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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
	Related Diseases

Fusion gene:ROCK1-GUCA2B (FusionGDB2 ID:75308)

Fusion Gene Summary for ROCK1-GUCA2B

Fusion gene summary

Fusion gene information	Fusion gene name: ROCK1-GUCA2B
	Fusion gene ID: 75308
		Hgene	Tgene
	Gene symbol	ROCK1	GUCA2B
	Gene ID	6093	2981
	Gene name	Rho associated coiled-coil containing protein kinase 1	guanylate cyclase activator 2B
	Synonyms	P160ROCK\|ROCK-I	GCAP-II\|UGN
	Cytomap	18q11.1	1p34.2
	Type of gene	protein-coding	protein-coding
	Description	rho-associated protein kinase 1p160 ROCK-1renal carcinoma antigen NY-REN-35	guanylate cyclase activator 2Bprepro-uroguanylinuroguanylin
	Modification date	20200322	20200313
	UniProtAcc	.	.
	Ensembl transtripts involved in fusion gene	ENST00000399799,	ENST00000372581,
Fusion gene scores	* DoF score	24 X 16 X 12=4608	3 X 2 X 3=18
	# samples	31	3
	** MAII score	log2(31/4608*10)=-3.89380059616807 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(3/18*10)=0.736965594166206 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Context	PubMed: ROCK1 [Title/Abstract] AND GUCA2B [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	ROCK1(18603581)-GUCA2B(42620351), # 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)

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	ROCK1	GO:0006468	protein phosphorylation	23093407
Hgene	ROCK1	GO:0007159	leukocyte cell-cell adhesion	12082081
Hgene	ROCK1	GO:0018105	peptidyl-serine phosphorylation	18573880
Hgene	ROCK1	GO:0022614	membrane to membrane docking	12082081
Hgene	ROCK1	GO:0030334	regulation of cell migration	23093407
Hgene	ROCK1	GO:0032091	negative regulation of protein binding	18573880
Hgene	ROCK1	GO:0032956	regulation of actin cytoskeleton organization	25911094
Hgene	ROCK1	GO:0050900	leukocyte migration	12082081
Hgene	ROCK1	GO:0050901	leukocyte tethering or rolling	12082081
Hgene	ROCK1	GO:0070507	regulation of microtubule cytoskeleton organization	23093407

Fusion gene breakpoints across ROCK1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across GUCA2B (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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.

Source	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	BLCA	TCGA-BT-A3PK-01A	ROCK1	chr18	18603581	-	GUCA2B	chr1	42620351	+

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Fusion Gene ORF analysis for ROCK1-GUCA2B

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.

ORF	Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
In-frame	ENST00000399799	ENST00000372581	ROCK1	chr18	18603581	-	GUCA2B	chr1	42620351	+

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

Henst

Tenst

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

Seq length
(transcript)

BP loci
(transcript)

Predicted start
(transcript)

Predicted stop
(transcript)

Seq length
(amino acids)

ENST00000399799

ROCK1

chr18

18603581

ENST00000372581

GUCA2B

chr1

42620351

2690

2213

899

2461

520

DeepORF 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.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	No-coding score	Coding score
ENST00000399799	ENST00000372581	ROCK1	chr18	18603581	-	GUCA2B	chr1	42620351	+	0.001690166	0.99830985

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Fusion Genomic Features for ROCK1-GUCA2B

FusionAI 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.

Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	1-p	p (fusion gene breakpoint)
ROCK1	chr18	18603580	-	GUCA2B	chr1	42620350	+	1.19E-07	0.9999999
ROCK1	chr18	18603580	-	GUCA2B	chr1	42620350	+	1.19E-07	0.9999999

Distribution 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.

Distribution 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 ROCK1-GUCA2B

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr18:18603581/chr1:42620351)
- 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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
.	.
FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.	FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.

