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Center for Computational Systems Medicine level2
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:ARGLU1-CXCR4

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ARGLU1-CXCR4
FusionPDB ID: 5914
FusionGDB2.0 ID: 5914
HgeneTgene
Gene symbol

ARGLU1

CXCR4

Gene ID

55082

7852

Gene namearginine and glutamate rich 1C-X-C motif chemokine receptor 4
Synonyms-CD184|D2S201E|FB22|HM89|HSY3RR|LAP-3|LAP3|LCR1|LESTR|NPY3R|NPYR|NPYRL|NPYY3R|WHIM|WHIMS
Cytomap

13q33.3

2q22.1

Type of geneprotein-codingprotein-coding
Descriptionarginine and glutamate-rich protein 1C-X-C chemokine receptor type 4CD184 antigenLPS-associated protein 3SDF-1 receptorchemokine (C-X-C motif) receptor 4chemokine receptorfusinleukocyte-derived seven transmembrane domain receptorlipopolysaccharide-associated protein 3neuropeptide Y
Modification date2020031320200313
UniProtAcc

Q9NWB6

P61073

Ensembl transtripts involved in fusion geneENST idsENST00000400198, ENST00000375926, 
ENST00000472226, 
ENST00000466288, 
ENST00000409817, ENST00000241393, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 2=726 X 3 X 4=72
# samples 66
** MAII scorelog2(6/72*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/72*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: ARGLU1 [Title/Abstract] AND CXCR4 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ARGLU1(107219921)-CXCR4(136873482), # samples:3
Anticipated loss of major functional domain due to fusion event.ARGLU1-CXCR4 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.
ARGLU1-CXCR4 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.
ARGLU1-CXCR4 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.
ARGLU1-CXCR4 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.
ARGLU1-CXCR4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
ARGLU1-CXCR4 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
ARGLU1-CXCR4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted 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
TgeneCXCR4

GO:0007186

G protein-coupled receptor signaling pathway

10644702

TgeneCXCR4

GO:0030155

regulation of cell adhesion

19703720

TgeneCXCR4

GO:0038160

CXCL12-activated CXCR4 signaling pathway

28978524

TgeneCXCR4

GO:0071345

cellular response to cytokine stimulus

21540189


check buttonFusion gene breakpoints across ARGLU1 (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 CXCR4 (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 Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4PRADTCGA-KK-A59X-01AARGLU1chr13

107219921

-CXCR4chr2

136873482

-
ChimerDB4PRADTCGA-KK-A59XARGLU1chr13

107219921

-CXCR4chr2

136873482

-


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Fusion ORF Analysis


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)
ENST00000400198ARGLU1chr13107219921-ENST00000241393CXCR4chr2136873482-21545926221635337

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
ENST00000400198ENST00000241393ARGLU1chr13107219921-CXCR4chr2136873482-0.016450560.9835495

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>5914_5914_1_ARGLU1-CXCR4_ARGLU1_chr13_107219921_ENST00000400198_CXCR4_chr2_136873482_ENST00000241393_length(amino acids)=337AA_BP=
MGSGDYDSMKEPCFREENANFNKIFLPTIYSIIFLTGIVGNGLVILVMGYQKKLRSMTDKYRLHLSVADLLFVITLPFWAVDAVANWYFG
NFLCKAVHVIYTVNLYSSVLILAFISLDRYLAIVHATNSQRPRKLLAEKVVYVGVWIPALLLTIPDFIFANVSEADDRYICDRFYPNDLW
VVVFQFQHIMVGLILPGIVILSCYCIIISKLSHSKGHQKRKALKTTVILILAFFACWLPYYIGISIDSFILLEIIKQGCEFENTVHKWIS

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

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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/chr13:107219921/chr2:136873482)
- 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
ARGLU1

Q9NWB6

CXCR4

P61073

FUNCTION: Required for the estrogen-dependent expression of ESR1 target genes. Can act in cooperation with MED1. {ECO:0000269|PubMed:21454576}.FUNCTION: Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:28978524, PubMed:18799424, PubMed:24912431). Involved in the AKT signaling cascade (PubMed:24912431). Plays a role in regulation of cell migration, e.g. during wound healing (PubMed:28978524). Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels (PubMed:20228059). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival (By similarity). {ECO:0000250|UniProtKB:P70658, ECO:0000269|PubMed:10074102, ECO:0000269|PubMed:10452968, ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:10825158, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:17197449, ECO:0000269|PubMed:18799424, ECO:0000269|PubMed:20048153, ECO:0000269|PubMed:20228059, ECO:0000269|PubMed:20505072, ECO:0000269|PubMed:24912431, ECO:0000269|PubMed:28978524, ECO:0000269|PubMed:8752280, ECO:0000269|PubMed:8752281}.; FUNCTION: (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) for human immunodeficiency virus-1/HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus (PubMed:8849450, PubMed:8929542, PubMed:9427609, PubMed:10074122, PubMed:10756055). {ECO:0000269|PubMed:10074122, ECO:0000269|PubMed:10756055, ECO:0000269|PubMed:8849450, ECO:0000269|PubMed:8929542, ECO:0000269|PubMed:9427609}.

