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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-CDC37 (FusionGDB2 ID:94989)

Fusion Gene Summary for TYK2-CDC37

Fusion gene summary

Fusion gene information	Fusion gene name: TYK2-CDC37
	Fusion gene ID: 94989
		Hgene	Tgene
	Gene symbol	TYK2	CDC37
	Gene ID	7297	11140
	Gene name	tyrosine kinase 2	cell division cycle 37, HSP90 cochaperone
	Synonyms	IMD35\|JTK1	P50CDC37
	Cytomap	19p13.2	19p13.2
	Type of gene	protein-coding	protein-coding
	Description	non-receptor tyrosine-protein kinase TYK2	hsp90 co-chaperone Cdc37CDC37 (cell division cycle 37, S. cerevisiae, homolog)CDC37 cell division cycle 37 homologcell division cycle 37 homologhsp90 chaperone protein kinase-targeting subunit
	Modification date	20200329	20200327
	UniProtAcc	.	Q7L3B6
	Ensembl transtripts involved in fusion gene	ENST00000264818, ENST00000524462, ENST00000525621, ENST00000529370, ENST00000529422,	ENST00000222005,
Fusion gene scores	* DoF score	13 X 11 X 8=1144	5 X 8 X 4=160
	# samples	15	7
	** MAII score	log2(15/1144*10)=-2.93105264628251 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(7/160*10)=-1.1926450779424 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context	PubMed: TYK2 [Title/Abstract] AND CDC37 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	TYK2(10488890)-CDC37(10504117), # samples:4 CDC37(10514054)-TYK2(10464910), # samples:1
Anticipated loss of major functional domain due to fusion event.	TYK2-CDC37 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. TYK2-CDC37 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. TYK2-CDC37 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 CDC37 (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	BRCA	TCGA-A2-A0D0-01A	TYK2	chr19	10488890	-	CDC37	chr19	10504117	-
ChimerDB4	PAAD	TCGA-HZ-7926-01A	TYK2	chr19	10488890	-	CDC37	chr19	10504117	-
ChimerDB4	BRCA	TCGA-A2-A0D0-01A	TYK2	chr19	10488890	-	CDC37	chr19	10504117	-
ChimerDB4	BRCA	TCGA-A2-A0D0-01A	TYK2	chr19	10490291	-	CDC37	chr19	10504117	-
ChimerDB4	BRCA	TCGA-A2-A0D0-01A	TYK2	chr19	10488890	-	CDC37	chr19	10504113	-
ChimerDB4	BRCA	TCGA-A2-A0D0-01A	TYK2	chr19	10488890	-	CDC37	chr19	10504117	-

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Fusion Gene ORF analysis for TYK2-CDC37

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	ENST00000264818	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504117	-
intron-3CDS	ENST00000524462	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504117	-
Frame-shift	ENST00000525621	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504117	-
Frame-shift	ENST00000529370	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504117	-
intron-3CDS	ENST00000529422	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504117	-
intron-3CDS	ENST00000264818	ENST00000222005	TYK2	chr19	10490291	-	CDC37	chr19	10504117	-
intron-3CDS	ENST00000524462	ENST00000222005	TYK2	chr19	10490291	-	CDC37	chr19	10504117	-
5UTR-3CDS	ENST00000525621	ENST00000222005	TYK2	chr19	10490291	-	CDC37	chr19	10504117	-
5UTR-3CDS	ENST00000529370	ENST00000222005	TYK2	chr19	10490291	-	CDC37	chr19	10504117	-
intron-3CDS	ENST00000529422	ENST00000222005	TYK2	chr19	10490291	-	CDC37	chr19	10504117	-
In-frame	ENST00000264818	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504113	-
intron-3CDS	ENST00000524462	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504113	-
Frame-shift	ENST00000525621	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504113	-
Frame-shift	ENST00000529370	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504113	-
intron-3CDS	ENST00000529422	ENST00000222005	TYK2	chr19	10488890	-	CDC37	chr19	10504113	-

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)

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

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Fusion Genomic Features for TYK2-CDC37

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-CDC37

Go to
FGviewer for the breakpoints of chr19:10488890-chr19:10504117
.
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.

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

Hgene	Tgene
.	CDC37 Q7L3B6
FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.	FUNCTION: Co-chaperone that binds to numerous proteins and promotes their interaction with Hsp70 and Hsp90. {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

