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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:TWF1_IRAK4

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: TWF1_IRAK4
KinaseFusionDB ID: KFG6921
FusionGDB2.0 ID: KFG6921
HgeneTgene
Gene symbol

TWF1

IRAK4

Gene ID

5756

51135

Gene nametwinfilin actin binding protein 1interleukin 1 receptor associated kinase 4
SynonymsA6|PTK9IMD67|IPD1|IRAK-4|NY-REN-64|REN64
Cytomap

12q12

12q12

Type of geneprotein-codingprotein-coding
Descriptiontwinfilin-1A6 protein tyrosine kinasePTK9 protein tyrosine kinase 9protein A6protein tyrosine kinase 9twinfilin, actin-binding protein, homolog 1interleukin-1 receptor-associated kinase 4renal carcinoma antigen NY-REN-64
Modification date2024040720240403
UniProtAcc

Q12792

Q9NWZ3

Ensembl transtripts involved in fusion geneENST idsENST00000552521, ENST00000325127, 
ENST00000395510, ENST00000547564, 
ENST00000548315, 		ENST00000431837, 
ENST00000440781, ENST00000448290, 
ENST00000551736, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: TWF1 [Title/Abstract] AND IRAK4 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TWF1(44196089)-IRAK4(44180202), # 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
HgeneTWF1

GO:0043538

regulation of actin phosphorylation

10406962

TgeneIRAK4

GO:0038172

interleukin-33-mediated signaling pathway

11960013

TgeneIRAK4

GO:0070498

interleukin-1-mediated signaling pathway

20485341


check buttonKinase Fusion gene breakpoints across TWF1 (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 buttonKinase Fusion gene breakpoints across IRAK4 (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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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-BR-8296-01ATWF1chr12

44196089

IRAK4chr12

44180202



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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/chr12:44196089/chr12:44180202)
- 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
TWF1

Q12792

IRAK4

Q9NWZ3

FUNCTION: Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles (By similarity). {ECO:0000250}.FUNCTION: Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}.

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 TWF1_IRAK4


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
IRAK4Q9NWZ3humanPELI1Q96FA3T80DQHsIsYtLsRAQtVPellino
IRAK4Q9NWZ3humanNCF1P14598S348PGPQsPGsPLEEERQ
IRAK4Q9NWZ3humanIRAK4Q9NWZ3T345kFAQtVMtsRIVGTtPK_Tyr_Ser-Thr
IRAK4Q9NWZ3humanPELI1Q96FA3T288QCPVGFNtLAFPsMkPellino
IRAK4Q9NWZ3humanPELI1Q96FA3T127GSQSNsDtQSVQSTIPellino
IRAK4Q9NWZ3humanNCF1P14598T356PLEEERQtQRsKPQP
IRAK4Q9NWZ3humanNCF1P14598S320QRsRKRLsQDAYRRNNECFESHC
IRAK4Q9NWZ3humanIRAK1P51617S376GSsPsQssMVARtQTPkinase
IRAK4Q9NWZ3humanIRAK4Q9NWZ3T209KGYVNNttVAVKKLAPK_Tyr_Ser-Thr
IRAK4Q9NWZ3humanIRAK4Q9NWZ3S8MNkPItPsTYVRCLN
IRAK4Q9NWZ3humanIRAK4Q9NWZ3S346FAQtVMtsRIVGTtAPK_Tyr_Ser-Thr
IRAK4Q9NWZ3humanNCF1P14598S370PAVPPRPsADLILNRp47_phox_C
IRAK4Q9NWZ3humanPELI1Q96FA3S82HsIsYtLsRAQtVVVPellino
IRAK4Q9NWZ3humanIRAK4Q9NWZ3T342AsEkFAQtVMtsRIVPK_Tyr_Ser-Thr
IRAK4Q9NWZ3humanIRAK4Q9NWZ3T352tsRIVGTtAYMAPEAPK_Tyr_Ser-Thr
IRAK4Q9NWZ3humanPELI1Q96FA3S70PQAAKAIsNKDQHsIPellino
IRAK4Q9NWZ3humanNCF1P14598S288QKsGQDVsQAQRQIKNECFESHC
IRAK4Q9NWZ3humanNCF1P14598T153KSTATDItGPIILQT
IRAK4Q9NWZ3humanIRAK1P51617T387RtQTVRGtLAYLPEEPkinase
IRAK4Q9NWZ3humanIRAK4Q9NWZ3T208YKGYVNNttVAVKKLPK_Tyr_Ser-Thr
IRAK4Q9NWZ3humanPELI1Q96FA3S78NKDQHsIsYtLsRAQPellino
IRAK4Q9NWZ3humanPELI1Q96FA3T86YtLsRAQtVVVEYTHPellino
IRAK4Q9NWZ3humanNCF1P14598S345QARPGPQsPGsPLEE
IRAK4Q9NWZ3humanNCF1P14598T133KLPTDNQtKKPEtyL
IRAK4Q9NWZ3humanNCF1P14598T138NQtKKPEtyLMPKDG
IRAK4Q9NWZ3humanIRAK4Q9NWZ3T6__MNkPItPsTYVRC
IRAK4Q9NWZ3humanIRAK4Q9NWZ3S151SYMPPDsssPENKsL
IRAK4Q9NWZ3humanPELI1Q96FA3S293FNtLAFPsMkRkDVVPellino
IRAK4Q9NWZ3humanIRAK4Q9NWZ3S152YMPPDsssPENKsLE
IRAK4Q9NWZ3humanIRAK4Q9NWZ3S114KTANTLPskEAITVQ
IRAK4Q9NWZ3humanPELI1Q96FA3S76IsNKDQHsIsYtLsRPellino
IRAK4Q9NWZ3humanIRAK4Q9NWZ3S150QSYMPPDsssPENKs
IRAK4Q9NWZ3humanNCF1P14598S359EERQtQRsKPQPAVPp47_phox_C


