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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:ITCH-KCNT2 (FusionGDB2 ID:HG83737TG343450)

Fusion Gene Summary for ITCH-KCNT2

check button Fusion gene summary
Fusion gene informationFusion gene name: ITCH-KCNT2
Fusion gene ID: hg83737tg343450
HgeneTgene
Gene symbol

ITCH

KCNT2

Gene ID

83737

343450

Gene nameitchy E3 ubiquitin protein ligasepotassium sodium-activated channel subfamily T member 2
SynonymsADMFD|AIF4|AIP4|NAPP1EIEE57|KCa4.2|SLICK|SLO2.1
Cytomap('ITCH')('KCNT2')

20q11.22

1q31.3

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase Itchy homologHECT-type E3 ubiquitin transferase Itchy homologNFE2-associated polypeptide 1atrophin-1 interacting protein 4itchy E3 ubiquitin protein ligase homologpotassium channel subfamily T member 2potassium channel, subfamily T, member 2sequence like an intermediate conductance potassium channel subunitsodium and chloride-activated ATP-sensitive potassium channel Slo2.1sodium-and chloride-activated ATP-sens
Modification date2020032920200322
UniProtAcc

Q96J02

.
Ensembl transtripts involved in fusion geneENST00000262650, ENST00000374864, 
ENST00000535650, ENST00000483727, 
Fusion gene scores* DoF score27 X 16 X 18=77767 X 6 X 5=210
# samples 447
** MAII scorelog2(44/7776*10)=-4.14345279008112
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/210*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: ITCH [Title/Abstract] AND KCNT2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointITCH(32981687)-KCNT2(196227624), # samples:1
Anticipated loss of major functional domain due to fusion event.ITCH-KCNT2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
ITCH-KCNT2 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
HgeneITCH

GO:0006511

ubiquitin-dependent protein catabolic process

15678106

HgeneITCH

GO:0016567

protein ubiquitination

17592138|25631046

HgeneITCH

GO:0035519

protein K29-linked ubiquitination

17028573|18628966

HgeneITCH

GO:0070534

protein K63-linked ubiquitination

18718448|19592251

HgeneITCH

GO:0070936

protein K48-linked ubiquitination

19881509



check button Fusion gene information
* 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-8365-01AITCHchr20

32981687

+KCNT2chr1

196227624

-


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Fusion Gene ORF analysis for ITCH-KCNT2

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-3UTRENST00000262650ENST00000294725ITCHchr20

