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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:KCNQ1-NCOR2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KCNQ1-NCOR2
FusionPDB ID: 41545
FusionGDB2.0 ID: 41545
HgeneTgene
Gene symbol

KCNQ1

NCOR2

Gene ID

3784

9612

Gene namepotassium voltage-gated channel subfamily Q member 1nuclear receptor corepressor 2
SynonymsATFB1|ATFB3|JLNS1|KCNA8|KCNA9|KVLQT1|Kv1.9|Kv7.1|LQT|LQT1|RWS|SQT2|WRSCTG26|N-CoR2|SMAP270|SMRT|SMRTE|SMRTE-tau|TNRC14|TRAC|TRAC-1|TRAC1
Cytomap

11p15.5-p15.4

12q24.31

Type of geneprotein-codingprotein-coding
Descriptionpotassium voltage-gated channel subfamily KQT member 1IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1kidney and cardiac voltage dependend K+ channelpotassium channel, voltage gated KQT-like subfamily Q, member 1potassium voltagnuclear receptor corepressor 2CTG repeat protein 26T3 receptor-associating factorsilencing mediator for retinoid and thyroid hormone receptorsthyroid-, retinoic-acid-receptor-associated corepressor
Modification date2020031320200313
UniProtAcc

P51787

Main function of 5'-partner protein: FUNCTION: Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:25441029). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568). {ECO:0000250|UniProtKB:P97414, ECO:0000250|UniProtKB:Q9Z0N7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:11101505, ECO:0000269|PubMed:12324418, ECO:0000269|PubMed:19687231, ECO:0000269|PubMed:24855057, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:8900283, ECO:0000269|PubMed:9108097, ECO:0000269|PubMed:9312006}.; FUNCTION: [Isoform 2]: Non-functional alone but modulatory when coexpressed with the full-length isoform 1. {ECO:0000269|PubMed:9305853}.

Q9Y618

Main function of 5'-partner protein: FUNCTION: Transcriptional corepressor (PubMed:20812024). Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 4 have different affinities for different nuclear receptors. Involved in the regulation BCL6-dependent of the germinal center (GC) reactions, mainly through the control of the GC B-cells proliferation and survival. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). {ECO:0000269|PubMed:18212045, ECO:0000269|PubMed:20812024, ECO:0000269|PubMed:23911289}.
Ensembl transtripts involved in fusion geneENST idsENST00000526095, ENST00000155840, 
ENST00000335475, 
ENST00000404621, 
ENST00000405201, ENST00000356219, 
ENST00000397355, ENST00000404121, 
ENST00000429285, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 12 X 11=250819 X 18 X 11=3762
# samples 2319
** MAII scorelog2(23/2508*10)=-3.44683158185766
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/3762*10)=-4.30742852519225
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KCNQ1 [Title/Abstract] AND NCOR2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KCNQ1 [Title/Abstract] AND NCOR2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NCOR2(124835132)-KCNQ1(2790073), # samples:1
NCOR2(124835133)-KCNQ1(2790074), # samples:1
KCNQ1(2799267)-NCOR2(124911346), # samples:1
Anticipated loss of major functional domain due to fusion event.KCNQ1-NCOR2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
KCNQ1-NCOR2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
KCNQ1-NCOR2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
KCNQ1-NCOR2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
NCOR2-KCNQ1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
NCOR2-KCNQ1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
NCOR2-KCNQ1 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
NCOR2-KCNQ1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
NCOR2-KCNQ1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
NCOR2-KCNQ1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NCOR2-KCNQ1 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
HgeneKCNQ1

GO:0035690

cellular response to drug

9108097

HgeneKCNQ1

GO:0060306

regulation of membrane repolarization

11299204

HgeneKCNQ1

GO:0071320

cellular response to cAMP

11299204|16002409

HgeneKCNQ1

GO:0071805

potassium ion transmembrane transport

9354802|11299204|16002409

HgeneKCNQ1

GO:0086011

membrane repolarization during action potential

8900283|11299204|19646991

HgeneKCNQ1

GO:0097623

potassium ion export across plasma membrane

8900283|10400998|17289006

HgeneKCNQ1

GO:1901381

positive regulation of potassium ion transmembrane transport

8900283



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/chr11:124835132/chr12:2790073)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across KCNQ1 (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 NCOR2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000155840KCNQ1chr112799267+ENST00000405201NCOR2chr12124911346-92851902982972762
ENST00000155840KCNQ1chr112799267+ENST00000404621NCOR2chr12124911346-91201902981322707
ENST00000335475KCNQ1chr112799267+ENST00000405201NCOR2chr12124911346-9070168727480822602
ENST00000335475KCNQ1chr112799267+ENST00000404621NCOR2chr12124911346-8905168727479172547

