Fusion Gene Studies
in Kim Lab

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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:KHDC1-NLK (FusionGDB2 ID:HG80759TG51701)

Fusion Gene Summary for KHDC1-NLK

check button Fusion gene summary
Fusion gene informationFusion gene name: KHDC1-NLK
Fusion gene ID: hg80759tg51701
HgeneTgene
Gene symbol

KHDC1

NLK

Gene ID

80759

51701

Gene nameKH domain containing 1nemo like kinase
SynonymsC6orf147|C6orf148|Em:AC019205.8|KHDC1L|NDG1|bA257K9.4-
Cytomap('KHDC1')('NLK')

6q13

17q11.2

Type of geneprotein-codingprotein-coding
DescriptionKH homology domain-containing protein 1KH homology domain containing 1Putative KHDC1-like proteinserine/threonine-protein kinase NLK
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST00000370384, ENST00000484801, 
ENST00000257765, 
Fusion gene scores* DoF score6 X 3 X 4=7210 X 10 X 5=500
# samples 615
** MAII scorelog2(6/72*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/500*10)=-1.73696559416621
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: KHDC1 [Title/Abstract] AND NLK [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointKHDC1(74001721)-NLK(26449629), # samples:2
Anticipated loss of major functional domain due to fusion event.KHDC1-NLK 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.
KHDC1-NLK 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.
KHDC1-NLK 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.
KHDC1-NLK 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.
* 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
TgeneNLK

GO:0050821

protein stabilization

25512613


check buttonFusion gene breakpoints across KHDC1 (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 NLK (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
* 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
ChimerDB4BRCATCGA-A1-A0SO-01AKHDC1chr6

74001721

-NLKchr17

26449629

+


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Fusion Gene ORF analysis for KHDC1-NLK

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-intronENST00000370384ENST00000582037KHDC1chr6

74001721

-NLKchr17

26449629

+
5CDS-intronENST00000370384ENST00000583517KHDC1chr6

74001721

-NLKchr17

26449629

+
5UTR-3CDSENST00000484801ENST00000407008KHDC1chr6

74001721

-NLKchr17

26449629

+
5UTR-intronENST00000484801ENST00000582037KHDC1chr6

74001721

-NLKchr17

26449629

+
5UTR-intronENST00000484801ENST00000583517KHDC1chr6

74001721

-NLKchr17

26449629

+
In-frameENST00000370384ENST00000407008KHDC1chr6

74001721

-NLKchr17

26449629

+
intron-3CDSENST00000257765ENST00000407008KHDC1chr6

74001721

-NLKchr17

26449629

+
intron-intronENST00000257765ENST00000582037KHDC1chr6

74001721

-NLKchr17

26449629

+
intron-intronENST00000257765ENST00000583517KHDC1chr6

74001721

-NLKchr17

26449629

+

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)
ENST00000370384KHDC1chr674001721-ENST00000407008NLKchr1726449629+35787075011832443

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
ENST00000370384ENST00000407008KHDC1chr674001721-NLKchr1726449629+0.0004300940.99956995

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Fusion Genomic Features for KHDC1-NLK


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)
KHDC1chr674001720-NLKchr1726449628+2.60E-111
KHDC1chr674001720-NLKchr1726449628+2.60E-111

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 KHDC1-NLK


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/chr6:74001721/chr17:26449629)
- 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
..
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 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
HgeneKHDC1chr6:74001721chr17:26449629ENST00000370384-2533_5068238.0TransmembraneHelical
HgeneKHDC1chr6:74001721chr17:26449629ENST00000370384-257_2968238.0TransmembraneHelical
TgeneNLKchr6:74001721chr17:26449629ENST00000407008011298_300152528.0MotifNote=TQE
TgeneNLKchr6:74001721chr17:26449629ENST00000407008011428_527152528.0RegionRequired for homodimerization and kinase activation and localization to the nucleus

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneKHDC1chr6:74001721chr17:26449629ENST00000257765-1496_1550165.0DomainNote=KH%3B atypical
HgeneKHDC1chr6:74001721chr17:26449629ENST00000370384-2596_15568238.0DomainNote=KH%3B atypical
HgeneKHDC1chr6:74001721chr17:26449629ENST00000257765-1433_500165.0TransmembraneHelical
HgeneKHDC1chr6:74001721chr17:26449629ENST00000257765-147_290165.0TransmembraneHelical
TgeneNLKchr6:74001721chr17:26449629ENST00000407008011106_111152528.0Compositional biasNote=Poly-Ala
TgeneNLKchr6:74001721chr17:26449629ENST00000407008011115_119152528.0Compositional biasNote=Poly-Ala
TgeneNLKchr6:74001721chr17:26449629ENST0000040700801122_25152528.0Compositional biasNote=Poly-Ala
TgeneNLKchr6:74001721chr17:26449629ENST0000040700801127_34152528.0Compositional biasNote=Poly-His
TgeneNLKchr6:74001721chr17:26449629ENST0000040700801142_48152528.0Compositional biasNote=Poly-His
TgeneNLKchr6:74001721chr17:26449629ENST0000040700801171_83152528.0Compositional biasNote=Poly-Ala
TgeneNLKchr6:74001721chr17:26449629ENST00000407008011138_427152528.0DomainProtein kinase
TgeneNLKchr6:74001721chr17:26449629ENST00000407008011144_152152528.0Nucleotide bindingATP