Retention 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.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

341_409

424

1355.0

Domain

AGC-kinase C-terminal

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

76_338

424

1355.0

Domain

Protein kinase

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

82_90

424

1355.0

Nucleotide binding

ATP

- In-frame and not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

1011_1102

424

1355.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

422_692

424

1355.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

636_980

424

1355.0

Compositional bias

Note=Glu-rich

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

1118_1317

424

1355.0

Domain

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

479_556

424

1355.0

Domain

REM-1

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

949_1015

424

1355.0

Domain

RhoBD

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

1115_1354

424

1355.0

Region

Note=Auto-inhibitory

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

707_946

424

1355.0

Region

SHROOM3 binding

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

998_1010

424

1355.0

Region

Note=RHOA binding

Hgene

ROCK1

chr18:18603581

chr1:42620351

ENST00000399799

1228_1281

424

1355.0

Zinc finger

Phorbol-ester/DAG-type

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Fusion Gene Sequence for ROCK1-GUCA2B

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.

>75308_75308_1_ROCK1-GUCA2B_ROCK1_chr18_18603581_ENST00000399799_GUCA2B_chr1_42620351_ENST00000372581_length(transcript)=2690nt_BP=2213nt
GCTGGTTCCCCTTCCGAGCGTCCGCGCCCCGCATGCGCAGTCTGCCCCGGCGGTCTCCGTTTGTTTGAACAGGAAGGCGGACATATTAGT
CCCTCTCAGCCCCCCTCGCCCCACCCCCCAGGCATTCGCCGCCGCGACTCGCCCTTTCCCCGGCTGGGACCGCAGCCCCTCCCAGAAGCT
CCCCCATCAGCAGCCGCCGGGACCCAACTATCGTCTTCCTCTTCGCCCGCTCTCCAGCCTTTCCTCTGCTAAGTCTCCATCGGGCATCGA
CCTCGCCCTGCCCCACCGGACACCGTAGCAGCAGCCCCAGCAGCGACGGGACAAAATGGGAGAGTGAGGCTGTCCTGCGTGGACCAGCTC
GTGGCCGAGACTGATCGGTGCGTCGGGCCGGGCCGAGTAGAGCCGGGGACGCGGGGCTAGACCGTCTACAGCGCCTCTGAGCGGAGCGGG
CCCGGCCCGTGGCCCGAGCGGCGGCCGCAGCTGGCACAGCTCCTCACCCGCCCTTTGCTTTCGCCTTTCCTCTTCTCCCTCCCTTGTTGC
CCGGAGGGAGTCTCCACCCTGCTTCTCTTTCTCTACCCGCTCCTGCCCATCTCGGGACGGGGACCCCTCCATGGCGACGGCGGCCGGGGC
CCGCTAGACTGAAGCACCTCGCCGGAGCGACGAGGCTGGTGGCGACGGCGCTGTCGGCTGTCGTGAGGGGCTGCCGGGTGGGATGCGACT
TTGGGCGTCCGAGCGGCTGTGGGTCGCTGTTGCCCCCGGCCCGGGGTCTGGAGAGCGGAGGTCCCCTCAGTGAGGGGAAGACGGGGGAAC
CGGGCGCACCTGGTGACCCTGAGGTTCCGGCTCCTCCGCCCCGCGGCTGCGAACCCACCGCGGAGGAAGTTGGTTGAAATTGCTTTCCGC
TGCTGGTGCTGGTAAGAGGGCATTGTCACAGCAGCAGCAACATGTCGACTGGGGACAGTTTTGAGACTCGATTTGAAAAAATGGACAACC
TGCTGCGGGATCCCAAATCGGAAGTGAATTCGGATTGTTTGCTGGATGGATTGGATGCTTTGGTATATGATTTGGATTTTCCTGCCTTAA
GAAAAAACAAAAATATTGACAACTTTTTAAGCAGATATAAAGACACAATAAATAAAATCAGAGATTTACGAATGAAAGCTGAAGATTATG
AAGTAGTGAAGGTGATTGGTAGAGGTGCATTTGGAGAAGTTCAATTGGTAAGGCATAAATCCACCAGGAAGGTATATGCTATGAAGCTTC
TCAGCAAATTTGAAATGATAAAGAGATCTGATTCTGCTTTTTTCTGGGAAGAAAGGGACATCATGGCTTTTGCCAACAGTCCTTGGGTTG
TTCAGCTTTTTTATGCATTCCAAGATGATCGTTATCTCTACATGGTGATGGAATACATGCCTGGTGGAGATCTTGTAAACTTAATGAGCA
ACTATGATGTGCCTGAAAAATGGGCACGATTCTATACTGCAGAAGTAGTTCTTGCATTGGATGCAATCCATTCCATGGGTTTTATTCACA
GAGATGTGAAGCCTGATAACATGCTGCTGGATAAATCTGGACATTTGAAGTTAGCAGATTTTGGTACTTGTATGAAGATGAATAAGGAAG
GCATGGTACGATGTGATACAGCGGTTGGAACACCTGATTATATTTCCCCTGAAGTATTAAAATCCCAAGGTGGTGATGGTTATTATGGAA
GAGAATGTGACTGGTGGTCGGTTGGGGTATTTTTATACGAAATGCTTGTAGGTGATACACCTTTTTATGCAGATTCTTTGGTTGGAACTT
ACAGTAAAATTATGAACCATAAAAATTCACTTACCTTTCCTGATGATAATGACATATCAAAAGAAGCAAAAAACCTTATTTGTGCCTTCC
TTACTGACAGGGAAGTGAGGTTAGGGCGAAATGGTGTAGAAGAAATCAAACGACATCTCTTCTTCAAAAATGACCAGTGGGCTTGGGAAA
CGCTCCGAGACACTGTAGCACCAGTTGTACCCGATTTAAGTAGTGACATTGATACTAGTAATTTTGATGACTTGGAAGAAGATAAAGGAG
AGGAAGAAACATTCCCTATTCCTAAAGCTTTCGTTGGCAATCAACTACCTTTTGTAGGATTTACATATTATAGCAATCGTAGATACTTAT
CTTCAGCAAATCCTAATGATAACAGAACTAGCTCCAATGCAGATAAAAGCTTGTACCAAGGCTTCCGGGTCCAGCTGGAATCCATGAAGA
AGCTGAGTGACCTGGAGGCACAGTGGGCACCCAGCCCCCGCCTGCAGGCCCAGAGCCTCCTGCCCGCCGTGTGCCACCACCCTGCTCTGC
CTCAGGACCTTCAGCCTGTCTGCGCCTCGCAGGAGGCTTCCAGCATCTTCAAGACCCTGAGGACCATCGCTAACGACGACTGTGAGCTGT
GTGTGAACGTTGCGTGTACCGGCTGCCTCTGAGATAGCCCTGGGTACCCTGAGCCCACCAGGGACACCTCGCCCTTCAGCCCACCACCCT
GGCAGGCTTCCATCCCCGTCCATGCTCAAGATGGGTCCCTGGCCACCATGGTCATCACCACCCTTCCAGGGCCTGAGCAGCTGGATCTGG

