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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:ANKRD17-PAK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ANKRD17-PAK1
FusionPDB ID: 4606
FusionGDB2.0 ID: 4606
HgeneTgene
Gene symbol

ANKRD17

PAK1

Gene ID

26057

5585

Gene nameankyrin repeat domain 17protein kinase N1
SynonymsGTAR|MASK2|NY-BR-16DBK|PAK-1|PAK1|PKN|PKN-ALPHA|PRK1|PRKCL1
Cytomap

4q13.3

19p13.12

Type of geneprotein-codingprotein-coding
Descriptionankyrin repeat domain-containing protein 17gene trap ankyrin repeat proteinserologically defined breast cancer antigen NY-BR-16serine/threonine-protein kinase N1protease-activated kinase 1protein kinase C-like 1protein kinase C-like PKNprotein kinase C-related kinase 1protein kinase PKN-alphaserine-threonine kinase Nserine/threonine protein kinase N
Modification date2020031320200329
UniProtAcc

O75179

Main function of 5'-partner protein: FUNCTION: Could play pivotal roles in cell cycle and DNA regulation (PubMed:19150984). Involved in innate immune defense against viruse by positively regulating the viral dsRNA receptors DDX58 and IFIH1 signaling pathways (PubMed:22328336). Involves in NOD2- and NOD1-mediated responses to bacteria suggesting a role in innate antibacterial immune pathways too (PubMed:23711367). Target of enterovirus 71 which is the major etiological agent of HFMD (hand, foot and mouth disease) (PubMed:17276651). Could play a central role for the formation and/or maintenance of the blood vessels of the circulation system (By similarity). {ECO:0000250|UniProtKB:Q99NH0, ECO:0000269|PubMed:17276651, ECO:0000269|PubMed:19150984, ECO:0000269|PubMed:22328336, ECO:0000269|PubMed:23711367}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000330838, ENST00000358602, 
ENST00000509867, ENST00000514252, 
ENST00000525542, ENST00000278568, 
ENST00000356341, ENST00000528203, 
ENST00000530617, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 22 X 6=184822 X 17 X 10=3740
# samples 2526
** MAII scorelog2(25/1848*10)=-2.88596475675397
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(26/3740*10)=-3.84645474174655
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ANKRD17 [Title/Abstract] AND PAK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ANKRD17 [Title/Abstract] AND PAK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ANKRD17(74123992)-PAK1(77070062), # samples:1
Anticipated loss of major functional domain due to fusion event.ANKRD17-PAK1 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.
ANKRD17-PAK1 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.
ANKRD17-PAK1 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.
ANKRD17-PAK1 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
HgeneANKRD17

GO:0042742

defense response to bacterium

23711367

HgeneANKRD17

GO:0043123

positive regulation of I-kappaB kinase/NF-kappaB signaling

22328336

HgeneANKRD17

GO:0045087

innate immune response

23711367

HgeneANKRD17

GO:1900245

positive regulation of MDA-5 signaling pathway

22328336

HgeneANKRD17

GO:1900246

positive regulation of RIG-I signaling pathway

22328336

TgenePAK1

GO:0006357

regulation of transcription by RNA polymerase II

12514133

TgenePAK1

GO:0006468

protein phosphorylation

17332740

TgenePAK1

GO:0035407

histone H3-T11 phosphorylation

18066052



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/chr4:74123992/chr11:77070062)
- 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 ANKRD17 (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 PAK1 (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)
ENST00000358602ANKRD17chr474123992-ENST00000356341PAK1chr1177070062-32385101111670519
ENST00000358602ANKRD17chr474123992-ENST00000530617PAK1chr1177070062-27225101111601496
ENST00000358602ANKRD17chr474123992-ENST00000278568PAK1chr1177070062-20465101111694527
ENST00000358602ANKRD17chr474123992-ENST00000528203PAK1chr1177070062-19705101111694527
ENST00000330838ANKRD17chr474123992-ENST00000356341PAK1chr1177070062-32515231241683519
ENST00000330838ANKRD17chr474123992-ENST00000530617PAK1chr1177070062-27355231241614496
ENST00000330838ANKRD17chr474123992-ENST00000278568PAK1chr1177070062-20595231241707527
ENST00000330838ANKRD17chr474123992-ENST00000528203PAK1chr1177070062-19835231241707527

