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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:TYK2-CIB3 (FusionGDB2 ID:95650)

Fusion Gene Summary for TYK2-CIB3

Fusion gene summary

Fusion gene information	Fusion gene name: TYK2-CIB3
	Fusion gene ID: 95650
		Hgene	Tgene
	Gene symbol	TYK2	CIB3
	Gene ID	7297	117286
	Gene name	tyrosine kinase 2	calcium and integrin binding family member 3
	Synonyms	IMD35\|JTK1	KIP3
	Cytomap	19p13.2	19p13.11
	Type of gene	protein-coding	protein-coding
	Description	non-receptor tyrosine-protein kinase TYK2	calcium and integrin-binding family member 3DNA-dependent protein kinase catalytic subunit-interacting protein 3
	Modification date	20200329	20200313
	UniProtAcc	.	Q96Q77
	Ensembl transtripts involved in fusion gene	ENST00000264818, ENST00000525621, ENST00000529370, ENST00000524462, ENST00000529422,	ENST00000541493, ENST00000269878, ENST00000379859,
Fusion gene scores	* DoF score	13 X 11 X 8=1144	6 X 5 X 5=150
	# samples	15	9
	** MAII score	log2(15/1144*10)=-2.93105264628251 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(9/150*10)=-0.736965594166206 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context	PubMed: TYK2 [Title/Abstract] AND CIB3 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	TYK2(10488890)-CIB3(16275724), # samples:2
Anticipated loss of major functional domain due to fusion event.	TYK2-CIB3 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. TYK2-CIB3 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. TYK2-CIB3 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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)

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

Fusion gene breakpoints across TYK2 (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 CIB3 (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	SARC	TCGA-DX-A3LY-01B	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-

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Fusion Gene ORF analysis for TYK2-CIB3

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
5CDS-5UTR	ENST00000264818	ENST00000541493	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
5CDS-5UTR	ENST00000525621	ENST00000541493	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
5CDS-5UTR	ENST00000529370	ENST00000541493	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
Frame-shift	ENST00000264818	ENST00000269878	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
Frame-shift	ENST00000264818	ENST00000379859	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
In-frame	ENST00000525621	ENST00000269878	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
In-frame	ENST00000525621	ENST00000379859	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
In-frame	ENST00000529370	ENST00000269878	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
In-frame	ENST00000529370	ENST00000379859	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
intron-3CDS	ENST00000524462	ENST00000269878	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
intron-3CDS	ENST00000524462	ENST00000379859	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
intron-3CDS	ENST00000529422	ENST00000269878	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
intron-3CDS	ENST00000529422	ENST00000379859	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
intron-5UTR	ENST00000524462	ENST00000541493	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-
intron-5UTR	ENST00000529422	ENST00000541493	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-

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)
ENST00000525621	TYK2	chr19	10488890	-	ENST00000269878	CIB3	chr19	16275724	-	990	675	482	892	136
ENST00000525621	TYK2	chr19	10488890	-	ENST00000379859	CIB3	chr19	16275724	-	943	675	482	892	136
ENST00000529370	TYK2	chr19	10488890	-	ENST00000269878	CIB3	chr19	16275724	-	839	524	331	741	136
ENST00000529370	TYK2	chr19	10488890	-	ENST00000379859	CIB3	chr19	16275724	-	792	524	331	741	136

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
ENST00000525621	ENST00000269878	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-	0.014877766	0.9851222
ENST00000525621	ENST00000379859	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-	0.012803899	0.9871961
ENST00000529370	ENST00000269878	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-	0.010022806	0.9899771
ENST00000529370	ENST00000379859	TYK2	chr19	10488890	-	CIB3	chr19	16275724	-	0.00954628	0.9904537

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Fusion Genomic Features for TYK2-CIB3

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)

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 TYK2-CIB3

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:10488890/chr19:16275724)
- 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
.	CIB3 Q96Q77
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

