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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:TYK2-ARRB2 (FusionGDB2 ID:94988)

Fusion Gene Summary for TYK2-ARRB2

check button Fusion gene summary
Fusion gene informationFusion gene name: TYK2-ARRB2
Fusion gene ID: 94988
HgeneTgene
Gene symbol

TYK2

ARRB2

Gene ID

7297

409

Gene nametyrosine kinase 2arrestin beta 2
SynonymsIMD35|JTK1ARB2|ARR2|BARR2
Cytomap

19p13.2

17p13.2

Type of geneprotein-codingprotein-coding
Descriptionnon-receptor tyrosine-protein kinase TYK2beta-arrestin-2arrestin 3non-visual arrestin-3
Modification date2020032920200313
UniProtAcc.

P32121

Ensembl transtripts involved in fusion geneENST00000264818, ENST00000524462, 
ENST00000525621, ENST00000529370, 
ENST00000529422, 		ENST00000269260, 
ENST00000574954, ENST00000570718, 
ENST00000346341, ENST00000572457, 
ENST00000381488, ENST00000412477, 
ENST00000575877, ENST00000571206, 
Fusion gene scores* DoF score13 X 11 X 8=11443 X 4 X 2=24
# samples 154
** MAII scorelog2(15/1144*10)=-2.93105264628251
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(4/24*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Context

PubMed: TYK2 [Title/Abstract] AND ARRB2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointTYK2(10472807)-ARRB2(4620996), # samples:1
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
TgeneARRB2

GO:0002031

G protein-coupled receptor internalization

10644702

TgeneARRB2

GO:0006366

transcription by RNA polymerase II

16820410

TgeneARRB2

GO:0007179

transforming growth factor beta receptor signaling pathway

12958365

TgeneARRB2

GO:0031397

negative regulation of protein ubiquitination

16378096

TgeneARRB2

GO:0031623

receptor internalization

12958365

TgeneARRB2

GO:0032088

negative regulation of NF-kappaB transcription factor activity

15125834|16378096

TgeneARRB2

GO:0060765

regulation of androgen receptor signaling pathway

19372219

TgeneARRB2

GO:0070374

positive regulation of ERK1 and ERK2 cascade

10644702


check buttonFusion 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.

check buttonFusion gene breakpoints across ARRB2 (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
ChiTaRS5.0N/ABI024982TYK2chr19

10472807

+ARRB2chr17

4620996

+


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Fusion Gene ORF analysis for TYK2-ARRB2

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
intron-3CDSENST00000264818ENST00000269260TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000264818ENST00000574954TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000264818ENST00000570718TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000264818ENST00000346341TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000264818ENST00000572457TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000264818ENST00000381488TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000264818ENST00000412477TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000264818ENST00000575877TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000264818ENST00000571206TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-3CDSENST00000524462ENST00000269260TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000524462ENST00000574954TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000524462ENST00000570718TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000524462ENST00000346341TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000524462ENST00000572457TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000524462ENST00000381488TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000524462ENST00000412477TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000524462ENST00000575877TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000524462ENST00000571206TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-3CDSENST00000525621ENST00000269260TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000525621ENST00000574954TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000525621ENST00000570718TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000525621ENST00000346341TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000525621ENST00000572457TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000525621ENST00000381488TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000525621ENST00000412477TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000525621ENST00000575877TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000525621ENST00000571206TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-3CDSENST00000529370ENST00000269260TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529370ENST00000574954TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000529370ENST00000570718TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000529370ENST00000346341TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529370ENST00000572457TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529370ENST00000381488TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529370ENST00000412477TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529370ENST00000575877TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529370ENST00000571206TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-3CDSENST00000529422ENST00000269260TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529422ENST00000574954TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000529422ENST00000570718TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-intronENST00000529422ENST00000346341TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529422ENST00000572457TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529422ENST00000381488TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529422ENST00000412477TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529422ENST00000575877TYK2chr19

10472807

+ARRB2chr17

4620996

+
intron-5UTRENST00000529422ENST00000571206TYK2chr19

10472807

+ARRB2chr17

4620996

+

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 TYK2-ARRB2


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 TYK2-ARRB2


check button Go to

FGviewer for the breakpoints of :-:

.
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
.ARRB2

P32121

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: Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors other than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which also requires GRK2. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Involved in insulin resistance by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in IL8-mediated granule release in neutrophils. Involved in the internalization of the atypical chemokine receptor ACKR3. Acts as an adapter protein coupling FFAR4 receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis (PubMed:22282525, PubMed:23809162). During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of proinflammatory cytokine release and inhibition of inflammation (PubMed:23809162). {ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:11877451, ECO:0000269|PubMed:12488444, ECO:0000269|PubMed:12582207, ECO:0000269|PubMed:12949261, ECO:0000269|PubMed:12958365, ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15054093, ECO:0000269|PubMed:15125834, ECO:0000269|PubMed:15205453, ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15618519, ECO:0000269|PubMed:15635042, ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15699339, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16280323, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667, ECO:0000269|PubMed:16820410, ECO:0000269|PubMed:17540773, ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:18604210, ECO:0000269|PubMed:19325136, ECO:0000269|PubMed:19620252, ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:20048153, ECO:0000269|PubMed:22282525, ECO:0000269|PubMed:22457824, ECO:0000269|PubMed:23809162}.

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 TYK2-ARRB2


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 TYK2-ARRB2


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 TYK2-ARRB2


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 TYK2-ARRB2


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneTYK2C1969086Tyrosine Kinase 2 Deficiency3CTD_human;GENOMICS_ENGLAND;ORPHANET
HgeneTYK2C0003873Rheumatoid Arthritis2CTD_human
HgeneTYK2C0008312Primary biliary cirrhosis1CTD_human
HgeneTYK2C0009171Cocaine Abuse1CTD_human
HgeneTYK2C0010346Crohn Disease1CTD_human;GENOMICS_ENGLAND
HgeneTYK2C0011854Diabetes Mellitus, Insulin-Dependent1CTD_human
HgeneTYK2C0023892Biliary cirrhosis1CTD_human
HgeneTYK2C0026769Multiple Sclerosis1CTD_human
HgeneTYK2C0030246Pustulosis of Palms and Soles1CTD_human
HgeneTYK2C0033860Psoriasis1CTD_human
HgeneTYK2C0041696Unipolar Depression1PSYGENET
HgeneTYK2C0156147Crohn's disease of large bowel1CTD_human
HgeneTYK2C0205734Diabetes, Autoimmune1CTD_human
HgeneTYK2C0206182Lymphomatoid Papulosis1ORPHANET
HgeneTYK2C0236736Cocaine-Related Disorders1CTD_human
HgeneTYK2C0238065Secondary Biliary Cholangitis1CTD_human
HgeneTYK2C0267380Crohn's disease of the ileum1CTD_human
HgeneTYK2C0342302Brittle diabetes1CTD_human
HgeneTYK2C0344315Depressed mood1PSYGENET
HgeneTYK2C0600427Cocaine Dependence1CTD_human
HgeneTYK2C0678202Regional enteritis1CTD_human
HgeneTYK2C0751324Multiple Sclerosis, Acute Fulminating1CTD_human
HgeneTYK2C0949272IIeocolitis1CTD_human
HgeneTYK2C1269683Major Depressive Disorder1PSYGENET
HgeneTYK2C1301362Primary Cutaneous Anaplastic Large Cell Lymphoma1ORPHANET
HgeneTYK2C1456784Paranoia1CTD_human
HgeneTYK2C1961099Precursor T-Cell Lymphoblastic Leukemia-Lymphoma1CTD_human
HgeneTYK2C3837958Diabetes Mellitus, Ketosis-Prone1CTD_human
HgeneTYK2C4551595Biliary Cirrhosis, Primary, 11CTD_human
HgeneTYK2C4554117Diabetes Mellitus, Sudden-Onset1CTD_human
TgeneARRB2C0005586Bipolar Disorder1PSYGENET
TgeneARRB2C0011570Mental Depression1PSYGENET
TgeneARRB2C0011581Depressive disorder1PSYGENET
TgeneARRB2C0023893Liver Cirrhosis, Experimental1CTD_human
TgeneARRB2C0236733Amphetamine-Related Disorders1CTD_human
TgeneARRB2C0236804Amphetamine Addiction1CTD_human
TgeneARRB2C0236807Amphetamine Abuse1CTD_human
TgeneARRB2C0525045Mood Disorders1PSYGENET