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
ENST00000358602ENST00000356341ANKRD17chr474123992-PAK1chr1177070062-0.0013619830.998638
ENST00000358602ENST00000530617ANKRD17chr474123992-PAK1chr1177070062-0.0014979080.99850214
ENST00000358602ENST00000278568ANKRD17chr474123992-PAK1chr1177070062-0.0046431920.99535674
ENST00000358602ENST00000528203ANKRD17chr474123992-PAK1chr1177070062-0.0052919690.99470806
ENST00000330838ENST00000356341ANKRD17chr474123992-PAK1chr1177070062-0.0013809830.99861896
ENST00000330838ENST00000530617ANKRD17chr474123992-PAK1chr1177070062-0.0014935350.9985065
ENST00000330838ENST00000278568ANKRD17chr474123992-PAK1chr1177070062-0.0047339260.9952661
ENST00000330838ENST00000528203ANKRD17chr474123992-PAK1chr1177070062-0.0053957980.9946042

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 ANKRD17-PAK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ANKRD17chr474123992PAK1chr1177070062510133EEDDDDEEEEVSENVKAVSETPAVPP
ANKRD17chr474123992PAK1chr1177070062523133EEDDDDEEEEVSENVKAVSETPAVPP

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Potential FusionNeoAntigen Information of ANKRD17-PAK1 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.
ANKRD17-PAK1_74123992_77070062.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)
ANKRD17-PAK1chr474123992chr1177070062523HLA-B45:01EEVSENVKA0.99750.7777817
ANKRD17-PAK1chr474123992chr1177070062523HLA-B45:01EEEEVSENV0.99440.9257615
ANKRD17-PAK1chr474123992chr1177070062523HLA-B50:02EEVSENVKA0.9930.5409817
ANKRD17-PAK1chr474123992chr1177070062523HLA-B50:02EEEEVSENV0.97060.7046615
ANKRD17-PAK1chr474123992chr1177070062523HLA-B50:01EEVSENVKA0.4840.6899817
ANKRD17-PAK1chr474123992chr1177070062523HLA-B41:01EEVSENVKA0.36220.7598817
ANKRD17-PAK1chr474123992chr1177070062523HLA-B45:01EEVSENVKAV0.99630.8333818
ANKRD17-PAK1chr474123992chr1177070062523HLA-B45:01EEEVSENVKA0.97740.806717
ANKRD17-PAK1chr474123992chr1177070062523HLA-B50:02EEEVSENVKA0.93870.617717
ANKRD17-PAK1chr474123992chr1177070062523HLA-B45:01EEEEVSENVKA0.99960.8681617
ANKRD17-PAK1chr474123992chr1177070062523HLA-B45:01SENVKAVSETP0.99950.89581122
ANKRD17-PAK1chr474123992chr1177070062523HLA-B40:06EEVSENVKA0.98440.5541817
ANKRD17-PAK1chr474123992chr1177070062523HLA-B44:10EEEEVSENV0.83020.5171615
ANKRD17-PAK1chr474123992chr1177070062523HLA-A68:02EVSENVKAV0.99740.5844918
ANKRD17-PAK1chr474123992chr1177070062523HLA-A25:01EVSENVKAV0.99440.8629918
ANKRD17-PAK1chr474123992chr1177070062523HLA-A69:01EVSENVKAV0.99090.7139918
ANKRD17-PAK1chr474123992chr1177070062523HLA-B50:04EEVSENVKA0.4840.6899817
ANKRD17-PAK1chr474123992chr1177070062523HLA-B50:05EEVSENVKA0.4840.6899817
ANKRD17-PAK1chr474123992chr1177070062523HLA-A68:02EEVSENVKAV0.84730.6958818