Tgene

CIB3

chr19:10488890

chr19:16275724

ENST00000269878

116_127

115

188.0

Calcium binding

Tgene

CIB3

chr19:10488890

chr19:16275724

ENST00000269878

157_168

115

188.0

Calcium binding

Tgene

CIB3

chr19:10488890

chr19:16275724

ENST00000269878

144_179

115

188.0

Domain

EF-hand 3

- 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

TYK2

chr19:10488890

chr19:16275724

ENST00000264818

26_431

1188.0

Domain

FERM

Hgene

TYK2

chr19:10488890

chr19:16275724

ENST00000264818

450_529

1188.0

Domain

Note=SH2%3B atypical

Hgene

TYK2

chr19:10488890

chr19:16275724

ENST00000264818

589_875

1188.0

Domain

Protein kinase 1

Hgene

TYK2

chr19:10488890

chr19:16275724

ENST00000264818

897_1176

1188.0

Domain

Protein kinase 2

Hgene

TYK2

chr19:10488890

chr19:16275724

ENST00000525621

26_431

1188.0

Domain

FERM

Hgene

TYK2

chr19:10488890

chr19:16275724

ENST00000525621

450_529

1188.0

Domain

Note=SH2%3B atypical

Hgene

TYK2

chr19:10488890

chr19:16275724

ENST00000525621

589_875

1188.0

Domain

Protein kinase 1

Hgene

TYK2

chr19:10488890

chr19:16275724

ENST00000525621

897_1176

1188.0

Domain

Protein kinase 2

Hgene

TYK2

chr19:10488890

chr19:16275724

ENST00000264818

903_911

1188.0

Nucleotide binding

ATP

Hgene

TYK2

chr19:10488890

chr19:16275724

ENST00000525621

903_911

1188.0

Nucleotide binding

ATP

Tgene

CIB3

chr19:10488890

chr19:16275724

ENST00000269878

103_138

115

188.0

Domain

EF-hand 2

Tgene

CIB3

chr19:10488890

chr19:16275724

ENST00000269878

66_101

115

188.0

Domain

EF-hand 1

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Fusion Gene Sequence for TYK2-CIB3

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.

>95650_95650_1_TYK2-CIB3_TYK2_chr19_10488890_ENST00000525621_CIB3_chr19_16275724_ENST00000269878_length(transcript)=990nt_BP=675nt
AAAAAAAAAAAAATCCAATGGTGACGAGCAGGGAGAACAGAGCAGCTGCCAATGGGCGTGTGCGTTTCAGGCGGCCAATGGGAGGAGGCG
TCTCGGCGGGGGACAAGCAGTAGCTACCCGCGGGAGCGGGGAGGGGTCCGGGTTCGAGCTTGTGTTCCCCCGGAAGGGTGAGTCTGGACG
CGGGCGCGGAAGGAGCGCGGCCGGAGGTCCTCAGGAAGAAGCCGCGGGGACTGGCTGCGCTTGACAGGCTGCACTTGGATGGGAGCACCT
GGTGCCTCGGGACTGCTCCGATGCCCGGGTCTGTGCTGAATGTGTAATATGCGGAACTATATTGAAACATTACAACCATCTTTTGATGGC
AACACCCTGAGGACCTCCCTTTTCCAGATGGGGAAACTGAGGCCCAGAATTGCTAAGTGGCTTGCTTGAGTTGACACAGGGAGCTCCAGG
ACTCACCCTCAGCTGAGCCACCTGCCGGGAGCATGCCTCTGCGCCACTGGGGGATGGCCAGGGGCAGTAAGCCCGTTGGGGATGGAGCCC
AGCCCATGGCTGCCATGGGAGGCCTGAAGGTGCTTCTGCACTGGGCTGGTCCAGGCGGCGGGGAGCCCTGGGTCACTTTCAGTGAGTCAT
CGCTGACAGCTGAGGAAGTCTGCATCCACATTGCACATAAAGTTGATTTTAACAACGACGACTACATTTGTGCGTGGGACCTGGAGCAGA
CGGTGACCAAACTGACGCGGGGGGGGCTGAGTGCCGAGGAGGTGAGCCTGGTATGTGAGAAGGTGCTGGATGAGGCTGATGGAGACCATG
ATGGGCGGCTGTCCCTGGAAGATTTCCAGAACATGATCCTCCGGGCACCAGACTTCCTCAGCACCTTCCACATCCGAATCTGATGGCACC
ACAGAGGAGCCGAGCTATAGGAGGGCGGGGTGACCCCTCACCCGCTGTGGACTCTGGTTTCTGAGAATAAACACAAGTCACTGAGTCACA

