Gene symbol

ZNF227

AKAP9

Gene ID

7770

10142

Gene namezinc finger protein 227A-kinase anchoring protein 9
Synonyms-AKAP-9|AKAP350|AKAP450|CG-NAP|HYPERION|LQT11|MU-RMS-40.16A|PPP1R45|PRKA9|YOTIAO
Cytomap

19q13.31

7q21.2

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein 227A-kinase anchor protein 9A kinase (PRKA) anchor protein (yotiao) 9A kinase (PRKA) anchor protein 9A-kinase anchor protein 350 kDaA-kinase anchor protein 450 kDaAKAP 120-like proteinAKAP9-BRAF fusion proteincentrosome- and Golgi-localized PKN-associ
Modification date2020031320200328
UniProtAcc.

Q99996

Main function of 5'-partner protein: FUNCTION: Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus. Required to maintain the integrity of the Golgi apparatus (PubMed:10202149, PubMed:15047863). Required for microtubule nucleation at the cis-side of the Golgi apparatus (PubMed:15047863, PubMed:19242490). Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase (PubMed:25657325). In complex with PDE4DIP isoform 13/MMG8/SMYLE, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745, PubMed:28814570). In complex with PDE4DIP isoform 13/MMG8/SMYLE, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension also from the centrosome to the cell periphery (PubMed:29162697). {ECO:0000269|PubMed:10202149, ECO:0000269|PubMed:15047863, ECO:0000269|PubMed:19242490, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28814570, ECO:0000269|PubMed:29162697}.; FUNCTION: [Isoform 4]: Associated with the N-methyl-D-aspartate receptor and is specifically found in the neuromuscular junction (NMJ) as well as in neuronal synapses, suggesting a role in the organization of postsynaptic specializations. {ECO:0000269|PubMed:9482789}.
Ensembl transtripts involved in fusion geneENST idsENST00000313040, ENST00000586228, 
ENST00000391961, ENST00000589005, 
ENST00000589237, ENST00000589707, 
ENST00000394564, ENST00000491695, 
ENST00000356239, ENST00000358100, 
ENST00000359028, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 6 X 4=9611 X 17 X 7=1309
# samples 715
** MAII scorelog2(7/96*10)=-0.45567948377619
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1309*10)=-3.12543069144936
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZNF227 [Title/Abstract] AND AKAP9 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZNF227 [Title/Abstract] AND AKAP9 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZNF227(44722005)-AKAP9(91671981), # samples:2
Anticipated loss of major functional domain due to fusion event.ZNF227-AKAP9 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.
ZNF227-AKAP9 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.
ZNF227-AKAP9 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.
ZNF227-AKAP9 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
TgeneAKAP9

GO:0098962

regulation of postsynaptic neurotransmitter receptor activity

10390370

TgeneAKAP9

GO:1903358

regulation of Golgi organization

27666745



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/chr19:44722005/chr7:91671981)
- 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 ZNF227 (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 AKAP9 (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)
ENST00000586228ZNF227chr1944722005+ENST00000356239AKAP9chr791671981+744526511869302270
ENST00000586228ZNF227chr1944722005+ENST00000358100AKAP9chr791671981+725926511867442208
ENST00000586228ZNF227chr1944722005+ENST00000359028AKAP9chr791671981+742126511869062262
ENST00000313040ZNF227chr1944722005+ENST00000356239AKAP9chr791671981+744526511869302270
ENST00000313040ZNF227chr1944722005+ENST00000358100AKAP9chr791671981+725926511867442208
ENST00000313040ZNF227chr1944722005+ENST00000359028AKAP9chr791671981+742126511869062262
ENST00000586228ZNF227chr1944722005+ENST00000356239AKAP9chr791671360+758626511870712317
ENST00000586228ZNF227chr1944722005+ENST00000358100AKAP9chr791671360+740026511868852255
ENST00000586228ZNF227chr1944722005+ENST00000359028AKAP9chr791671360+756226511870472309
ENST00000313040ZNF227chr1944722005+ENST00000356239AKAP9chr791671360+758626511870712317
ENST00000313040ZNF227chr1944722005+ENST00000358100AKAP9chr791671360+740026511868852255
ENST00000313040ZNF227chr1944722005+ENST00000359028AKAP9chr791671360+756226511870472309
ENST00000586228ZNF227chr1944722005+ENST00000356239AKAP9chr791671982+744526511869302270
ENST00000586228ZNF227chr1944722005+ENST00000358100AKAP9chr791671982+725926511867442208
ENST00000586228ZNF227chr1944722005+ENST00000359028AKAP9chr791671982+742126511869062262
ENST00000313040ZNF227chr1944722005+ENST00000356239AKAP9chr791671982+744526511869302270
ENST00000313040ZNF227chr1944722005+ENST00000358100AKAP9chr791671982+725926511867442208
ENST00000313040ZNF227chr1944722005+ENST00000359028AKAP9chr791671982+742126511869062262