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
ENST00000155840ENST00000405201KCNQ1chr112799267+NCOR2chr12124911346-0.0068589850.993141
ENST00000155840ENST00000404621KCNQ1chr112799267+NCOR2chr12124911346-0.0066778980.9933221
ENST00000335475ENST00000405201KCNQ1chr112799267+NCOR2chr12124911346-0.0074175060.99258244
ENST00000335475ENST00000404621KCNQ1chr112799267+NCOR2chr12124911346-0.0072784620.9927215

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for KCNQ1-NCOR2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KCNQ1chr112799267NCOR2chr121249113461687471NTIGARLNRVEDKNLEKQMRQLAVIP
KCNQ1chr112799267NCOR2chr121249113461902631NTIGARLNRVEDKNLEKQMRQLAVIP

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Potential FusionNeoAntigen Information of KCNQ1-NCOR2 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
KCNQ1-NCOR2_2799267_124911346.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
KCNQ1-NCOR2chr112799267chr121249113461902HLA-A30:08RVEDKNLEK0.97780.722817
KCNQ1-NCOR2chr112799267chr121249113461902HLA-B39:08VEDKNLEKQM0.93660.8761919
KCNQ1-NCOR2chr112799267chr121249113461902HLA-A30:01RVEDKNLEK0.97830.8181817
KCNQ1-NCOR2chr112799267chr121249113461902HLA-B41:03VEDKNLEKQM0.67410.5023919

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Potential FusionNeoAntigen Information of KCNQ1-NCOR2 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of KCNQ1-NCOR2

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
5345LNRVEDKNLEKQMRKCNQ1NCOR2chr112799267chr121249113461902

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KCNQ1-NCOR2

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN5345LNRVEDKNLEKQMR-7.15543-7.26883
HLA-B14:023BVN5345LNRVEDKNLEKQMR-4.77435-5.80965
HLA-B52:013W395345LNRVEDKNLEKQMR-6.80875-6.92215
HLA-B52:013W395345LNRVEDKNLEKQMR-4.20386-5.23916
HLA-A11:014UQ25345LNRVEDKNLEKQMR-7.5194-8.5547
HLA-A11:014UQ25345LNRVEDKNLEKQMR-6.9601-7.0735
HLA-A24:025HGA5345LNRVEDKNLEKQMR-7.52403-7.63743
HLA-A24:025HGA5345LNRVEDKNLEKQMR-5.82433-6.85963
HLA-B27:056PYJ5345LNRVEDKNLEKQMR-3.28285-4.31815
HLA-B44:053DX85345LNRVEDKNLEKQMR-5.91172-6.94702
HLA-B44:053DX85345LNRVEDKNLEKQMR-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of KCNQ1-NCOR2

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
KCNQ1-NCOR2chr112799267chr12124911346817RVEDKNLEKCGAGTAGAAGACAAGAACCTGGAGAAG
KCNQ1-NCOR2chr112799267chr12124911346919VEDKNLEKQMGTAGAAGACAAGAACCTGGAGAAGCAGATG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of KCNQ1-NCOR2

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
STADKCNQ1-NCOR2chr112799267ENST00000155840chr12124911346ENST00000404621TCGA-HU-A4GH-01A

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Potential target of CAR-T therapy development for KCNQ1-NCOR2

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000155840+1516300_320598677.0IntramembranePore-forming%3B Name%3DSegment H5
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000335475+1516300_320471550.0IntramembranePore-forming%3B Name%3DSegment H5
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000155840+1516122_142598677.0TransmembraneHelical%3B Name%3DSegment S1
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000155840+1516148_168598677.0TransmembraneHelical%3B Name%3DSegment S2
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000155840+1516197_217598677.0TransmembraneHelical%3B Name%3DSegment S3
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000155840+1516226_248598677.0TransmembraneHelical%3B Voltage-sensor%3B Name%3DSegment S4
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000155840+1516262_282598677.0TransmembraneHelical%3B Name%3DSegment S5
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000155840+1516328_348598677.0TransmembraneHelical%3B Name%3DSegment S6
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000335475+1516122_142471550.0TransmembraneHelical%3B Name%3DSegment S1
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000335475+1516148_168471550.0TransmembraneHelical%3B Name%3DSegment S2
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000335475+1516197_217471550.0TransmembraneHelical%3B Name%3DSegment S3
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000335475+1516226_248471550.0TransmembraneHelical%3B Voltage-sensor%3B Name%3DSegment S4
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000335475+1516262_282471550.0TransmembraneHelical%3B Name%3DSegment S5
HgeneKCNQ1chr11:2799267chr12:124911346ENST00000335475+1516328_348471550.0TransmembraneHelical%3B Name%3DSegment S6

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to KCNQ1-NCOR2

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to KCNQ1-NCOR2

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

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