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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

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pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:ADD1_GRK4

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: ADD1_GRK4
KinaseFusionDB ID: KFG187
FusionGDB2.0 ID: KFG187
HgeneTgene
Gene symbol

ADD1

GRK4

Gene ID

118

2868

Gene nameadducin 1G protein-coupled receptor kinase 4
SynonymsADDAGPRK2L|GPRK4|GRK4a|IT11
Cytomap

4p16.3

4p16.3

Type of geneprotein-codingprotein-coding
Descriptionalpha-adducinadducin 1 (alpha)alpha-adducin 1erythrocyte adducin alpha subunitG protein-coupled receptor kinase 4G protein-coupled receptor kinase 2-like
Modification date2024040720240411
UniProtAcc

P35611

P32298

Ensembl transtripts involved in fusion geneENST idsENST00000264758, ENST00000355842, 
ENST00000398123, ENST00000398125, 
ENST00000398129, ENST00000446856, 
ENST00000503455, ENST00000513328, 
ENST00000538860, 
ENST00000442472, 
ENST00000503518, ENST00000509545, 
ENST00000345167, ENST00000398051, 
ENST00000398052, ENST00000504933, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: ADD1 [Title/Abstract] AND GRK4 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADD1(2916767)-GRK4(3021367), # samples:1
GRK4(2988522)-ADD1(2922961), # samples:1
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneADD1

GO:0032092

positive regulation of protein binding

3693401|7642559

HgeneADD1

GO:0051016

barbed-end actin filament capping

8626479

HgeneADD1

GO:0051017

actin filament bundle assembly

3693401

HgeneADD1

GO:0071277

cellular response to calcium ion

25978380

HgeneADD1

GO:1903142

positive regulation of establishment of endothelial barrier

25978380

HgeneADD1

GO:1903393

positive regulation of adherens junction organization

25978380

TgeneGRK4

GO:0031623

receptor internalization

20074556


check buttonKinase Fusion gene breakpoints across ADD1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonKinase Fusion gene breakpoints across GRK4 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.


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Kinase Fusion Gene Sample Information

check buttonKinase Fusion gene information.
check button Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceSampleHgeneHchrHbpTgeneTchrTbp
ChimerDB4TCGA-LN-A49LADD1chr4

2916767

GRK4chr4

3021367



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Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(amino acids)

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Kinase Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq

Multiple Sequence Alignment of All Fusion Protein Isoforms



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Kinase Fusion Protein Functional Features


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/:2916767/:3021367)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
ADD1

P35611

GRK4

P32298

FUNCTION: Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin.FUNCTION: Specifically phosphorylates the activated forms of G protein-coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its activity is inhibited by calmodulin; the other three isoforms do not phosphorylate rhodopsin and do not interact with calmodulin. GRK4-alpha and GRK4-gamma phosphorylate DRD3. Phosphorylates ADRB2. {ECO:0000269|PubMed:19520868, ECO:0000269|PubMed:8626439}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


check button - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


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Kinase-Substrate Information of ADD1_GRK4


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
GRK4P32298humanGRK4P32298S10LENIVANsLLLkARQ
GRK4P32298humanGRK4P32298S430MLLtKNPsKRLGCRGPkinase
GRK4P32298humanBDKRB2P30411S366EPIQMENsMGTLRTs
GRK4P32298humanBDKRB2P30411S375GTLRTsIsVERQIHk
GRK4P32298humanGRK4P32298S419KFSEDAKsICRMLLtPkinase
GRK4P32298humanGRK4P32298S139GLKEENPsKKAFEECRGS
GRK4P32298humanGRK4P32298T426sICRMLLtKNPsKRLPkinase
GRK4P32298humanGRK4P32298S249VQsRFVVsLAYAYEtPkinase
GRK4P32298humanGRK4P32298S244RILEKVQsRFVVsLAPkinase
GRK4P32298humanBDKRB2P30411S373sMGTLRTsIsVERQI
GRK4P32298humanGRK4P32298S485VLDIEQFsVVKGIYL
GRK4P32298humanGRK4P32298T256sLAYAYEtKDALCLVPkinase