>75308_75308_1_ROCK1-GUCA2B_ROCK1_chr18_18603581_ENST00000399799_GUCA2B_chr1_42620351_ENST00000372581_length(amino acids)=520AA_BP=438
MLVLVRGHCHSSSNMSTGDSFETRFEKMDNLLRDPKSEVNSDCLLDGLDALVYDLDFPALRKNKNIDNFLSRYKDTINKIRDLRMKAEDY
EVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEYMPGGDLVNLMS
NYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMNKEGMVRCDTAVGTPDYISPEVLKSQGGDGYYG
RECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMNHKNSLTFPDDNDISKEAKNLICAFLTDREVRLGRNGVEEIKRHLFFKNDQWAWE
TLRDTVAPVVPDLSSDIDTSNFDDLEEDKGEEETFPIPKAFVGNQLPFVGFTYYSNRRYLSSANPNDNRTSSNADKSLYQGFRVQLESMK

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

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Fusion Gene PPI Analysis for ROCK1-GUCA2B

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- Retained PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner	Gene	Hbp	Tbp	ENST	Strand	BPexon	TotalExon	Protein feature loci	*BPloci	TotalLen	Interaction lost with
Hgene	ROCK1	chr18:18603581	chr1:42620351	ENST00000399799	-	11	33	368_727	424.0	1355.0	FHOD1

- Retained PPIs, but lost function due to frame-shift fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs for ROCK1-GUCA2B

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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Related Diseases for ROCK1-GUCA2B

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source