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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:VPS53_ABR

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: VPS53_ABR
KinaseFusionDB ID: KFG7073
FusionGDB2.0 ID: KFG7073
HgeneTgene
Gene symbol

VPS53

ABR

Gene ID

55275

29

Gene nameVPS53 subunit of GARP complexABR activator of RhoGEF and GTPase
SynonymsHCCS1|PCH2E|hVps53L|pp13624MDB
Cytomap

17p13.3

17p13.3

Type of geneprotein-codingprotein-coding
Descriptionvacuolar protein sorting-associated protein 53 homologVPS53, GARP complex subunithepatocellular carcinoma suppressor 1active breakpoint cluster region-related proteinABR, RhoGEF and GTPase activating proteinactive BCR-related
Modification date2024041120240302
UniProtAcc

Q5VIR6

Q9P1F3

Ensembl transtripts involved in fusion geneENST idsENST00000291074, ENST00000401468, 
ENST00000437048, ENST00000571805, 
ENST00000446250, ENST00000574029, 
ENST00000576149, 
ENST00000291107, 
ENST00000536794, ENST00000543210, 
ENST00000572441, ENST00000573895, 
ENST00000574437, ENST00000302538, 
ENST00000544583, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: VPS53 [Title/Abstract] AND ABR [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VPS53(600658)-ABR(1003975), # 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
TgeneABR

GO:0090630

activation of GTPase activity

7479768


check buttonKinase Fusion gene breakpoints across VPS53 (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 ABR (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-CV-A45X-01AVPS53chr17

600658

ABRchr17

1003975



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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)
ENST00000437048ENST00000302538VPS53chr17600658ABRchr1710039755328872

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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

>ENST00000437048_ENST00000302538_VPS53_chr17_600658_ABR_chr17_1003975_length(amino acids)=872
MMEEEELEFVEELEAVLQLTPEVQLAIEQVFPSQDPLDRADFNAVEYINTLFPTEQSLANIDEVVNKIRLKIRRLDDNIRTVVRGQTNVG
QDGRQVEAGKGLEMRKLVLSGFLASEEIYINQLEALLLPMKPLKATATTSQPVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWDSQ
VTMGHLFQKLASQLGVYKAFVDNYKVALETAEKCSQSNNQFQKISEELKVKGPKDSKDSHTSVTMEALLYKPIDRVTRSTLVLHDLLKHT
PVDHPDYPLLQDALRISQNFLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCK
WYIPLADLVFPSPEESEASPQVHPFPDHELEDMKMKISALKSEIQKEKANKGQSRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGKSY
LFLLSSDYERSEWREAIQKLQKKDLQAFVLSSVELQVLTGSCFKLRTVHNIPVTSNKDDDESPGLYGFLHVIVHSAKGFKQSANLYCTLE
VDSFGYFVSKAKTRVFRDTAEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVNKDNNEIVDKIMGKGQIQLDPQTVETKNWHTDVIEMNG
IKVEFSMKFTSRDMSLKRTPSKKQTGVFGVKISVVTKRERSKVPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILL
MLSDMDINAIAGTLKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLA

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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/chr17:600658/chr17:1003975)
- 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
VPS53

Q5VIR6

ABR

Q9P1F3

FUNCTION: Acts as a component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD (PubMed:15878329, PubMed:18367545). Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane (PubMed:25799061). {ECO:0000269|PubMed:15878329, ECO:0000269|PubMed:18367545, ECO:0000269|PubMed:25799061}.