>95650_95650_1_TYK2-CIB3_TYK2_chr19_10488890_ENST00000525621_CIB3_chr19_16275724_ENST00000269878_length(amino acids)=136AA_BP=64
MPLRHWGMARGSKPVGDGAQPMAAMGGLKVLLHWAGPGGGEPWVTFSESSLTAEEVCIHIAHKVDFNNDDYICAWDLEQTVTKLTRGGLS

--------------------------------------------------------------
>95650_95650_2_TYK2-CIB3_TYK2_chr19_10488890_ENST00000525621_CIB3_chr19_16275724_ENST00000379859_length(transcript)=943nt_BP=675nt
AAAAAAAAAAAAATCCAATGGTGACGAGCAGGGAGAACAGAGCAGCTGCCAATGGGCGTGTGCGTTTCAGGCGGCCAATGGGAGGAGGCG
TCTCGGCGGGGGACAAGCAGTAGCTACCCGCGGGAGCGGGGAGGGGTCCGGGTTCGAGCTTGTGTTCCCCCGGAAGGGTGAGTCTGGACG
CGGGCGCGGAAGGAGCGCGGCCGGAGGTCCTCAGGAAGAAGCCGCGGGGACTGGCTGCGCTTGACAGGCTGCACTTGGATGGGAGCACCT
GGTGCCTCGGGACTGCTCCGATGCCCGGGTCTGTGCTGAATGTGTAATATGCGGAACTATATTGAAACATTACAACCATCTTTTGATGGC
AACACCCTGAGGACCTCCCTTTTCCAGATGGGGAAACTGAGGCCCAGAATTGCTAAGTGGCTTGCTTGAGTTGACACAGGGAGCTCCAGG
ACTCACCCTCAGCTGAGCCACCTGCCGGGAGCATGCCTCTGCGCCACTGGGGGATGGCCAGGGGCAGTAAGCCCGTTGGGGATGGAGCCC
AGCCCATGGCTGCCATGGGAGGCCTGAAGGTGCTTCTGCACTGGGCTGGTCCAGGCGGCGGGGAGCCCTGGGTCACTTTCAGTGAGTCAT
CGCTGACAGCTGAGGAAGTCTGCATCCACATTGCACATAAAGTTGATTTTAACAACGACGACTACATTTGTGCGTGGGACCTGGAGCAGA
CGGTGACCAAACTGACGCGGGGGGGGCTGAGTGCCGAGGAGGTGAGCCTGGTATGTGAGAAGGTGCTGGATGAGGCTGATGGAGACCATG
ATGGGCGGCTGTCCCTGGAAGATTTCCAGAACATGATCCTCCGGGCACCAGACTTCCTCAGCACCTTCCACATCCGAATCTGATGGCACC

>95650_95650_2_TYK2-CIB3_TYK2_chr19_10488890_ENST00000525621_CIB3_chr19_16275724_ENST00000379859_length(amino acids)=136AA_BP=64
MPLRHWGMARGSKPVGDGAQPMAAMGGLKVLLHWAGPGGGEPWVTFSESSLTAEEVCIHIAHKVDFNNDDYICAWDLEQTVTKLTRGGLS