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.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneARGLU1chr13:107219921chr2:136873482ENST00000400198-143_74115.66666666666667274.0Compositional biasNote=Arg-rich
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302133_1355.0353.0MotifNote=Important for signaling
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701133_1350357.0MotifNote=Important for signaling
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302113_1175.0353.0RegionNote=Chemokine binding
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302135_1475.0353.0RegionNote=Involved in dimerization%3B when bound to chemokine
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302186_1905.0353.0RegionNote=Chemokine binding%2C important for signaling and HIV-1 coreceptor activity
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302191_2105.0353.0RegionNote=Involved in dimerization
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302266_2685.0353.0RegionNote=Involved in dimerization
TgeneCXCR4chr13:107219921chr2:136873482ENST000002413930294_975.0353.0RegionChemokine binding
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701113_1170357.0RegionNote=Chemokine binding
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701135_1470357.0RegionNote=Involved in dimerization%3B when bound to chemokine
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701186_1900357.0RegionNote=Chemokine binding%2C important for signaling and HIV-1 coreceptor activity
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701191_2100357.0RegionNote=Involved in dimerization
TgeneCXCR4chr13:107219921chr2:136873482ENST00000409817011_210357.0RegionImportant for chemokine binding%2C signaling and HIV-1 coreceptor activity
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701266_2680357.0RegionNote=Involved in dimerization
TgeneCXCR4chr13:107219921chr2:136873482ENST000004098170194_970357.0RegionChemokine binding
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302100_1105.0353.0Topological domainExtracellular
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302131_1545.0353.0Topological domainCytoplasmic
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302175_1955.0353.0Topological domainExtracellular
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302217_2415.0353.0Topological domainCytoplasmic
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302262_2825.0353.0Topological domainExtracellular
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302303_3525.0353.0Topological domainCytoplasmic
TgeneCXCR4chr13:107219921chr2:136873482ENST000002413930264_775.0353.0Topological domainCytoplasmic
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701100_1100357.0Topological domainExtracellular
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701131_1540357.0Topological domainCytoplasmic
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701175_1950357.0Topological domainExtracellular
TgeneCXCR4chr13:107219921chr2:136873482ENST00000409817011_380357.0Topological domainExtracellular
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701217_2410357.0Topological domainCytoplasmic
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701262_2820357.0Topological domainExtracellular
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701303_3520357.0Topological domainCytoplasmic
TgeneCXCR4chr13:107219921chr2:136873482ENST000004098170164_770357.0Topological domainCytoplasmic
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302111_1305.0353.0TransmembraneHelical%3B Name%3D3
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302155_1745.0353.0TransmembraneHelical%3B Name%3D4
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302196_2165.0353.0TransmembraneHelical%3B Name%3D5
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302242_2615.0353.0TransmembraneHelical%3B Name%3D6
TgeneCXCR4chr13:107219921chr2:136873482ENST0000024139302283_3025.0353.0TransmembraneHelical%3B Name%3D7
TgeneCXCR4chr13:107219921chr2:136873482ENST000002413930239_635.0353.0TransmembraneHelical%3B Name%3D1
TgeneCXCR4chr13:107219921chr2:136873482ENST000002413930278_995.0353.0TransmembraneHelical%3B Name%3D2
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701111_1300357.0TransmembraneHelical%3B Name%3D3
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701155_1740357.0TransmembraneHelical%3B Name%3D4
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701196_2160357.0TransmembraneHelical%3B Name%3D5
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701242_2610357.0TransmembraneHelical%3B Name%3D6
TgeneCXCR4chr13:107219921chr2:136873482ENST0000040981701283_3020357.0TransmembraneHelical%3B Name%3D7
TgeneCXCR4chr13:107219921chr2:136873482ENST000004098170139_630357.0TransmembraneHelical%3B Name%3D1
TgeneCXCR4chr13:107219921chr2:136873482ENST000004098170178_990357.0TransmembraneHelical%3B Name%3D2

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneARGLU1chr13:107219921chr2:136873482ENST00000400198-1497_251115.66666666666667274.0Compositional biasNote=Glu-rich
TgeneCXCR4chr13:107219921chr2:136873482ENST00000241393021_215.0353.0RegionImportant for chemokine binding%2C signaling and HIV-1 coreceptor activity
TgeneCXCR4chr13:107219921chr2:136873482ENST00000241393021_385.0353.0Topological domainExtracellular


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Fusion Protein Structures

check button PDB and CIF files of the predicted 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.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file >>>635_ARGLU1_107219921_CXCR4_136873482_ranked_0.pdbARGLU1107219921107219921ENST00000241393CXCR4chr2136873482-
MGSGDYDSMKEPCFREENANFNKIFLPTIYSIIFLTGIVGNGLVILVMGYQKKLRSMTDKYRLHLSVADLLFVITLPFWAVDAVANWYFG
NFLCKAVHVIYTVNLYSSVLILAFISLDRYLAIVHATNSQRPRKLLAEKVVYVGVWIPALLLTIPDFIFANVSEADDRYICDRFYPNDLW
VVVFQFQHIMVGLILPGIVILSCYCIIISKLSHSKGHQKRKALKTTVILILAFFACWLPYYIGISIDSFILLEIIKQGCEFENTVHKWIS
337


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
ARGLU1_pLDDT.png
all structure
all structure
CXCR4_pLDDT.png
all structure
all structure

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.
all structure


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Ramachandran Plot of 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.
Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
ARGLU1
CXCR4


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to ARGLU1-CXCR4


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 ARGLU1-CXCR4


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