- 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

chr19:10504113

ENST00000264818

26_431

64.33333333333333

1188.0

Domain

FERM

Hgene

TYK2

chr19:10488890

chr19:10504113

ENST00000264818

450_529

64.33333333333333

1188.0

Domain

Note=SH2%3B atypical

Hgene

TYK2

chr19:10488890

chr19:10504113

ENST00000264818

589_875

64.33333333333333

1188.0

Domain

Protein kinase 1

Hgene

TYK2

chr19:10488890

chr19:10504113

ENST00000264818

897_1176

64.33333333333333

1188.0

Domain

Protein kinase 2

Hgene

TYK2

chr19:10488890

chr19:10504113

ENST00000525621

26_431

64.33333333333333

1188.0

Domain

FERM

Hgene

TYK2

chr19:10488890

chr19:10504113

ENST00000525621

450_529

64.33333333333333

1188.0

Domain

Note=SH2%3B atypical

Hgene

TYK2

chr19:10488890

chr19:10504113

ENST00000525621

589_875

64.33333333333333

1188.0

Domain

Protein kinase 1

Hgene

TYK2

chr19:10488890

chr19:10504113

ENST00000525621

897_1176

64.33333333333333

1188.0

Domain

Protein kinase 2

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000264818

26_431

64.33333333333333

1188.0

Domain

FERM

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000264818

450_529

64.33333333333333

1188.0

Domain

Note=SH2%3B atypical

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000264818

589_875

64.33333333333333

1188.0

Domain

Protein kinase 1

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000264818

897_1176

64.33333333333333

1188.0

Domain

Protein kinase 2

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000525621

26_431

64.33333333333333

1188.0

Domain

FERM

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000525621

450_529

64.33333333333333

1188.0

Domain

Note=SH2%3B atypical

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000525621

589_875

64.33333333333333

1188.0

Domain

Protein kinase 1

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000525621

897_1176

64.33333333333333

1188.0

Domain

Protein kinase 2

Hgene

TYK2

chr19:10488890

chr19:10504113

ENST00000264818

903_911

64.33333333333333

1188.0

Nucleotide binding

ATP

Hgene

TYK2

chr19:10488890

chr19:10504113

ENST00000525621

903_911

64.33333333333333

1188.0

Nucleotide binding

ATP

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000264818

903_911

64.33333333333333

1188.0

Nucleotide binding

ATP

Hgene

TYK2

chr19:10488890

chr19:10504117

ENST00000525621

903_911

64.33333333333333

1188.0

Nucleotide binding

ATP

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Fusion Gene Sequence for TYK2-CDC37

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 TYK2-CDC37

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-CDC37

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-CDC37

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner	Gene	Disease ID	Disease name	# pubmeds	Source
Hgene	TYK2	C1969086	Tyrosine Kinase 2 Deficiency	3	CTD_human;GENOMICS_ENGLAND;ORPHANET
Hgene	TYK2	C0003873	Rheumatoid Arthritis	2	CTD_human
Hgene	TYK2	C0008312	Primary biliary cirrhosis	1	CTD_human
Hgene	TYK2	C0009171	Cocaine Abuse	1	CTD_human
Hgene	TYK2	C0010346	Crohn Disease	1	CTD_human;GENOMICS_ENGLAND
Hgene	TYK2	C0011854	Diabetes Mellitus, Insulin-Dependent	1	CTD_human
Hgene	TYK2	C0023892	Biliary cirrhosis	1	CTD_human
Hgene	TYK2	C0026769	Multiple Sclerosis	1	CTD_human
Hgene	TYK2	C0030246	Pustulosis of Palms and Soles	1	CTD_human
Hgene	TYK2	C0033860	Psoriasis	1	CTD_human
Hgene	TYK2	C0041696	Unipolar Depression	1	PSYGENET
Hgene	TYK2	C0156147	Crohn's disease of large bowel	1	CTD_human
Hgene	TYK2	C0205734	Diabetes, Autoimmune	1	CTD_human
Hgene	TYK2	C0206182	Lymphomatoid Papulosis	1	ORPHANET
Hgene	TYK2	C0236736	Cocaine-Related Disorders	1	CTD_human
Hgene	TYK2	C0238065	Secondary Biliary Cholangitis	1	CTD_human
Hgene	TYK2	C0267380	Crohn's disease of the ileum	1	CTD_human
Hgene	TYK2	C0342302	Brittle diabetes	1	CTD_human
Hgene	TYK2	C0344315	Depressed mood	1	PSYGENET
Hgene	TYK2	C0600427	Cocaine Dependence	1	CTD_human
Hgene	TYK2	C0678202	Regional enteritis	1	CTD_human
Hgene	TYK2	C0751324	Multiple Sclerosis, Acute Fulminating	1	CTD_human
Hgene	TYK2	C0949272	IIeocolitis	1	CTD_human
Hgene	TYK2	C1269683	Major Depressive Disorder	1	PSYGENET
Hgene	TYK2	C1301362	Primary Cutaneous Anaplastic Large Cell Lymphoma	1	ORPHANET
Hgene	TYK2	C1456784	Paranoia	1	CTD_human
Hgene	TYK2	C1961099	Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	1	CTD_human
Hgene	TYK2	C3837958	Diabetes Mellitus, Ketosis-Prone	1	CTD_human
Hgene	TYK2	C4551595	Biliary Cirrhosis, Primary, 1	1	CTD_human
Hgene	TYK2	C4554117	Diabetes Mellitus, Sudden-Onset	1	CTD_human