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Fusion Gene Sequence for KHDC1-NLK


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.
>41944_41944_1_KHDC1-NLK_KHDC1_chr6_74001721_ENST00000370384_NLK_chr17_26449629_ENST00000407008_length(transcript)=3578nt_BP=707nt
GGCGGAAGAGGCGGGTCCAGGGCGGTGTAATTAAGGCGCGGAGCCCAGACCCTCCTGCTACAGTGCCTCGGGCTTTCCTGGAGGCGGGCG
GCGGGATGCTGCTCCGTTCTCCGGGTCCTCTCCTCCGGTTCTTGTCGTTTGGTCACGCCCTCAGTTCAGTCGGTTATTGGAAAACGATCA
AGGCCCAAAGATGGTTTACGTGGCGTTGTGGATGTTATCACCGTTGTTTGGTGACCGAGCCTGGAGCTTGAGCCCTGGGACGTCTTGCCA
GCCGCATGTGGTCCCGTGCCCACTTCTCGCGGTGGCGCGTTAATCCACCTAGACTGTGCATTGGTCCAGTCTGGGTTGACCCCGACCCGA
AGTGGCCCTTTCCTTCGCGTCCTGAACTTCGCTTCTCCGTCGGTGTCTGGTCTCTTCCCGCCGGCGGGCTCTGCGGTGGCGGGAGGAGCT
GTACTACTCGTGCCTTAGCGCACCCTTACTTTCCCAGGCCAGAAACGCGAAATGCTGTCGGCCTTCCAGAGGCTGTTCCGAGTCTTATTT
GTGATTGAAACAGTCTCAGAATACGGAGTCCTGATCTTCATTTATGGATGGCCCTTTCTCCAGACCCTTGCGATGCTCCTGATCGGGACA
GTGTCTTTCCACCTTTGGATCCGCAGAAATCGAGAGAGAAACTCAAGGAGCGGAAAGACTAGATGCCGATCCAAAAGGTCAGTAACAGAT
CCAAGAGATGGAAAGAGAGTAGCGCTCAAAAAGATGCCCAACGTCTTCCAGAATCTGGTCTCTTGCAAAAGGGTCTTCCGGGAATTGAAG
ATGTTGTGTTTTTTTAAGCATGATAATGTACTCTCTGCCCTTGACATACTCCAACCTCCACACATTGACTATTTTGAAGAAATATATGTT
GTCACAGAATTGATGCAGAGTGACCTACATAAAATTATCGTCTCTCCTCAACCACTCAGCTCAGATCATGTCAAAGTTTTTCTTTATCAG
ATTTTGCGAGGTTTGAAATATCTCCATTCAGCTGGCATTTTACATCGAGACATTAAGCCAGGGAATCTCCTTGTGAACAGCAACTGTGTT
CTAAAGATTTGTGATTTTGGATTGGCCAGAGTGGAAGAATTAGATGAATCCCGTCATATGACTCAGGAAGTTGTTACTCAGTATTATCGG
GCTCCAGAAATCCTGATGGGCAGCCGTCATTACAGCAATGCTATTGACATCTGGTCTGTGGGATGTATCTTTGCAGAACTACTAGGACGA
AGAATATTGTTTCAGGCACAGAGTCCCATTCAGCAGTTGGATTTGATCACGGATCTGTTGGGCACACCATCACTGGAAGCAATGAGGACA
GCTTGTGAAGGCGCTAAGGCACATATACTCAGGGGTCCTCATAAACAGCCATCTCTTCCTGTACTCTATACCCTGTCTAGCCAGGCTACA
CATGAAGCTGTTCATCTCCTTTGCAGGATGTTGGTCTTTGATCCATCCAAAAGAATATCCGCTAAGGATGCCTTAGCCCACCCCTACCTA
GATGAAGGGCGACTACGATATCACACATGTATGTGTAAATGTTGCTTTTCCACCTCCACTGGAAGAGTTTATACCAGTGACTTTGAGCCT
GTCACCAATCCCAAATTTGATGACACTTTCGAGAAGAACCTCAGTTCTGTCCGACAGGTTAAAGAAATTATTCATCAGTTCATTTTGGAA
CAGCAGAAAGGAAACAGAGTGCCTCTCTGCATCAACCCTCAGTCTGCTGCTTTTAAGAGCTTTATTAGTTCCACTGTTGCTCAGCCATCT
GAGATGCCCCCATCTCCTCTGGTGTGGGAGTGATGGTGGAAGATAATGTACTACTGAAGATGTAATGTAGCTTTCCACTGGAGTCTGGGA
TTTGCAATTCTGGAGGTTAATCATGCTTGTACTGTAATTTTACTAATGAAGTTTTAAATTAACAACCACTACTTGTATGATATGAATAAT
ATTTAGAAATGTTACTAGACTTTTAATCTTGTAAAGTGGTTGTGCTTTTAGAAGAAAAATATTTTACCCAGAGTTGCACATGTTTTATGA
