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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:CTNND2_NRBP1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: CTNND2_NRBP1
KinaseFusionDB ID: KFG1564
FusionGDB2.0 ID: KFG1564
HgeneTgene
Gene symbol

CTNND2

NRBP1

Gene ID

1501

29959

Gene namecatenin delta 2nuclear receptor binding protein 1
SynonymsGT24|NPRAPBCON3|MADM|MUDPNP|NRBP
Cytomap

5p15.2

2p23.3

Type of geneprotein-codingprotein-coding
Descriptioncatenin delta-2T-cell delta-catenincatenin (cadherin-associated protein), delta 2 (neural plakophilin-related arm-repeat protein)neurojunginnuclear receptor-binding proteinmultiple domain putative nuclear proteinmyeloid leukemia factor 1 adaptor molecule
Modification date2024040720240403
UniProtAcc

Q9UQB3

Q9UHY1

Ensembl transtripts involved in fusion geneENST idsENST00000458100, ENST00000304623, 
ENST00000359640, ENST00000495388, 
ENST00000503622, ENST00000511377, 
ENST00000233557, ENST00000379852, 
ENST00000379863, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: CTNND2 [Title/Abstract] AND NRBP1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CTNND2(11732248)-NRBP1(27656540), # samples:3
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
TgeneNRBP1

GO:0006888

endoplasmic reticulum to Golgi vesicle-mediated transport

11956649


check buttonKinase Fusion gene breakpoints across CTNND2 (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 NRBP1 (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-QH-A6XC-01ACTNND2chr5

11732248

NRBP1chr2

27656540

ChimerDB4TCGA-QH-A6XCCTNND2chr5

11732247

NRBP1chr2

27656539



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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)
ENST00000304623ENST00000233557CTNND2chr511732248NRBP1chr2276565402209523
ENST00000304623ENST00000233557CTNND2chr511732247NRBP1chr2276565392209523

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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

>ENST00000304623_ENST00000233557_CTNND2_chr5_11732248_NRBP1_chr2_27656540_length(amino acids)=523
MFARKPPGAAPLGAMPVPDQPSSASEKTSSLSPGLNTSNGDGSETETTSAILASVKEQVNQRNVPGIDSAYLAMDTEEGVEVVWNEVQFS
ERKNYKLQEEKVRAVFDNLIQLEHLNIVKFHKYWADIKENKARVIFITEYMSSGSLKQFLKKTKKNHKTMNEKAWKRWCTQILSALSYLH
SCDPPIIHGNLTCDTIFIQHNGLIKIGSVAPDTINNHVKTCREEQKNLHFFAPEYGEVTNVTTAVDIYSFGMCALEMAVLEIQGNGESSY
VPQEAISSAIQLLEDPLQREFIQKCLQSEPARRPTARELLFHPALFEVPSLKLLAAHCIVGHQHMIPENALEEITKNMDTSAVLAEIPAG
PGREPVQTLYSQSPALELDKFLEDVRNGIYPLTAFGLPRPQQPQQEEVTSPVVPPSVKTPTPEPAEVETRKVVLMQCNIESVEEGVKHHL

--------------------------------------------------------------

>ENST00000304623_ENST00000233557_CTNND2_chr5_11732247_NRBP1_chr2_27656539_length(amino acids)=523
MFARKPPGAAPLGAMPVPDQPSSASEKTSSLSPGLNTSNGDGSETETTSAILASVKEQVNQRNVPGIDSAYLAMDTEEGVEVVWNEVQFS
ERKNYKLQEEKVRAVFDNLIQLEHLNIVKFHKYWADIKENKARVIFITEYMSSGSLKQFLKKTKKNHKTMNEKAWKRWCTQILSALSYLH
SCDPPIIHGNLTCDTIFIQHNGLIKIGSVAPDTINNHVKTCREEQKNLHFFAPEYGEVTNVTTAVDIYSFGMCALEMAVLEIQGNGESSY
VPQEAISSAIQLLEDPLQREFIQKCLQSEPARRPTARELLFHPALFEVPSLKLLAAHCIVGHQHMIPENALEEITKNMDTSAVLAEIPAG
PGREPVQTLYSQSPALELDKFLEDVRNGIYPLTAFGLPRPQQPQQEEVTSPVVPPSVKTPTPEPAEVETRKVVLMQCNIESVEEGVKHHL

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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/chr5:11732248/chr2:27656540)
- 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
CTNND2