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Potential FusionNeoAntigen Information of ANKRD17-PAK1 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.
ANKRD17-PAK1_74123992_77070062.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)
ANKRD17-PAK1chr474123992chr1177070062523DRB1-0324EEEVSENVKAVSETP722
ANKRD17-PAK1chr474123992chr1177070062523DRB1-0906SENVKAVSETPAVPP1126
ANKRD17-PAK1chr474123992chr1177070062523DRB1-1503SENVKAVSETPAVPP1126
ANKRD17-PAK1chr474123992chr1177070062523DRB1-1503VSENVKAVSETPAVP1025
ANKRD17-PAK1chr474123992chr1177070062523DRB1-1523SENVKAVSETPAVPP1126
ANKRD17-PAK1chr474123992chr1177070062523DRB1-1523VSENVKAVSETPAVP1025

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Fusion breakpoint peptide structures of ANKRD17-PAK1

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
1647EEEEVSENVKAVSEANKRD17PAK1chr474123992chr1177070062523

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ANKRD17-PAK1

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-B14:023BVN1647EEEEVSENVKAVSE-7.9962-8.1096
HLA-B14:023BVN1647EEEEVSENVKAVSE-5.70842-6.74372
HLA-B52:013W391647EEEEVSENVKAVSE-6.83737-6.95077
HLA-B52:013W391647EEEEVSENVKAVSE-4.4836-5.5189
HLA-A11:014UQ21647EEEEVSENVKAVSE-10.0067-10.1201
HLA-A11:014UQ21647EEEEVSENVKAVSE-9.03915-10.0745
HLA-A24:025HGA1647EEEEVSENVKAVSE-6.56204-6.67544
HLA-A24:025HGA1647EEEEVSENVKAVSE-5.42271-6.45801
HLA-B44:053DX81647EEEEVSENVKAVSE-7.85648-8.89178
HLA-B44:053DX81647EEEEVSENVKAVSE-5.3978-5.5112
HLA-A02:016TDR1647EEEEVSENVKAVSE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ANKRD17-PAK1

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
ANKRD17-PAK1chr474123992chr11770700621122SENVKAVSETPTCTGAGAATGTGAAGGCTGTGTCTGAGACTCCT
ANKRD17-PAK1chr474123992chr1177070062615EEEEVSENVGAGGAAGAGGAGGTTTCTGAGAATGTG
ANKRD17-PAK1chr474123992chr1177070062617EEEEVSENVKAGAGGAAGAGGAGGTTTCTGAGAATGTGAAGGCT
ANKRD17-PAK1chr474123992chr1177070062717EEEVSENVKAGAAGAGGAGGTTTCTGAGAATGTGAAGGCT
ANKRD17-PAK1chr474123992chr1177070062817EEVSENVKAGAGGAGGTTTCTGAGAATGTGAAGGCT
ANKRD17-PAK1chr474123992chr1177070062818EEVSENVKAVGAGGAGGTTTCTGAGAATGTGAAGGCTGTG
ANKRD17-PAK1chr474123992chr1177070062918EVSENVKAVGAGGTTTCTGAGAATGTGAAGGCTGTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ANKRD17-PAK1chr474123992chr11770700621025VSENVKAVSETPAVPGTTTCTGAGAATGTGAAGGCTGTGTCTGAGACTCCTGCAGTGCCA
ANKRD17-PAK1chr474123992chr11770700621126SENVKAVSETPAVPPTCTGAGAATGTGAAGGCTGTGTCTGAGACTCCTGCAGTGCCACCA
ANKRD17-PAK1chr474123992chr1177070062722EEEVSENVKAVSETPGAAGAGGAGGTTTCTGAGAATGTGAAGGCTGTGTCTGAGACTCCT

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Information of the samples that have these potential fusion neoantigens of ANKRD17-PAK1

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
UCECANKRD17-PAK1chr474123992ENST00000330838chr1177070062ENST00000278568TCGA-D1-A17C

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Potential target of CAR-T therapy development for ANKRD17-PAK1

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 ANKRD17-PAK1

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 ANKRD17-PAK1

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