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
TgeneVPS53600658ABR1003975ENST00000437048022484_61336814DomainNote=C2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00041
TgeneVPS53600658ABR1003975ENST00000437048022484_61345823DomainNote=C2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00041
TgeneVPS53600658ABR1003975ENST0000043704808484_6130311DomainNote=C2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00041
TgeneVPS53600658ABR1003975ENST00000437048123484_61336814DomainNote=C2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00041
TgeneVPS53600658ABR1003975ENST00000437048123484_61382860DomainNote=C2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00041
TgeneVPS53600658ABR1003975ENST0000043704802291_28436814DomainNote=DH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00062
TgeneVPS53600658ABR1003975ENST0000043704802291_28445823DomainNote=DH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00062
TgeneVPS53600658ABR1003975ENST000004370480891_2840311DomainNote=DH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00062
TgeneVPS53600658ABR1003975ENST0000043704812391_28436814DomainNote=DH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00062
TgeneVPS53600658ABR1003975ENST0000043704812391_28482860DomainNote=DH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00062
TgeneVPS53600658ABR1003975ENST00000437048022301_45936814DomainNote=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00145
TgeneVPS53600658ABR1003975ENST00000437048022301_45945823DomainNote=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00145
TgeneVPS53600658ABR1003975ENST0000043704808301_4590311DomainNote=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00145
TgeneVPS53600658ABR1003975ENST00000437048123301_45936814DomainNote=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00145
TgeneVPS53600658ABR1003975ENST00000437048123301_45982860DomainNote=PH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00145
TgeneVPS53600658ABR1003975ENST00000437048022647_84536814DomainNote=Rho-GAP;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00172
TgeneVPS53600658ABR1003975ENST00000437048022647_84545823DomainNote=Rho-GAP;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00172
TgeneVPS53600658ABR1003975ENST0000043704808647_8450311DomainNote=Rho-GAP;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00172
TgeneVPS53600658ABR1003975ENST00000437048123647_84536814DomainNote=Rho-GAP;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00172
TgeneVPS53600658ABR1003975ENST00000437048123647_84582860DomainNote=Rho-GAP;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00172


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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 >>>553_VPS53_ABRENST00000437048ENST00000302538VPS53chr17600658ABRchr171003975
MMEEEELEFVEELEAVLQLTPEVQLAIEQVFPSQDPLDRADFNAVEYINTLFPTEQSLANIDEVVNKIRLKIRRLDDNIRTVVRGQTNVG
QDGRQVEAGKGLEMRKLVLSGFLASEEIYINQLEALLLPMKPLKATATTSQPVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWDSQ
VTMGHLFQKLASQLGVYKAFVDNYKVALETAEKCSQSNNQFQKISEELKVKGPKDSKDSHTSVTMEALLYKPIDRVTRSTLVLHDLLKHT
PVDHPDYPLLQDALRISQNFLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCK
WYIPLADLVFPSPEESEASPQVHPFPDHELEDMKMKISALKSEIQKEKANKGQSRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGKSY
LFLLSSDYERSEWREAIQKLQKKDLQAFVLSSVELQVLTGSCFKLRTVHNIPVTSNKDDDESPGLYGFLHVIVHSAKGFKQSANLYCTLE
VDSFGYFVSKAKTRVFRDTAEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVNKDNNEIVDKIMGKGQIQLDPQTVETKNWHTDVIEMNG
IKVEFSMKFTSRDMSLKRTPSKKQTGVFGVKISVVTKRERSKVPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILL
MLSDMDINAIAGTLKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLA
872
3D view using mol* of 553_VPS53_ABR
PDB file >>>TKFP_944_VPS53_ABRENST00000437048ENST00000302538VPS53chr17600658ABRchr171003975
MMEEEELEFVEELEAVLQLTPEVQLAIEQVFPSQDPLDRADFNAVEYINTLFPTEQSLANIDEVVNKIRLKIRRLDDNIRTVVRGQTNVG
QDGRQVEAGKGLEMRKLVLSGFLASEEIYINQLEALLLPMKPLKATATTSQPVLTIQQIETIFYKIQDIYEIHKEFYDNLCPKVQQWDSQ
VTMGHLFQKLASQLGVYKAFVDNYKVALETAEKCSQSNNQFQKISEELKVKGPKDSKDSHTSVTMEALLYKPIDRVTRSTLVLHDLLKHT
PVDHPDYPLLQDALRISQNFLSSINEDIDPRRTAVTTPKGETRQLVKDGFLVEVSESSRKLRHVFLFTDVLLCAKLKKTSAGKHQQYDCK
WYIPLADLVFPSPEESEASPQVHPFPDHELEDMKMKISALKSEIQKEKANKGQSRAIERLKKKMFENEFLLLLNSPTIPFRIHNRNGKSY
LFLLSSDYERSEWREAIQKLQKKDLQAFVLSSVELQVLTGSCFKLRTVHNIPVTSNKDDDESPGLYGFLHVIVHSAKGFKQSANLYCTLE
VDSFGYFVSKAKTRVFRDTAEPKWDEEFEIELEGSQSLRILCYEKCYDKTKVNKDNNEIVDKIMGKGQIQLDPQTVETKNWHTDVIEMNG
IKVEFSMKFTSRDMSLKRTPSKKQTGVFGVKISVVTKRERSKVPYIVRQCVEEVEKRGIEEVGIYRISGVATDIQALKAVFDANNKDILL
MLSDMDINAIAGTLKLYFRELPEPLLTDRLYPAFMEGIALSDPAAKENCMMHLLRSLPDPNLITFLFLLEHLKRVAEKEPINKMSLHNLA
872_VPS53_ABR