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
ENST00000586228ENST00000356239ZNF227chr1944722005+AKAP9chr791671981+0.0026398750.99736017
ENST00000586228ENST00000358100ZNF227chr1944722005+AKAP9chr791671981+0.0026447650.9973552
ENST00000586228ENST00000359028ZNF227chr1944722005+AKAP9chr791671981+0.0023492380.9976508
ENST00000313040ENST00000356239ZNF227chr1944722005+AKAP9chr791671981+0.0026398750.99736017
ENST00000313040ENST00000358100ZNF227chr1944722005+AKAP9chr791671981+0.0026447650.9973552
ENST00000313040ENST00000359028ZNF227chr1944722005+AKAP9chr791671981+0.0023492380.9976508
ENST00000586228ENST00000356239ZNF227chr1944722005+AKAP9chr791671360+0.0025617750.9974382
ENST00000586228ENST00000358100ZNF227chr1944722005+AKAP9chr791671360+0.0025577340.99744225
ENST00000586228ENST00000359028ZNF227chr1944722005+AKAP9chr791671360+0.0022656730.9977343
ENST00000313040ENST00000356239ZNF227chr1944722005+AKAP9chr791671360+0.0025617750.9974382
ENST00000313040ENST00000358100ZNF227chr1944722005+AKAP9chr791671360+0.0025577340.99744225
ENST00000313040ENST00000359028ZNF227chr1944722005+AKAP9chr791671360+0.0022656730.9977343
ENST00000586228ENST00000356239ZNF227chr1944722005+AKAP9chr791671982+0.0026398750.99736017
ENST00000586228ENST00000358100ZNF227chr1944722005+AKAP9chr791671982+0.0026447650.9973552
ENST00000586228ENST00000359028ZNF227chr1944722005+AKAP9chr791671982+0.0023492380.9976508
ENST00000313040ENST00000356239ZNF227chr1944722005+AKAP9chr791671982+0.0026398750.99736017
ENST00000313040ENST00000358100ZNF227chr1944722005+AKAP9chr791671982+0.0026447650.9973552
ENST00000313040ENST00000359028ZNF227chr1944722005+AKAP9chr791671982+0.0023492380.9976508

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 ZNF227-AKAP9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZNF227chr1944722005AKAP9chr79167136026549LPQKKQEKMTKFQRSSIDNENLVSER
ZNF227chr1944722005AKAP9chr79167198126548DLPQKKQEKMTKFQNGNENQGEVEEQ
ZNF227chr1944722005AKAP9chr79167198226548DLPQKKQEKMTKFQNGNENQGEVEEQ

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Potential FusionNeoAntigen Information of ZNF227-AKAP9 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.
ZNF227-AKAP9_44722005_91671360.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)
ZNF227-AKAP9chr1944722005chr791671360265HLA-A30:08MTKFQRSSI0.98060.5254817
ZNF227-AKAP9chr1944722005chr791671360265HLA-B38:02QRSSIDNENL0.98490.93521222
ZNF227-AKAP9chr1944722005chr791671360265HLA-B27:09QRSSIDNENL0.99880.84041222

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Potential FusionNeoAntigen Information of ZNF227-AKAP9 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.
ZNF227-AKAP9_44722005_91671360.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)
ZNF227-AKAP9chr1944722005chr791671360265DRB1-1343QEKMTKFQRSSIDNE520
ZNF227-AKAP9chr1944722005chr791671360265DRB1-1354QEKMTKFQRSSIDNE520
ZNF227-AKAP9chr1944722005chr791671360265DRB1-1416QEKMTKFQRSSIDNE520

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Fusion breakpoint peptide structures of ZNF227-AKAP9

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
1850EKMTKFQRSSIDNEZNF227AKAP9chr1944722005chr791671360265

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZNF227-AKAP9

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-B14:023BVN1850EKMTKFQRSSIDNE-7.9962-8.1096
HLA-B14:023BVN1850EKMTKFQRSSIDNE-5.70842-6.74372
HLA-B52:013W391850EKMTKFQRSSIDNE-6.83737-6.95077
HLA-B52:013W391850EKMTKFQRSSIDNE-4.4836-5.5189
HLA-A11:014UQ21850EKMTKFQRSSIDNE-10.0067-10.1201
HLA-A11:014UQ21850EKMTKFQRSSIDNE-9.03915-10.0745
HLA-A24:025HGA1850EKMTKFQRSSIDNE-6.56204-6.67544
HLA-A24:025HGA1850EKMTKFQRSSIDNE-5.42271-6.45801
HLA-B44:053DX81850EKMTKFQRSSIDNE-7.85648-8.89178
HLA-B44:053DX81850EKMTKFQRSSIDNE-5.3978-5.5112
HLA-A02:016TDR1850EKMTKFQRSSIDNE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ZNF227-AKAP9

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
ZNF227-AKAP9chr1944722005chr7916713601222QRSSIDNENLCAGAGATCCTCCATAGATAATGAAAACCTG
ZNF227-AKAP9chr1944722005chr791671360817MTKFQRSSIATGACCAAGTTTCAGAGATCCTCCATA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ZNF227-AKAP9chr1944722005chr791671360520QEKMTKFQRSSIDNECAGGAGAAAATGACCAAGTTTCAGAGATCCTCCATAGATAATGAA

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Information of the samples that have these potential fusion neoantigens of ZNF227-AKAP9

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
STADZNF227-AKAP9chr1944722005ENST00000313040chr791671360ENST00000356239TCGA-BR-A4PD-01A

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Potential target of CAR-T therapy development for ZNF227-AKAP9

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 ZNF227-AKAP9

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 ZNF227-AKAP9

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
TgeneAKAP9C2678483Long Qt Syndrome 114CLINGEN;CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneAKAP9C0035828Romano-Ward Syndrome1ORPHANET
TgeneAKAP9C0037274Dermatologic disorders1CTD_human
TgeneAKAP9C0274861Arsenic Poisoning, Inorganic1CTD_human
TgeneAKAP9C0274862Nervous System, Organic Arsenic Poisoning1CTD_human
TgeneAKAP9C0311375Arsenic Poisoning1CTD_human
TgeneAKAP9C0751851Arsenic Encephalopathy1CTD_human
TgeneAKAP9C0751852Arsenic Induced Polyneuropathy1CTD_human
TgeneAKAP9C1142166Brugada Syndrome (disorder)1ORPHANET