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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:CRK-ARNTL (FusionGDB2 ID:19481)

Fusion Gene Summary for CRK-ARNTL

check button Fusion gene summary
Fusion gene informationFusion gene name: CRK-ARNTL
Fusion gene ID: 19481
HgeneTgene
Gene symbol

CRK

ARNTL

Gene ID

1398

406

Gene nameCRK proto-oncogene, adaptor proteinaryl hydrocarbon receptor nuclear translocator like
SynonymsCRKII|p38BMAL1|BMAL1c|JAP3|MOP3|PASD3|TIC|bHLHe5
Cytomap

17p13.3

11p15.3

Type of geneprotein-codingprotein-coding
Descriptionadapter molecule crkproto-oncogene c-Crkv-crk avian sarcoma virus CT10 oncogene homologv-crk sarcoma virus CT10 oncogene-like proteinaryl hydrocarbon receptor nuclear translocator-like protein 1ARNT-like protein 1, brain and musclePAS domain containing 3PAS domain-containing protein 3bHLH-PAS protein JAP3basic helix-loop-helix family member e5basic-helix-loop-helix-PAS orphan MOP
Modification date2020032720200322
UniProtAcc.

Q8WYA1

Ensembl transtripts involved in fusion geneENST00000300574, ENST00000398970, 
ENST00000572145, ENST00000574295, 
ENST00000361003, ENST00000389707, 
ENST00000389708, ENST00000396441, 
ENST00000401424, ENST00000403290, 
ENST00000403482, ENST00000403510, 
ENST00000497429, 
Fusion gene scores* DoF score15 X 11 X 7=11556 X 7 X 5=210
# samples 188
** MAII scorelog2(18/1155*10)=-2.68182403997375
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(8/210*10)=-1.39231742277876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: CRK [Title/Abstract] AND ARNTL [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointCRK(1349884)-ARNTL(13348819), # 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
HgeneCRK

GO:0009966

regulation of signal transduction

17515907

HgeneCRK

GO:0032956

regulation of actin cytoskeleton organization

11870224

HgeneCRK

GO:0043087

regulation of GTPase activity

11870224

HgeneCRK

GO:0048013

ephrin receptor signaling pathway

11870224

HgeneCRK

GO:0061045

negative regulation of wound healing

17515907

HgeneCRK

GO:2000146

negative regulation of cell motility

17515907

TgeneARNTL

GO:0032922

circadian regulation of gene expression

24005054

TgeneARNTL

GO:0045893

positive regulation of transcription, DNA-templated

11441146|12738229|23785138

TgeneARNTL

GO:0045944

positive regulation of transcription by RNA polymerase II

20093779

TgeneARNTL

GO:0051775

response to redox state

11441146


check buttonFusion gene breakpoints across CRK (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 ARNTL (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/ABE062150CRKchr17

1349884

+ARNTLchr11

13348819

-


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Fusion Gene ORF analysis for CRK-ARNTL

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-intronENST00000300574ENST00000361003CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000300574ENST00000389707CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000300574ENST00000389708CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000300574ENST00000396441CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000300574ENST00000401424CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000300574ENST00000403290CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000300574ENST00000403482CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000300574ENST00000403510CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000300574ENST00000497429CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000398970ENST00000361003CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000398970ENST00000389707CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000398970ENST00000389708CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000398970ENST00000396441CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000398970ENST00000401424CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000398970ENST00000403290CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000398970ENST00000403482CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000398970ENST00000403510CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000398970ENST00000497429CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000572145ENST00000361003CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000572145ENST00000389707CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000572145ENST00000389708CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000572145ENST00000396441CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000572145ENST00000401424CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000572145ENST00000403290CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000572145ENST00000403482CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000572145ENST00000403510CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000572145ENST00000497429CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000574295ENST00000361003CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000574295ENST00000389707CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000574295ENST00000389708CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000574295ENST00000396441CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000574295ENST00000401424CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000574295ENST00000403290CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000574295ENST00000403482CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000574295ENST00000403510CRKchr17

1349884

+ARNTLchr11

13348819

-
intron-intronENST00000574295ENST00000497429CRKchr17

1349884

+ARNTLchr11

13348819

-

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 CRK-ARNTL


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 CRK-ARNTL


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/:1349884/:13348819)
- 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
.ARNTL

Q8WYA1

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 forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. {ECO:0000269|PubMed:11018023, ECO:0000269|PubMed:12738229, ECO:0000269|PubMed:14672706}.

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 CRK-ARNTL


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 CRK-ARNTL


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 CRK-ARNTL


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 CRK-ARNTL


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