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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:GRK5-UNC5C (FusionGDB2 ID:34890)

Fusion Gene Summary for GRK5-UNC5C

check button Fusion gene summary
Fusion gene informationFusion gene name: GRK5-UNC5C
Fusion gene ID: 34890
HgeneTgene
Gene symbol

GRK5

UNC5C

Gene ID

2869

8633

Gene nameG protein-coupled receptor kinase 5unc-5 netrin receptor C
SynonymsFP2025|GPRK5UNC5H3
Cytomap

10q26.11

4q22.3

Type of geneprotein-codingprotein-coding
DescriptionG protein-coupled receptor kinase 5g protein-coupled receptor kinase GRK5netrin receptor UNC5Cprotein unc-5 homolog 3protein unc-5 homolog Cunc-5 homolog 3unc-5 homolog Cunc5 (C.elegans homolog) c
Modification date2020031320200313
UniProtAcc

P34947

UNC5CL

Ensembl transtripts involved in fusion geneENST00000369108, ENST00000392870, 
ENST00000473264, 
ENST00000504962, 
ENST00000506749, ENST00000453304, 
Fusion gene scores* DoF score8 X 8 X 4=2564 X 4 X 3=48
# samples 94
** MAII scorelog2(9/256*10)=-1.50814690367033
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: GRK5 [Title/Abstract] AND UNC5C [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointGRK5(121156284)-UNC5C(96127947), # samples:1
Anticipated loss of major functional domain due to fusion event.GRK5-UNC5C seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
GRK5-UNC5C seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
GRK5-UNC5C seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
GRK5-UNC5C seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgeneGRK5

GO:0007217

tachykinin receptor signaling pathway

17986524

HgeneGRK5

GO:0043066

negative regulation of apoptotic process

20124405

HgeneGRK5

GO:0046777

protein autophosphorylation

14976207

TgeneUNC5C

GO:1990791

dorsal root ganglion development

28483977


check buttonFusion gene breakpoints across GRK5 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across UNC5C (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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
ChimerDB4STADTCGA-BR-8365-01AGRK5chr10

121156284

+UNC5Cchr4

96127947

-


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Fusion Gene ORF analysis for GRK5-UNC5C

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5CDS-intronENST00000369108ENST00000504962GRK5chr10

121156284

+UNC5Cchr4

96127947

-
5CDS-intronENST00000369108ENST00000506749GRK5chr10

121156284

+UNC5Cchr4

96127947

-
5CDS-intronENST00000392870ENST00000504962GRK5chr10

121156284

+UNC5Cchr4

96127947

-
5CDS-intronENST00000392870ENST00000506749GRK5chr10

121156284

+UNC5Cchr4

96127947

-
Frame-shiftENST00000369108ENST00000453304GRK5chr10

121156284

+UNC5Cchr4

96127947

-
Frame-shiftENST00000392870ENST00000453304GRK5chr10

121156284

+UNC5Cchr4

96127947

-
intron-3CDSENST00000473264ENST00000453304GRK5chr10

121156284

+UNC5Cchr4

96127947

-
intron-intronENST00000473264ENST00000504962GRK5chr10

121156284

+UNC5Cchr4

96127947

-
intron-intronENST00000473264ENST00000506749GRK5chr10

121156284

+UNC5Cchr4

96127947

-

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)

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

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Fusion Genomic Features for GRK5-UNC5C


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for GRK5-UNC5C


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/:121156284/:96127947)
- 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
GRK5

P34947

UNC5C

UNC5CL

FUNCTION: Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro). {ECO:0000269|PubMed:19661922, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20038610, ECO:0000269|PubMed:20124405, ECO:0000269|PubMed:21728385}.518

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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for GRK5-UNC5C


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for GRK5-UNC5C


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 (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for GRK5-UNC5C


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for GRK5-UNC5C


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