--------------------------------------------------------------
>95650_95650_3_TYK2-CIB3_TYK2_chr19_10488890_ENST00000529370_CIB3_chr19_16275724_ENST00000269878_length(transcript)=839nt_BP=524nt
GTGTTCCCCCGGAAGGGTGAGTCTGGACGCGGGCGCGGAAGGAGCGCGGCCGGAGGTCCTCAGGAAGAAGCCGCGGGGACTGGCTGCGCT
TGACAGGCTGCACTTGGATGGGAGCACCTGGTGCCTCGGGACTGCTCCGATGCCCGGGTCTGTGCTGAATGTGTAATATGCGGAACTATA
TTGAAACATTACAACCATCTTTTGATGGCAACACCCTGAGGACCTCCCTTTTCCAGATGGGGAAACTGAGGCCCAGAATTGCTAAGTGGC
TTGCTTGAGTTGACACAGGGAGCTCCAGGACTCACCCTCAGCTGAGCCACCTGCCGGGAGCATGCCTCTGCGCCACTGGGGGATGGCCAG
GGGCAGTAAGCCCGTTGGGGATGGAGCCCAGCCCATGGCTGCCATGGGAGGCCTGAAGGTGCTTCTGCACTGGGCTGGTCCAGGCGGCGG
GGAGCCCTGGGTCACTTTCAGTGAGTCATCGCTGACAGCTGAGGAAGTCTGCATCCACATTGCACATAAAGTTGATTTTAACAACGACGA
CTACATTTGTGCGTGGGACCTGGAGCAGACGGTGACCAAACTGACGCGGGGGGGGCTGAGTGCCGAGGAGGTGAGCCTGGTATGTGAGAA
GGTGCTGGATGAGGCTGATGGAGACCATGATGGGCGGCTGTCCCTGGAAGATTTCCAGAACATGATCCTCCGGGCACCAGACTTCCTCAG
CACCTTCCACATCCGAATCTGATGGCACCACAGAGGAGCCGAGCTATAGGAGGGCGGGGTGACCCCTCACCCGCTGTGGACTCTGGTTTC

>95650_95650_3_TYK2-CIB3_TYK2_chr19_10488890_ENST00000529370_CIB3_chr19_16275724_ENST00000269878_length(amino acids)=136AA_BP=64
MPLRHWGMARGSKPVGDGAQPMAAMGGLKVLLHWAGPGGGEPWVTFSESSLTAEEVCIHIAHKVDFNNDDYICAWDLEQTVTKLTRGGLS

--------------------------------------------------------------
>95650_95650_4_TYK2-CIB3_TYK2_chr19_10488890_ENST00000529370_CIB3_chr19_16275724_ENST00000379859_length(transcript)=792nt_BP=524nt
GTGTTCCCCCGGAAGGGTGAGTCTGGACGCGGGCGCGGAAGGAGCGCGGCCGGAGGTCCTCAGGAAGAAGCCGCGGGGACTGGCTGCGCT
TGACAGGCTGCACTTGGATGGGAGCACCTGGTGCCTCGGGACTGCTCCGATGCCCGGGTCTGTGCTGAATGTGTAATATGCGGAACTATA
TTGAAACATTACAACCATCTTTTGATGGCAACACCCTGAGGACCTCCCTTTTCCAGATGGGGAAACTGAGGCCCAGAATTGCTAAGTGGC
TTGCTTGAGTTGACACAGGGAGCTCCAGGACTCACCCTCAGCTGAGCCACCTGCCGGGAGCATGCCTCTGCGCCACTGGGGGATGGCCAG
GGGCAGTAAGCCCGTTGGGGATGGAGCCCAGCCCATGGCTGCCATGGGAGGCCTGAAGGTGCTTCTGCACTGGGCTGGTCCAGGCGGCGG
GGAGCCCTGGGTCACTTTCAGTGAGTCATCGCTGACAGCTGAGGAAGTCTGCATCCACATTGCACATAAAGTTGATTTTAACAACGACGA
CTACATTTGTGCGTGGGACCTGGAGCAGACGGTGACCAAACTGACGCGGGGGGGGCTGAGTGCCGAGGAGGTGAGCCTGGTATGTGAGAA
GGTGCTGGATGAGGCTGATGGAGACCATGATGGGCGGCTGTCCCTGGAAGATTTCCAGAACATGATCCTCCGGGCACCAGACTTCCTCAG

>95650_95650_4_TYK2-CIB3_TYK2_chr19_10488890_ENST00000529370_CIB3_chr19_16275724_ENST00000379859_length(amino acids)=136AA_BP=64
MPLRHWGMARGSKPVGDGAQPMAAMGGLKVLLHWAGPGGGEPWVTFSESSLTAEEVCIHIAHKVDFNNDDYICAWDLEQTVTKLTRGGLS

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

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Fusion Gene PPI Analysis for TYK2-CIB3

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

- 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 TYK2-CIB3

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 TYK2-CIB3

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source