32981687

+KCNT2chr1

196227624

-
5CDS-3UTRENST00000262650ENST00000451324ITCHchr20

32981687

+KCNT2chr1

196227624

-
5CDS-3UTRENST00000374864ENST00000294725ITCHchr20

32981687

+KCNT2chr1

196227624

-
5CDS-3UTRENST00000374864ENST00000451324ITCHchr20

32981687

+KCNT2chr1

196227624

-
5CDS-5UTRENST00000262650ENST00000367431ITCHchr20

32981687

+KCNT2chr1

196227624

-
5CDS-5UTRENST00000262650ENST00000498426ITCHchr20

32981687

+KCNT2chr1

196227624

-
5CDS-5UTRENST00000262650ENST00000609185ITCHchr20

32981687

+KCNT2chr1

196227624

-
5CDS-5UTRENST00000374864ENST00000367431ITCHchr20

32981687

+KCNT2chr1

196227624

-
5CDS-5UTRENST00000374864ENST00000498426ITCHchr20

32981687

+KCNT2chr1

196227624

-
5CDS-5UTRENST00000374864ENST00000609185ITCHchr20

32981687

+KCNT2chr1

196227624

-
5UTR-3CDSENST00000535650ENST00000367433ITCHchr20

32981687

+KCNT2chr1

196227624

-
5UTR-3UTRENST00000535650ENST00000294725ITCHchr20

32981687

+KCNT2chr1

196227624

-
5UTR-3UTRENST00000535650ENST00000451324ITCHchr20

32981687

+KCNT2chr1

196227624

-
5UTR-5UTRENST00000535650ENST00000367431ITCHchr20

32981687

+KCNT2chr1

196227624

-
5UTR-5UTRENST00000535650ENST00000498426ITCHchr20

32981687

+KCNT2chr1

196227624

-
5UTR-5UTRENST00000535650ENST00000609185ITCHchr20

32981687

+KCNT2chr1

196227624

-
Frame-shiftENST00000262650ENST00000367433ITCHchr20

32981687

+KCNT2chr1

196227624

-
Frame-shiftENST00000374864ENST00000367433ITCHchr20

32981687

+KCNT2chr1

196227624

-
intron-3CDSENST00000483727ENST00000367433ITCHchr20

32981687

+KCNT2chr1

196227624

-
intron-3UTRENST00000483727ENST00000294725ITCHchr20

32981687

+KCNT2chr1

196227624

-
intron-3UTRENST00000483727ENST00000451324ITCHchr20

32981687

+KCNT2chr1

196227624

-
intron-5UTRENST00000483727ENST00000367431ITCHchr20

32981687

+KCNT2chr1

196227624

-
intron-5UTRENST00000483727ENST00000498426ITCHchr20

32981687

+KCNT2chr1

196227624

-
intron-5UTRENST00000483727ENST00000609185ITCHchr20

32981687

+KCNT2chr1

196227624

-

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 ITCH-KCNT2


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)


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Fusion Protein Features for ITCH-KCNT2


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/:32981687/:196227624)
- 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
ITCH

Q96J02

.
FUNCTION: Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:14602072, PubMed:17028573, PubMed:16387660, PubMed:18718448, PubMed:18718449, PubMed:11046148, PubMed:19592251, PubMed:19116316, PubMed:19881509, PubMed:20491914, PubMed:20392206, PubMed:20068034, PubMed:23146885, PubMed:24790097, PubMed:25631046). Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (PubMed:17028573, PubMed:18718448, PubMed:19131965, PubMed:19881509). Involved in the control of inflammatory signaling pathways (PubMed:19131965). Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (PubMed:19131965). Promotes the association of the complex after TNF stimulation (PubMed:19131965). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:19131965). This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 (PubMed:19131965). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (PubMed:19592251). Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response (PubMed:18718448, PubMed:20491914). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (PubMed:18718448). Mediates JUN ubiquitination and degradation (By similarity). Mediates JUNB ubiquitination and degradation (PubMed:16387660). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (By similarity). Involved in the negative regulation of MAVS-dependent cellular antiviral responses (PubMed:19881509). Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation (PubMed:19881509). Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity (PubMed:23146885). Ubiquitinates PI4K2A and negatively regulates its catalytic activity (PubMed:23146885). Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:14602072, PubMed:23146885). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination (PubMed:17028573, PubMed:18628966, PubMed:23886940). Ubiquitinates SNX9 (PubMed:20491914). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (By similarity). Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP (PubMed:20068034). Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Inhibits the replication of influenza A virus (IAV) via ubiquitination of IAV matrix protein 1 (M1) through 'Lys-48'-linked conjugation resulting in M1 proteasomal degradation (PubMed:30328013). {ECO:0000250|UniProtKB:Q8C863, ECO:0000269|PubMed:14602072, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:17028573, ECO:0000269|PubMed:18628966, ECO:0000269|PubMed:18718448, ECO:0000269|PubMed:18718449, ECO:0000269|PubMed:19116316, ECO:0000269|PubMed:19131965, ECO:0000269|PubMed:19592251, ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:20068034, ECO:0000269|PubMed:20392206, ECO:0000269|PubMed:20491914, ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:23886940, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:30328013}.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}.

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 ITCH-KCNT2


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 ITCH-KCNT2


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 ITCH-KCNT2


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 ITCH-KCNT2


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneITCHC3150649AUTOIMMUNE DISEASE, MULTISYSTEM, WITH FACIAL DYSMORPHISM2CTD_human;GENOMICS_ENGLAND;ORPHANET
HgeneITCHC4755273Syndromic multisystem autoimmune disease due to ITCH deficiency1GENOMICS_ENGLAND
TgeneC4540411EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 572GENOMICS_ENGLAND;UNIPROT
TgeneC0014544Epilepsy1GENOMICS_ENGLAND