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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:CASC3-CDK12 (FusionGDB2 ID:13145)

Fusion Gene Summary for CASC3-CDK12

check button Fusion gene summary
Fusion gene informationFusion gene name: CASC3-CDK12
Fusion gene ID: 13145
HgeneTgene
Gene symbol

CASC3

CDK12

Gene ID

22794

51755

Gene nameCASC3 exon junction complex subunitcyclin dependent kinase 12
SynonymsBTZ|MLN51CRK7|CRKR|CRKRS
Cytomap

17q21.1

17q12

Type of geneprotein-codingprotein-coding
Descriptionprotein CASC3MLN 51barentszcancer susceptibility 3cancer susceptibility candidate 3cancer susceptibility candidate gene 3 proteinmetastatic lymph node 51metastatic lymph node gene 51 proteinprotein barentszcyclin-dependent kinase 12CDC2-related protein kinase 7Cdc2-related kinase, arginine/serine-richcell division cycle 2-related protein kinase 7cell division protein kinase 12
Modification date2020031320200313
UniProtAcc

O15234

Q9NYV4

Ensembl transtripts involved in fusion geneENST00000264645, ENST00000559545, 
ENST00000430627, ENST00000447079, 
Fusion gene scores* DoF score21 X 10 X 10=210036 X 30 X 14=15120
# samples 2855
** MAII scorelog2(28/2100*10)=-2.90689059560852
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(55/15120*10)=-4.78088271069641
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: CASC3 [Title/Abstract] AND CDK12 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointCASC3(38297860)-CDK12(37680926), # samples:1
CASC3(38297860)-CDK12(37680927), # samples:1
CASC3(38297860)-CDK12(37686884), # samples:1
Anticipated loss of major functional domain due to fusion event.CASC3-CDK12 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
CASC3-CDK12 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CASC3-CDK12 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
CASC3-CDK12 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
CASC3-CDK12 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
CASC3-CDK12 seems lost the major protein functional domain in Tgene partner, which is a kinase 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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCASC3

GO:0000398

mRNA splicing, via spliceosome

29301961

TgeneCDK12

GO:0046777

protein autophosphorylation

11683387


check buttonFusion gene breakpoints across CASC3 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across CDK12 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

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
ChimerDB4STADTCGA-BR-4366-01ACASC3chr17

38297860

-CDK12chr17

37686884

+
ChimerDB4STADTCGA-CD-A486-01ACASC3chr17

38297860

+CDK12chr17

37680927

+
ChimerDB4STADTCGA-CD-A486CASC3chr17

38297860

+CDK12chr17

37680926

+


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Fusion Gene ORF analysis for CASC3-CDK12

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
5CDS-intronENST00000264645ENST00000559545CASC3chr17

38297860

-CDK12chr17

37686884

+
5CDS-intronENST00000264645ENST00000559545CASC3chr17

38297860

+CDK12chr17

37680927

+
5CDS-intronENST00000264645ENST00000559545CASC3chr17

38297860

+CDK12chr17

37680926

+
Frame-shiftENST00000264645ENST00000430627CASC3chr17

38297860

+CDK12chr17

37680927

+
Frame-shiftENST00000264645ENST00000430627CASC3chr17

38297860

+CDK12chr17

37680926

+
Frame-shiftENST00000264645ENST00000447079CASC3chr17

38297860

-CDK12chr17

37686884

+
Frame-shiftENST00000264645ENST00000447079CASC3chr17

38297860

+CDK12chr17

37680927

+
Frame-shiftENST00000264645ENST00000447079CASC3chr17

38297860

+CDK12chr17

37680926

+
In-frameENST00000264645ENST00000430627CASC3chr17

38297860

-CDK12chr17

37686884

+

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)
ENST00000264645CASC3chr1738297860-ENST00000430627CDK12chr1737686884+23705235761208210

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
ENST00000264645ENST00000430627CASC3chr1738297860-CDK12chr1737686884+0.1044450250.89555496

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Fusion Genomic Features for CASC3-CDK12


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)
CASC3chr1738297860+CDK12chr1737680926+2.18E-101
CASC3chr1738297860+CDK12chr1737680926+2.18E-101
CASC3chr1738297860+CDK12chr1737680926+2.18E-101
CASC3chr1738297860+CDK12chr1737680926+2.18E-101

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.
genomic feature

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.
genomic feature of top 1%

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Fusion Protein Features for CASC3-CDK12


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/chr17:38297860/chr17:37680926)
- 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
CASC3

O15234

CDK12

Q9NYV4

FUNCTION: Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homopolymer. {ECO:0000269|PubMed:17375189, ECO:0000269|PubMed:17652158, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961}.FUNCTION: Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}.

