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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:ADRBK1-IQGAP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADRBK1-IQGAP1
FusionPDB ID: 2538
FusionGDB2.0 ID: 34863
HgeneTgene
Gene symbol

ADRBK1

IQGAP1

Gene ID

156

8826

Gene nameG protein-coupled receptor kinase 2IQ motif containing GTPase activating protein 1
SynonymsADRBK1|BARK1|BETA-ARK1HUMORFA01|SAR1|p195
Cytomap

11q13.2

15q26.1

Type of geneprotein-codingprotein-coding
Descriptionbeta-adrenergic receptor kinase 1adrenergic beta receptor kinase 1beta-ARK-1ras GTPase-activating-like protein IQGAP1RasGAP-like with IQ motifs
Modification date2020031320200327
UniProtAcc.

P46940

Main function of 5'-partner protein: FUNCTION: Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Binds to activated CDC42 but does not stimulate its GTPase activity. It associates with calmodulin. Could serve as an assembly scaffold for the organization of a multimolecular complex that would interface incoming signals to the reorganization of the actin cytoskeleton at the plasma membrane. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}.
Ensembl transtripts involved in fusion geneENST idsENST00000308595, ENST00000526285, 
ENST00000527176, 
ENST00000560020, 
ENST00000560738, ENST00000268182, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 3 X 5=13517 X 15 X 7=1785
# samples 919
** MAII scorelog2(9/135*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/1785*10)=-3.23185275058551
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ADRBK1 [Title/Abstract] AND IQGAP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADRBK1 [Title/Abstract] AND IQGAP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADRBK1(67034283)-IQGAP1(90969342), # samples:1
Anticipated loss of major functional domain due to fusion event.ADRBK1-IQGAP1 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.
ADRBK1-IQGAP1 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.
ADRBK1-IQGAP1 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.
ADRBK1-IQGAP1 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
HgeneADRBK1

GO:0007217

tachykinin receptor signaling pathway

17986524

HgeneADRBK1

GO:0031623

receptor internalization

20074556

TgeneIQGAP1

GO:0071277

cellular response to calcium ion

18567582



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/chr11:67034283/chr15:90969342)
- 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 ADRBK1 (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 IQGAP1 (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)
ENST00000308595ADRBK1chr1167034283-ENST00000268182IQGAP1chr1590969342+735740329052211643
ENST00000526285ADRBK1chr1167034283-ENST00000268182IQGAP1chr1590969342+728633221951501643

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
ENST00000308595ENST00000268182ADRBK1chr1167034283-IQGAP1chr1590969342+0.0005015540.9994985
ENST00000526285ENST00000268182ADRBK1chr1167034283-IQGAP1chr1590969342+0.0004497530.9995503

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 ADRBK1-IQGAP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADRBK1chr1167034283IQGAP1chr159096934233237AARASKKILLPEPRWMEACLGEDLPP
ADRBK1chr1167034283IQGAP1chr159096934240337AARASKKILLPEPRWMEACLGEDLPP