ATTTAGTGCAGCTGTTATGGCTCACCTCAGAACAAAAGAGAATTGAACCAAATTTGGGAGTTTGGGGTTTTATGTTTTGTTTTTCTTTTC
TAAAATGAAGTGAGATTGTTCACACACACACACACACACACACACACACACAAACACAAAGGACAGTCATACATTTTGATATTTGAGCCA
TTCCTAAAGATTTGGGGTTTTCTAAAACTAAAGAATCTAGGAACCTTGCCTGCGACCAATCATGGAGCCACGTGAGCTGATCGTGGCTGC
ACCTGGGGGGAGGGTAGGGAGGAGGGGCATGCCACCTAATGATCAAGCCCTATAATTAGCTTCTCATTAGAGCCGTGATGGTGATGTGTG
CTGTCTAAAATCCAATGTTGTGGGTAGAGAGAATGAGTTTGTGACTAGGAGAGACTAAACTTTTGTTTTCCTTACCCAGTATAAATATAT
ATATATATATTTAATCTATTTTTATTAGAAGTTTTTCTGCTCTTTCTTACATAAAAGAACCCCAAGCATGCATCTTTCATGTGTGTAAAT
AATTCATTTCTGGGCTAATTTCAAAAGAATCCCAATATTGCTGTATAGAAAGAGAACTAGCTTGCACATTTTAGGTCTGTGAAATTTTGT
GAGACTTTTCCTGCACTGGACAGTAAAAAAATAATAAAAGACAAAAACAAATTTAAAAAAAAATTTAAGCCACAAAAAAAGGCACATAGG
GAATTATGTCAAATGTGTTTGTGTCCTTAGGCAAAGCTGTGGGAGTCTTGAAATGTCACAGTAGTAAATAACTTATTACTTTTTGACAAG
TTCTTTTTTTCTGTTGGAACACTGAATTCTTCTGTGCATATGTACATATGAATACAAATCGAAGGCCTCTACCTCCTGGAGTTATACAAC
TTGGCTTGTTTACCTCCACATGCTGATGATGACTATTTTTTTTTTTTGAGTTCAGTGTGGAGACTTGAAACTTGAATGTCCCTTCCAACT
TTTATATTAAAAATAAAAAGACAAGAAAATTGAAGATCATTTTTCACCTGTACAAGGAATACTAATGGATCGTCTTAAAATTGGTCTAGG
AAAAAACCTTGGTGTGTGTTATGGACAATTAACTGTTAAAGTTATTGTAAGTTATCTGTATTTAGCAGAGTATTTTCAACTTGAGTGATC
TGAGCTGAATTTGAAGACTATTAATAAGTTATGTTTGGAAGTTTTAACTTCAATGAAGTAATTATTTGCTGTGAAAGAAACAAACATTGA
ATTACTAAACAAAGATGGTGCAATATCTTTGTTTTTTTTTTATGAGGCTCCTGAGAATCAACCCAACTGAAGCATTTCAATTCACTTGAA
TGAGAAACGTGTTTAGTATCAAAAGAGCCCAAGAAGACACTGGTGTGAAAGGTACAATCTCAGAGGTTGGTCAATTACCGTGGCACACTT

>41944_41944_1_KHDC1-NLK_KHDC1_chr6_74001721_ENST00000370384_NLK_chr17_26449629_ENST00000407008_length(amino acids)=443AA_BP=68
MLSAFQRLFRVLFVIETVSEYGVLIFIYGWPFLQTLAMLLIGTVSFHLWIRRNRERNSRSGKTRCRSKRSVTDPRDGKRVALKKMPNVFQ
NLVSCKRVFRELKMLCFFKHDNVLSALDILQPPHIDYFEEIYVVTELMQSDLHKIIVSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRD
IKPGNLLVNSNCVLKICDFGLARVEELDESRHMTQEVVTQYYRAPEILMGSRHYSNAIDIWSVGCIFAELLGRRILFQAQSPIQQLDLIT
DLLGTPSLEAMRTACEGAKAHILRGPHKQPSLPVLYTLSSQATHEAVHLLCRMLVFDPSKRISAKDALAHPYLDEGRLRYHTCMCKCCFS

--------------------------------------------------------------

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Fusion Gene PPI Analysis for KHDC1-NLK


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 KHDC1-NLK


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 KHDC1-NLK


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