Q9UQB3

NRBP1

Q9UHY1

FUNCTION: Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses (PubMed:25807484). Involved in the regulation of Wnt signaling (PubMed:25807484). It probably acts on beta-catenin turnover, facilitating beta-catenin interaction with GSK3B, phosphorylation, ubiquitination and degradation (By similarity). Functions as a transcriptional activator when bound to ZBTB33 (By similarity). May be involved in neuronal cell adhesion and tissue morphogenesis and integrity by regulating adhesion molecules. {ECO:0000250|UniProtKB:O35927, ECO:0000269|PubMed:25807484, ECO:0000269|PubMed:9971746}.FUNCTION: Required for embryonic development (By similarity). Plays a role in intestinal epithelial cell fate and proliferation, thereby involved in the architectural development of the intestine potentially via the regulation of Wnt-responsive genes (By similarity). May play a role in subcellular trafficking between the endoplasmic reticulum and Golgi apparatus through interactions with the Rho-type GTPases (PubMed:11956649). Binding to the NS3 protein of dengue virus type 2 appears to subvert this activity into the alteration of the intracellular membrane structure associated with flaviviral replication (PubMed:15084397). {ECO:0000250|UniProtKB:Q99J45, ECO:0000269|PubMed:11956649, ECO:0000269|PubMed:15084397}.

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
TgeneCTNND211732247NRBP127656539ENST0000030462311868_32770536DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneCTNND211732247NRBP127656539ENST0000030462321968_32770536DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneCTNND211732248NRBP127656540ENST0000030462311868_32770536DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
TgeneCTNND211732248NRBP127656540ENST0000030462321968_32770536DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159


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Kinase Fusion Protein Structures

check button CIF files of the predicted kinase fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB)HenstTenstHgeneHchrHbpTgeneTchrTbpAA seqLen(AA seq)
PDB file >>>131_CTNND2_NRBP1ENST00000304623ENST00000233557CTNND2chr511732247NRBP1chr227656539
MFARKPPGAAPLGAMPVPDQPSSASEKTSSLSPGLNTSNGDGSETETTSAILASVKEQVNQRNVPGIDSAYLAMDTEEGVEVVWNEVQFS
ERKNYKLQEEKVRAVFDNLIQLEHLNIVKFHKYWADIKENKARVIFITEYMSSGSLKQFLKKTKKNHKTMNEKAWKRWCTQILSALSYLH
SCDPPIIHGNLTCDTIFIQHNGLIKIGSVAPDTINNHVKTCREEQKNLHFFAPEYGEVTNVTTAVDIYSFGMCALEMAVLEIQGNGESSY
VPQEAISSAIQLLEDPLQREFIQKCLQSEPARRPTARELLFHPALFEVPSLKLLAAHCIVGHQHMIPENALEEITKNMDTSAVLAEIPAG
PGREPVQTLYSQSPALELDKFLEDVRNGIYPLTAFGLPRPQQPQQEEVTSPVVPPSVKTPTPEPAEVETRKVVLMQCNIESVEEGVKHHL
523
3D view using mol* of 131_CTNND2_NRBP1
PDB file >>>TKFP_212_CTNND2_NRBP1ENST00000304623ENST00000233557CTNND2chr511732248NRBP1chr227656540
MFARKPPGAAPLGAMPVPDQPSSASEKTSSLSPGLNTSNGDGSETETTSAILASVKEQVNQRNVPGIDSAYLAMDTEEGVEVVWNEVQFS
ERKNYKLQEEKVRAVFDNLIQLEHLNIVKFHKYWADIKENKARVIFITEYMSSGSLKQFLKKTKKNHKTMNEKAWKRWCTQILSALSYLH
SCDPPIIHGNLTCDTIFIQHNGLIKIGSVAPDTINNHVKTCREEQKNLHFFAPEYGEVTNVTTAVDIYSFGMCALEMAVLEIQGNGESSY
VPQEAISSAIQLLEDPLQREFIQKCLQSEPARRPTARELLFHPALFEVPSLKLLAAHCIVGHQHMIPENALEEITKNMDTSAVLAEIPAG
PGREPVQTLYSQSPALELDKFLEDVRNGIYPLTAFGLPRPQQPQQEEVTSPVVPPSVKTPTPEPAEVETRKVVLMQCNIESVEEGVKHHL
523_CTNND2_NRBP1
PDB file >>>TKFP_213_CTNND2_NRBP1ENST00000304623ENST00000233557CTNND2chr511732247NRBP1chr227656539
MFARKPPGAAPLGAMPVPDQPSSASEKTSSLSPGLNTSNGDGSETETTSAILASVKEQVNQRNVPGIDSAYLAMDTEEGVEVVWNEVQFS
ERKNYKLQEEKVRAVFDNLIQLEHLNIVKFHKYWADIKENKARVIFITEYMSSGSLKQFLKKTKKNHKTMNEKAWKRWCTQILSALSYLH
SCDPPIIHGNLTCDTIFIQHNGLIKIGSVAPDTINNHVKTCREEQKNLHFFAPEYGEVTNVTTAVDIYSFGMCALEMAVLEIQGNGESSY
VPQEAISSAIQLLEDPLQREFIQKCLQSEPARRPTARELLFHPALFEVPSLKLLAAHCIVGHQHMIPENALEEITKNMDTSAVLAEIPAG
PGREPVQTLYSQSPALELDKFLEDVRNGIYPLTAFGLPRPQQPQQEEVTSPVVPPSVKTPTPEPAEVETRKVVLMQCNIESVEEGVKHHL
523_CTNND2_NRBP1