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
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-31441_46991130.6666666666667Compositional biasNote=Poly-Gly
TgeneCDK12chr17:38297860chr17:37686884ENST0000043062712141266_128012531482.0Compositional biasNote=Poly-Pro
TgeneCDK12chr17:38297860chr17:37686884ENST000004470790141266_128001491.0Compositional biasNote=Poly-Pro
TgeneCDK12chr17:38297860chr17:37686884ENST00000447079014407_41301491.0Compositional biasNote=Poly-Ala
TgeneCDK12chr17:38297860chr17:37686884ENST00000447079014535_54001491.0Compositional biasNote=Poly-Pro
TgeneCDK12chr17:38297860chr17:37686884ENST00000447079014727_102001491.0DomainProtein kinase
TgeneCDK12chr17:38297860chr17:37686884ENST00000447079014733_74101491.0Nucleotide bindingNote=ATP
TgeneCDK12chr17:38297860chr17:37686884ENST00000447079014814_81901491.0Nucleotide bindingNote=ATP

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-31495_131991130.6666666666667Coiled coilOntology_term=ECO:0000255
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-314392_395991130.6666666666667Compositional biasNote=Poly-Pro
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-314425_428991130.6666666666667Compositional biasNote=Poly-Pro
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-314643_648991130.6666666666667Compositional biasNote=Poly-Pro
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-314692_695991130.6666666666667Compositional biasNote=Poly-Pro
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-314204_210991130.6666666666667MotifNuclear localization signal 1
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-314254_262991130.6666666666667MotifNuclear localization signal 2
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-314462_466991130.6666666666667MotifNote=Nuclear export signal
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-314137_283991130.6666666666667RegionNote=Sufficient to form the EJC
HgeneCASC3chr17:38297860chr17:37686884ENST00000264645-314377_703991130.6666666666667RegionNote=Necessary for localization in cytoplasmic stress granules
TgeneCDK12chr17:38297860chr17:37686884ENST000004306271214407_41312531482.0Compositional biasNote=Poly-Ala
TgeneCDK12chr17:38297860chr17:37686884ENST000004306271214535_54012531482.0Compositional biasNote=Poly-Pro
TgeneCDK12chr17:38297860chr17:37686884ENST000004306271214727_102012531482.0DomainProtein kinase
TgeneCDK12chr17:38297860chr17:37686884ENST000004306271214733_74112531482.0Nucleotide bindingNote=ATP
TgeneCDK12chr17:38297860chr17:37686884ENST000004306271214814_81912531482.0Nucleotide bindingNote=ATP


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Fusion Gene Sequence for CASC3-CDK12