check button Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust
GRK4escriptio0.00e+00
GRK4O:007121ellular response to abiotic stimulu1.06e-02
GRK4O:010400ellular response to environmental stimulu1.06e-02
GRK4O:000862ntrinsic apoptotic signaling pathway in response to osmotic stres1.65e-02
GRK4O:002240egulation of rhodopsin mediated signaling pathwa1.65e-02
GRK4O:010604egulation of cellular response to osmotic stres1.65e-02
GRK4O:001605hodopsin mediated signaling pathwa1.65e-02
GRK4O:004748egulation of response to osmotic stres1.65e-02
GRK4O:000760phototransductio2.12e-03
GRK4O:000965esponse to salt stres1.68e-02
GRK4O:003313egative regulation of peptidyl-serine phosphorylatio1.68e-02
GRK4O:005048rachidonic acid secretio1.68e-02
GRK4O:190396rachidonate transpor1.68e-02
GRK4O:190179egative regulation of signal transduction by p53 class mediato1.68e-02
GRK4O:190225egulation of intrinsic apoptotic signaling pathway by p53 class mediato1.68e-02
GRK4O:003230cosanoid secretio1.82e-02
GRK4O:004231asodilatio1.82e-02
GRK4O:000760hototransductio1.82e-02
GRK4O:004311egulation of vascular permeabilit1.82e-02
GRK4O:007147ellular response to osmotic stres1.82e-02
GRK4O:000958etection of visible ligh1.82e-02
GRK4O:007171cosanoid transpor1.99e-02
GRK4O:001922egulation of vasoconstrictio1.99e-02
GRK4O:001590ong-chain fatty acid transpor1.99e-02
GRK4O:000958etection of light stimulu1.99e-02
GRK4O:000697esponse to osmotic stres2.16e-02
GRK4O:004231asoconstrictio2.16e-02
GRK4O:007233ntrinsic apoptotic signaling pathway by p53 class mediato2.16e-02
GRK4O:190179egulation of signal transduction by p53 class mediato2.57e-02
GRK4O:000693mooth muscle contractio2.57e-02
GRK4O:200124egative regulation of intrinsic apoptotic signaling pathwa2.57e-02
GRK4O:001590atty acid transpor2.57e-02
GRK4O:007148ellular response to light stimulu2.57e-02
GRK4O:003162eceptor internalizatio2.57e-02
GRK4O:000958etection of external stimulu2.57e-02
GRK4O:003313egulation of peptidyl-serine phosphorylatio2.57e-02
GRK4O:000827egulation of G protein-coupled receptor signaling pathwa2.57e-02
GRK4O:000958etection of abiotic stimulu2.57e-02
GRK4O:003529egulation of tube diamete2.57e-02
GRK4O:009774lood vessel diameter maintenanc2.57e-02
GRK4O:003515egulation of tube siz2.57e-02
GRK4O:000720ositive regulation of cytosolic calcium ion concentratio2.89e-02
GRK4O:007233ignal transduction by p53 class mediato2.89e-02
GRK4O:001571onocarboxylic acid transpor2.89e-02
GRK4O:007147ellular response to radiatio2.89e-02
GRK4O:200124egulation of intrinsic apoptotic signaling pathwa2.96e-02
GRK4O:200123egative regulation of apoptotic signaling pathwa3.70e-02
GRK4O:000689eceptor-mediated endocytosi3.77e-02
GRK4O:190352egulation of blood circulatio3.77e-02
GRK4O:000301ascular process in circulatory syste3.85e-02

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Related Drugs to ADD1_GRK4


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

check button Distribution of the number of studies mentioning ADD1-GRK4 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title

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Related Diseases to ADD1_GRK4


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)
MeSH IDMeSH term

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource


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Clinical Trials of the Found Drugs/Small Molecules


check button Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

check button Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate