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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:GPRC5A-NRG1 (FusionGDB2 ID:34494)

Fusion Gene Summary for GPRC5A-NRG1

check button Fusion gene summary
Fusion gene informationFusion gene name: GPRC5A-NRG1
Fusion gene ID: 34494
HgeneTgene
Gene symbol

GPRC5A

NRG1

Gene ID

9052

3084

Gene nameG protein-coupled receptor class C group 5 member Aneuregulin 1
SynonymsGPCR5A|PEIG-1|RAI3|RAIG1|TIG1ARIA|GGF|GGF2|HGL|HRG|HRG1|HRGA|MST131|MSTP131|NDF|NRG1-IT2|SMDF
Cytomap

12p13.1

8p12

Type of geneprotein-codingprotein-coding
Descriptionretinoic acid-induced protein 3G-protein coupled receptor family C group 5 member ATPA induced gene 1orphan G-protein-coupling receptor PEIG-1phorbol ester induced gene 1phorbol ester induced protein-1retinoic acid induced 3retinoic acid responsivepro-neuregulin-1, membrane-bound isoformacetylcholine receptor-inducing activityglial growth factor 2heregulin, alpha (45kD, ERBB2 p185-activator)neu differentiation factorpro-NRG1sensory and motor neuron derived factor
Modification date2020031320200320
UniProtAcc

Q8NFJ5

Q02297

Ensembl transtripts involved in fusion geneENST00000542056, ENST00000014914, 
ENST00000287842, ENST00000287845, 
ENST00000338921, ENST00000341377, 
ENST00000356819, ENST00000405005, 
ENST00000519301, ENST00000520407, 
ENST00000521670, ENST00000523079, 
ENST00000520502, ENST00000523681, 
ENST00000539990, 
Fusion gene scores* DoF score9 X 6 X 4=21625 X 17 X 14=5950
# samples 1127
** MAII scorelog2(11/216*10)=-0.973527788638809
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(27/5950*10)=-4.46185835603184
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: GPRC5A [Title/Abstract] AND NRG1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointGPRC5A(13044598)-NRG1(32453346), # samples:3
Anticipated loss of major functional domain due to fusion event.
* 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
TgeneNRG1

GO:0003222

ventricular trabecula myocardium morphogenesis

17336907

TgeneNRG1

GO:0031334

positive regulation of protein complex assembly

10559227

TgeneNRG1

GO:0038127

ERBB signaling pathway

11389077

TgeneNRG1

GO:0038129

ERBB3 signaling pathway

27353365

TgeneNRG1

GO:0045892

negative regulation of transcription, DNA-templated

15073182

TgeneNRG1

GO:0051048

negative regulation of secretion

10559227

TgeneNRG1

GO:0060379

cardiac muscle cell myoblast differentiation

17336907

TgeneNRG1

GO:0060956

endocardial cell differentiation

17336907


check buttonFusion gene breakpoints across GPRC5A (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 NRG1 (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-B7-A5TN-01AGPRC5Achr12

13044598

-NRG1chr8

32453346

+
ChimerDB4STADTCGA-B7-A5TN-01AGPRC5Achr12

13044598

+NRG1chr8

32453346

+
ChimerDB4STADTCGA-B7-A5TNGPRC5Achr12

13044598

+NRG1chr8

32453345

+


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Fusion Gene ORF analysis for GPRC5A-NRG1

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
3UTR-3CDSENST00000542056ENST00000287842GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000287842GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-3CDSENST00000542056ENST00000287845GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000287845GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-3CDSENST00000542056ENST00000338921GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000338921GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-3CDSENST00000542056ENST00000341377GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000341377GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-3CDSENST00000542056ENST00000356819GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000356819GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-3CDSENST00000542056ENST00000405005GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000405005GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-3CDSENST00000542056ENST00000519301GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000519301GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-3CDSENST00000542056ENST00000520407GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000520407GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-3CDSENST00000542056ENST00000521670GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000521670GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-3CDSENST00000542056ENST00000523079GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-3CDSENST00000542056ENST00000523079GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-intronENST00000542056ENST00000520502GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-intronENST00000542056ENST00000520502GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-intronENST00000542056ENST00000523681GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-intronENST00000542056ENST00000523681GPRC5Achr12

13044598

+NRG1chr8

32453345

+
3UTR-intronENST00000542056ENST00000539990GPRC5Achr12

13044598

+NRG1chr8

32453346

+
3UTR-intronENST00000542056ENST00000539990GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000287842GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000287842GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000287845GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000287845GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000338921GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000338921GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000341377GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000341377GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000356819GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000356819GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000405005GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000405005GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000519301GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000519301GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000520407GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000520407GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000521670GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000521670GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-3CDSENST00000014914ENST00000523079GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-3CDSENST00000014914ENST00000523079GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-intronENST00000014914ENST00000520502GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-intronENST00000014914ENST00000520502GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-intronENST00000014914ENST00000523681GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-intronENST00000014914ENST00000523681GPRC5Achr12

13044598

+NRG1chr8

32453345

+
5UTR-intronENST00000014914ENST00000539990GPRC5Achr12

13044598

+NRG1chr8

32453346

+
5UTR-intronENST00000014914ENST00000539990GPRC5Achr12

13044598

+NRG1chr8

32453345

+

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 GPRC5A-NRG1


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)
GPRC5Achr1213044598+NRG1chr832453345+0.0025364260.9974636
GPRC5Achr1213044598+NRG1chr832453345+0.0025364260.9974636
GPRC5Achr1213044598+NRG1chr832453345+0.0025364260.9974636
GPRC5Achr1213044598+NRG1chr832453345+0.0025364260.9974636

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.
genomic feature of top 1%

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Fusion Protein Features for GPRC5A-NRG1


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/:13044598/:32453346)
- 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
GPRC5A

Q8NFJ5

NRG1

Q02297

FUNCTION: Orphan receptor. Could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways. Functions as a negative modulator of EGFR signaling (By similarity). May act as a lung tumor suppressor (PubMed:18000218). {ECO:0000250|UniProtKB:Q8BHL4, ECO:0000269|PubMed:18000218}.FUNCTION: Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4 (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons (By similarity). {ECO:0000250|UniProtKB:P43322, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:1348215, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:7902537}.

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 GPRC5A-NRG1


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 GPRC5A-NRG1


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 GPRC5A-NRG1


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 GPRC5A-NRG1


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