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
IRAK4IDDescription0.00e+00
IRAK4GO:0008063Toll signaling pathway1.26e-07
IRAK4GO:0140894endolysosomal toll-like receptor signaling pathway5.39e-06
IRAK4GO:0034142toll-like receptor 4 signaling pathway6.64e-06
IRAK4GO:0140895cell surface toll-like receptor signaling pathway7.54e-06
IRAK4GO:0002752cell surface pattern recognition receptor signaling pathway8.31e-06
IRAK4GO:0045088regulation of innate immune response9.01e-06
IRAK4GO:0002220innate immune response activating cell surface receptor signaling pathway1.32e-05
IRAK4GO:0002753cytosolic pattern recognition receptor signaling pathway4.81e-05
IRAK4GO:0007254JNK cascade5.95e-05
IRAK4GO:0043123positive regulation of canonical NF-kappaB signal transduction9.33e-05
IRAK4GO:0034162toll-like receptor 9 signaling pathway1.11e-04
IRAK4GO:0002755MyD88-dependent toll-like receptor signaling pathway1.11e-04
IRAK4GO:0051403stress-activated MAPK cascade1.11e-04
IRAK4GO:0002221pattern recognition receptor signaling pathway1.11e-04
IRAK4GO:0031098stress-activated protein kinase signaling cascade1.11e-04
IRAK4GO:0002758innate immune response-activating signaling pathway1.29e-04
IRAK4GO:0043122regulation of canonical NF-kappaB signal transduction1.36e-04
IRAK4GO:0002218activation of innate immune response1.45e-04
IRAK4GO:0007249canonical NF-kappaB signal transduction1.76e-04
IRAK4GO:0070498interleukin-1-mediated signaling pathway1.78e-04
IRAK4GO:0002429immune response-activating cell surface receptor signaling pathway1.90e-04
IRAK4GO:0045089positive regulation of innate immune response2.18e-04
IRAK4GO:0002768immune response-regulating cell surface receptor signaling pathway2.18e-04
IRAK4GO:0032496response to lipopolysaccharide2.18e-04
IRAK4GO:0030522intracellular receptor signaling pathway2.18e-04
IRAK4GO:0002237response to molecule of bacterial origin2.31e-04
IRAK4GO:0002833positive regulation of response to biotic stimulus2.31e-04
IRAK4GO:0002757immune response-activating signaling pathway4.67e-04
IRAK4GO:0031349positive regulation of defense response4.72e-04
IRAK4GO:0002764immune response-regulating signaling pathway5.15e-04
IRAK4GO:0002224toll-like receptor signaling pathway6.22e-04
IRAK4GO:0048661positive regulation of smooth muscle cell proliferation1.06e-03
IRAK4GO:0071347cellular response to interleukin-11.32e-03
IRAK4GO:0070555response to interleukin-12.03e-03
IRAK4GO:0048660regulation of smooth muscle cell proliferation2.95e-03
IRAK4GO:0048659smooth muscle cell proliferation3.00e-03
IRAK4GO:0071222cellular response to lipopolysaccharide4.86e-03
IRAK4GO:0071219cellular response to molecule of bacterial origin5.28e-03
IRAK4GO:0033002muscle cell proliferation5.50e-03
IRAK4GO:0071216cellular response to biotic stimulus6.16e-03
IRAK4GO:0045860positive regulation of protein kinase activity6.80e-03
IRAK4GO:0033674positive regulation of kinase activity9.45e-03
IRAK4GO:0034139regulation of toll-like receptor 3 signaling pathway1.15e-02
IRAK4GO:1903037regulation of leukocyte cell-cell adhesion1.16e-02
IRAK4GO:0071394cellular response to testosterone stimulus1.20e-02
IRAK4GO:0034145positive regulation of toll-like receptor 4 signaling pathway1.27e-02
IRAK4GO:0051347positive regulation of transferase activity1.27e-02
IRAK4GO:0007159leukocyte cell-cell adhesion1.27e-02
IRAK4GO:0002679respiratory burst involved in defense response1.44e-02

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Related Drugs to TWF1_IRAK4


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 TWF1-IRAK4 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 TWF1_IRAK4


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