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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

VPS53_ABR does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/553_VPS53_ABR.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.
553_VPS53_ABR.png
all structure sitemap plddt3 553_VPS53_ABR.png
553_VPS53_ABR.png
all structure sitemap plddt4 553_VPS53_ABR.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.

553_VPS53_ABR_ramachandran.png
all structure VPS53-ABR

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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 VPS53-ABR

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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
553_VPS53_ABR-DOCK_HTVS_1-001Entrectinib-6.76748-6.83218-55.2465
553_VPS53_ABR-DOCK_HTVS_1-001Entrectinib-6.7203-6.785-53.6308
553_VPS53_ABR-DOCK_HTVS_1-001Entrectinib-6.7203-6.785-53.6308
553_VPS53_ABR-DOCK_HTVS_1-001Midostaurin-6.590260000000001-6.590260000000001-51.4502
553_VPS53_ABR-DOCK_HTVS_1-001Cobimetinib-6.13542-6.13822-46.9512
553_VPS53_ABR-DOCK_HTVS_1-001Nilotinib-6.11803-7.04283-51.1191
553_VPS53_ABR-DOCK_HTVS_1-001Nilotinib-6.11803-7.04283-51.1191
553_VPS53_ABR-DOCK_HTVS_1-001Neratinib-6.08006-6.26596-58.2443
553_VPS53_ABR-DOCK_HTVS_1-001Gilteritinib-6.0731-6.0995-53.5481
553_VPS53_ABR-DOCK_HTVS_1-001Gilteritinib-6.0731-6.0995-53.5481
553_VPS53_ABR-DOCK_HTVS_1-001Mobocertinib-6.03594-6.04364-55.3792
553_VPS53_ABR-DOCK_HTVS_1-001Midostaurin-6.0092099999999995-6.0092099999999995-43.0789
553_VPS53_ABR-DOCK_HTVS_1-001Fedratinib-5.82987-5.88127-54.3537
553_VPS53_ABR-DOCK_HTVS_1-001Fedratinib-5.82987-5.88127-54.3537
553_VPS53_ABR-DOCK_HTVS_1-001Nilotinib-5.78939-5.92899-52.1914
553_VPS53_ABR-DOCK_HTVS_1-001Nilotinib-5.78939-5.92899-52.1914
553_VPS53_ABR-DOCK_HTVS_1-001Cobimetinib-5.78644-5.78924-43.7041
553_VPS53_ABR-DOCK_HTVS_1-001Palbociclib-5.67296-6.07986-46.0855
553_VPS53_ABR-DOCK_HTVS_1-001Neratinib-5.57647-5.758769999999999-58.2061
553_VPS53_ABR-DOCK_HTVS_1-001Neratinib-5.57647-5.758769999999999-58.2061

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Kinase-Substrate Information of VPS53_ABR


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 VPS53_ABR


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 VPS53-ABR 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 VPS53_ABR


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