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Comparison of Fusion Protein Isoforms

check button Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.

check button Comparison of the Secondary Structures of Fusion Protein Isoforms

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

CTNND2_NRBP1 does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/131_CTNND2_NRBP1.png
check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
* The blue color at the bottom marks the best active site residues.
131_CTNND2_NRBP1.png
all structure sitemap plddt3 131_CTNND2_NRBP1.png
131_CTNND2_NRBP1.png
all structure sitemap plddt4 131_CTNND2_NRBP1.png


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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Kinase Fusion AA seq ID in KinaseFusionDBSite scoreSizeDscoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues

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Ramachandran Plot of Kinase Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

131_CTNND2_NRBP1_ramachandran.png
all structure CTNND2-NRBP1

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Virtual Screening Results


check button Distribution of the average docking score across all approved kinase inhibitors.
Distribution of the number of occurrence across all approved kinase inhibitors.
5'-kinase fusion protein case
3'-kinase fusion protein case
all structure CTNND2-NRBP1

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check button Drug information from DrugBank of the top 20 interacting small molecules.
* The detailed information of individual kinase inhibitors are available in the download page.
Fusion gene name infoDrugDocking scoreGlide g scoreGlide energy
131_CTNND2_NRBP1-DOCK_HTVS_1-001Neratinib-6.6243-6.8066-49.3863
131_CTNND2_NRBP1-DOCK_HTVS_1-001Neratinib-6.6243-6.8066-49.3863
131_CTNND2_NRBP1-DOCK_HTVS_1-001Nilotinib-6.39494-6.53454-47.4689
131_CTNND2_NRBP1-DOCK_HTVS_1-001Nilotinib-6.39494-6.53454-47.4689
131_CTNND2_NRBP1-DOCK_HTVS_1-001Sunitinib-6.36385-6.36805-44.1195
131_CTNND2_NRBP1-DOCK_HTVS_1-001Zanubrutinib-6.2173300000000005-6.2173300000000005-51.3519
131_CTNND2_NRBP1-DOCK_HTVS_1-001Futibatinib-6.05665-6.05665-39.7532
131_CTNND2_NRBP1-DOCK_HTVS_1-001Neratinib-6.02275-6.20865-49.0022
131_CTNND2_NRBP1-DOCK_HTVS_1-001Dacomitinib-5.91228-6.02128-42.3497
131_CTNND2_NRBP1-DOCK_HTVS_1-001Lapatinib-5.78221-5.87101-50.1065
131_CTNND2_NRBP1-DOCK_HTVS_1-001Lapatinib-5.762490000000001-5.8512900000000005-49.9245
131_CTNND2_NRBP1-DOCK_HTVS_1-001Neratinib-5.749680000000001-6.65198-42.7589
131_CTNND2_NRBP1-DOCK_HTVS_1-001Neratinib-5.749680000000001-6.65198-42.7589
131_CTNND2_NRBP1-DOCK_HTVS_1-001Neratinib-5.71155-5.89745-43.7219
131_CTNND2_NRBP1-DOCK_HTVS_1-001Pexidartinib-5.69172-5.908519999999999-32.6485
131_CTNND2_NRBP1-DOCK_HTVS_1-001Pexidartinib-5.69172-5.908519999999999-32.6485
131_CTNND2_NRBP1-DOCK_HTVS_1-001Tofacitinib-5.6155-5.627000000000001-31.4039
131_CTNND2_NRBP1-DOCK_HTVS_1-001Tofacitinib-5.6155-5.627000000000001-31.4039
131_CTNND2_NRBP1-DOCK_HTVS_1-001Futibatinib-5.56844-5.56844-36.2122
131_CTNND2_NRBP1-DOCK_HTVS_1-001Afatinib-5.50199-5.68429-45.0568

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Kinase-Substrate Information of CTNND2_NRBP1


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain


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

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Related Drugs to CTNND2_NRBP1


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 CTNND2-NRBP1 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 CTNND2_NRBP1


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