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Potential FusionNeoAntigen Information of ADRBK1-IQGAP1 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.
ADRBK1-IQGAP1_67034283_90969342.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)
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B57:01KILLPEPRW0.99770.9918615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B56:01LPEPRWMEA0.99340.8079918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B58:01KILLPEPRW0.99260.9826615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B58:02KILLPEPRW0.99260.9727615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A31:08KILLPEPRW0.98240.522615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B08:09LPEPRWMEA0.9730.9241918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B55:01LPEPRWMEA0.96550.5766918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B57:03KILLPEPRW0.96510.9954615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B15:17KILLPEPRW0.92070.9442615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A32:13KILLPEPRW0.91930.9916615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A02:04ILLPEPRWM0.89320.9186716
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A02:17ILLPEPRWM0.89170.8264716
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B15:16KILLPEPRW0.88860.9213615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B82:01LPEPRWMEA0.42050.6685918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B57:01KKILLPEPRW0.99560.9889515
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B58:01KKILLPEPRW0.95920.9739515
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A02:67ILLPEPRWMEA0.98860.6615718
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A02:24ILLPEPRWMEA0.98860.6615718
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A02:30ILLPEPRWMEA0.98860.6615718
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A02:60ILLPEPRWMEA0.98840.7004718
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A02:29ILLPEPRWMEA0.97710.6614718
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A02:20ILLPEPRWMEA0.9550.6694718
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-C01:17LLPEPRWM0.96050.9725816
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-C01:30LLPEPRWM0.95960.9748816
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B54:01LPEPRWMEA0.99840.9316918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B42:02LPEPRWMEA0.98490.7546918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B42:01LPEPRWMEA0.97630.7426918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B78:01LPEPRWMEA0.95050.8873918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B56:04LPEPRWMEA0.940.7989918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B42:02EPRWMEACL0.70220.54571120
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B42:01EPRWMEACL0.64850.52981120
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B39:10LPEPRWMEA0.41660.9794918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A02:01ILLPEPRWMEA0.98860.6615718
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-C01:02LLPEPRWM0.97010.9717816
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B57:10KILLPEPRW0.99770.9918615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B55:02LPEPRWMEA0.98990.8614918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-A32:01KILLPEPRW0.98970.9915615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B56:05LPEPRWMEA0.98110.858918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B57:04KILLPEPRW0.98010.707615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B58:06KILLPEPRW0.97740.9272615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B59:01LPEPRWMEA0.96250.9918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B56:02LPEPRWMEA0.940.7989918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B78:02LPEPRWMEA0.92480.9144918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B55:04LPEPRWMEA0.89010.8049918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B57:02KILLPEPRW0.74640.9351615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B67:01LPEPRWMEA0.60620.9737918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B15:24KILLPEPRW0.4550.964615
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B82:02LPEPRWMEA0.42050.6685918
ADRBK1-IQGAP1chr1167034283chr1590969342403HLA-B57:10KKILLPEPRW0.99560.9889515

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Potential FusionNeoAntigen Information of ADRBK1-IQGAP1 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 ADRBK1-IQGAP1

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
4305KILLPEPRWMEACLADRBK1IQGAP1chr1167034283chr1590969342403

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADRBK1-IQGAP1

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-B14:023BVN4305KILLPEPRWMEACL-7.9962-8.1096
HLA-B14:023BVN4305KILLPEPRWMEACL-5.70842-6.74372
HLA-B52:013W394305KILLPEPRWMEACL-6.83737-6.95077
HLA-B52:013W394305KILLPEPRWMEACL-4.4836-5.5189
HLA-A11:014UQ24305KILLPEPRWMEACL-10.0067-10.1201
HLA-A11:014UQ24305KILLPEPRWMEACL-9.03915-10.0745
HLA-A24:025HGA4305KILLPEPRWMEACL-6.56204-6.67544
HLA-A24:025HGA4305KILLPEPRWMEACL-5.42271-6.45801
HLA-B44:053DX84305KILLPEPRWMEACL-7.85648-8.89178
HLA-B44:053DX84305KILLPEPRWMEACL-5.3978-5.5112
HLA-A02:016TDR4305KILLPEPRWMEACL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ADRBK1-IQGAP1

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
ADRBK1-IQGAP1chr1167034283chr15909693421120EPRWMEACLGCCCAGGTGGATGGAAGCATGCCTAGG
ADRBK1-IQGAP1chr1167034283chr1590969342515KKILLPEPRWGAAGATCCTGCTGCCCGAGCCCAGGTGGAT
ADRBK1-IQGAP1chr1167034283chr1590969342615KILLPEPRWGATCCTGCTGCCCGAGCCCAGGTGGAT
ADRBK1-IQGAP1chr1167034283chr1590969342716ILLPEPRWMCCTGCTGCCCGAGCCCAGGTGGATGGA
ADRBK1-IQGAP1chr1167034283chr1590969342718ILLPEPRWMEACCTGCTGCCCGAGCCCAGGTGGATGGAAGCATG
ADRBK1-IQGAP1chr1167034283chr1590969342816LLPEPRWMGCTGCCCGAGCCCAGGTGGATGGA
ADRBK1-IQGAP1chr1167034283chr1590969342918LPEPRWMEAGCCCGAGCCCAGGTGGATGGAAGCATG

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 ADRBK1-IQGAP1

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
BRCAADRBK1-IQGAP1chr1167034283ENST00000308595chr1590969342ENST00000268182TCGA-AR-A0TS-01A

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Potential target of CAR-T therapy development for ADRBK1-IQGAP1

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 ADRBK1-IQGAP1

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 ADRBK1-IQGAP1

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