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.
>13145_13145_1_CASC3-CDK12_CASC3_chr17_38297860_ENST00000264645_CDK12_chr17_37686884_ENST00000430627_length(transcript)=2370nt_BP=523nt
CACACACACACACACACACACACACACCCCAACACACACACACACACCCCAACACACACACACACACACACACACACACACACACACACA
CACACACACACACACACAGCGGGATGGCCGAGCGCCGCACGCGTAGCACGCCGGGACTAGCTATCCAGCCTCCCAGCAGCCTCTGCGACG
GGCGCGGTGCGTAAGTACCTCGCCGGTGGTGGCCGTTCTCCGTAAGATGGCGGACCGGCGGCGGCAGCGCGCTTCGCAAGACACCGAGGA
CGAGGAATCTGGTGCTTCGGGCTCCGACAGCGGCGGCTCCCCGTTGCGGGGAGGCGGGAGCTGCAGCGGTAGCGCCGGAGGCGGCGGCAG
CGGCTCTCTGCCTTCACAGCGCGGAGGCCGAACCGGGGCCCTTCATCTGCGGCGGGTGGAGAGCGGGGGCGCCAAGAGTGCTGAGGAGTC
GGAGTGTGAGAGTGAAGATGGCATTGAAGGTGATGCTGTTCTCTCGGATTATGAAAGTGCAGAAGACTCGGAAAGAAGAGGCCCCCTGAG
CCCCCCGGACCTCCACCGCCGCCACCTCCACCCCCTCTGGTTGAAGGCGATCTTTCCAGCGCCCCCCAGGAGTTGAACCCAGCCGTGACA
GCCGCCTTGCTGCAACTTTTATCCCAGCCTGAAGCAGAGCCTCCTGGCCACCTGCCACATGAGCACCAGGCCTTGAGACCAATGGAGTAC
TCCACCCGACCCCGTCCAAACAGGACTTATGGAAACACTGATGGGCCTGAAACAGGGTTCAGTGCCATTGACACTGATGAACGAAACTCT
GGTCCAGCCTTGACAGAATCCTTGGTCCAGACCCTGGTGAAGAACAGGACCTTCTCAGGCTCTCTGAGCCACCTTGGGGAGTCCAGCAGT
TACCAGGGCACAGGGTCAGTGCAGTTTCCAGGGGACCAGGACCTCCGTTTTGCCAGGGTCCCCTTAGCGTTACACCCGGTGGTCGGGCAA
CCATTCCTGAAGGCTGAGGGAAGCAGCAATTCTGTGGTACATGCAGAGACCAAATTGCAAAACTATGGGGAGCTGGGGCCAGGAACCACT
GGGGCCAGCAGCTCAGGAGCAGGCCTTCACTGGGGGGGCCCAACTCAGTCTTCTGCTTATGGAAAACTCTATCGGGGGCCTACAAGAGTC
CCACCAAGAGGGGGAAGAGGGAGAGGAGTTCCTTACTAACCCAGAGACTTCAGTGTCCTGAAAGATTCCTTTCCTATCCATCCTTCCATC
CAGTTCTCTGAATCTTTAATGAAATCATTTGCCAGAGCGAGGTAATCATCTGCATTTGGCTACTGCAAAGCTGTCCGTTGTATTCCTTGC
TCACTTGCTACTAGCAGGCGACTTACGAAATAATGATGTTGGCACCAGTTCCCCCTGGATGGGCTATAGCCAGAACATTTACTTCAACTC
TACCTTAGTAGATACAAGTAGAGAATATGGAGAGGATCATTACATTGAAAAGTAAATGTTTTATTAGTTCATTGCCTGCACTTACTGATC
GGAAGAGAGAAAGAACAGTTTCAGTATTGAGATGGCTCAGGAGAGGCTCTTTGATTTTTAAAGTTTTGGGGTGGGGGATTGTGTGTGGTT
TCTTTCTTTTGAATTTTAATTTAGGTGTTTTGGGTTTTTTTCCTTTAAAGAGAATAGTGTTCACAAAATTTGAGCTGCTCTTTGGCTTTT
GCTATAAGGGAAACAGAGTGGCCTGGCTGATTTGAATAAATGTTTCTTTCCTCTCCACCATCTCACATTTTGCTTTTAAGTGAACACTTT
TTCCCCATTGAGCATCTTGAACATACTTTTTTTCCAAATAAATTACTCATCCTTAAAGTTTACTCCACTTTGACAAAAGATACGCCCTTC
TCCCTGCACATAAAGCAGGTTGTAGAACGTGGCATTCTTGGGCAAGTAGGTAGACTTTACCCAGTCTCTTTCCTTTTTTGCTGATGTGTG
CTCTCTCTCTCTCTTTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTGTCTCGCTTGCTCGCTCTCGCTGTTTCTCTCTCT
TTGAGGCATTTGTTTGGAAAAAATCGTTGAGATGCCCAAGAACCTGGGATAATTCTTTACTTTTTTTGAAATAAAGGAAAGGAAATTCAG
ACTCTTACATTGTTCTCTGTAACTCTTCAATTCTAAAATGTTTTGTTTTTTAAACCATGTTCTGATGGGGAAGTTGATTTGTAAGTGTGG
ACAGCTTGGACATTGCTGCTGAGCTGTGGTTAGAGATGATGCCTCCATTCCTAGAGGGCTAATAACAGCATTTAGCATATTGTTTACACA

>13145_13145_1_CASC3-CDK12_CASC3_chr17_38297860_ENST00000264645_CDK12_chr17_37686884_ENST00000430627_length(amino acids)=210AA_BP=
MVEGDLSSAPQELNPAVTAALLQLLSQPEAEPPGHLPHEHQALRPMEYSTRPRPNRTYGNTDGPETGFSAIDTDERNSGPALTESLVQTL
VKNRTFSGSLSHLGESSSYQGTGSVQFPGDQDLRFARVPLALHPVVGQPFLKAEGSSNSVVHAETKLQNYGELGPGTTGASSSGAGLHWG

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Fusion Gene PPI Analysis for CASC3-CDK12


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 CASC3-CDK12


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 CASC3-CDK12


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