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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:KDM2B-LRRIQ1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KDM2B-LRRIQ1
FusionPDB ID: 41750
FusionGDB2.0 ID: 41750
HgeneTgene
Gene symbol

KDM2B

LRRIQ1

Gene ID

84678

84125

Gene namelysine demethylase 2Bleucine rich repeats and IQ motif containing 1
SynonymsCXXC2|FBXL10|Fbl10|JHDM1B|PCCX2-
Cytomap

12q24.31

12q21.31

Type of geneprotein-codingprotein-coding
Descriptionlysine-specific demethylase 2BCXXC-type zinc finger protein 2F-box and leucine-rich repeat protein 10F-box protein FBL10F-box/LRR-repeat protein 10JEMMA (Jumonji domain, EMSY-interactor, methyltransferase motif) protein[Histone-H3]-lysine-36 demethyleucine-rich repeat and IQ domain-containing protein 1testicular tissue protein Li 111
Modification date2020031320200320
UniProtAcc

Q8NHM5

Main function of 5'-partner protein: FUNCTION: Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36' (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (PubMed:16362057, PubMed:17994099). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:17994099, ECO:0000269|PubMed:26237645, ECO:0000305}.

Q96JM4

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000377069, ENST00000377071, 
ENST00000536437, ENST00000538046, 
ENST00000542973, ENST00000543852, 
ENST00000528777, ENST00000393217, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 11 X 9=12878 X 8 X 5=320
# samples 1510
** MAII scorelog2(15/1287*10)=-3.10097764772482
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/320*10)=-1.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KDM2B [Title/Abstract] AND LRRIQ1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KDM2B [Title/Abstract] AND LRRIQ1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KDM2B(122012452)-LRRIQ1(85638567), # samples:3
Anticipated loss of major functional domain due to fusion event.KDM2B-LRRIQ1 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.
KDM2B-LRRIQ1 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.
KDM2B-LRRIQ1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
KDM2B-LRRIQ1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
KDM2B-LRRIQ1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
KDM2B-LRRIQ1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor 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
HgeneKDM2B

GO:0035518

histone H2A monoubiquitination

16943429

HgeneKDM2B

GO:0070544

histone H3-K36 demethylation

26237645



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/chr12:122012452/chr12:85638567)
- 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 KDM2B (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 LRRIQ1 (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)
ENST00000377069KDM2Bchr12122012452-ENST00000393217LRRIQ1chr1285638567+1028711386835149
ENST00000377071KDM2Bchr12122012452-ENST00000393217LRRIQ1chr1285638567+78747073594173
ENST00000538046KDM2Bchr12122012452-ENST00000393217LRRIQ1chr1285638567+818501104625173

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
ENST00000377069ENST00000393217KDM2Bchr12122012452-LRRIQ1chr1285638567+0.0100806940.9899193
ENST00000377071ENST00000393217KDM2Bchr12122012452-LRRIQ1chr1285638567+0.0029963810.9970036
ENST00000538046ENST00000393217KDM2Bchr12122012452-LRRIQ1chr1285638567+0.0026965750.99730337

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 KDM2B-LRRIQ1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KDM2Bchr12122012452LRRIQ1chr1285638567470129KMPDPDFTVRDVKLLVGKTCKQRRHG
KDM2Bchr12122012452LRRIQ1chr1285638567501129KMPDPDFTVRDVKLLVGKTCKQRRHG
KDM2Bchr12122012452LRRIQ1chr1285638567711105KMPDPDFTVRDVKLLVGKTCKQRRHG

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Potential FusionNeoAntigen Information of KDM2B-LRRIQ1 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.
KDM2B-LRRIQ1_122012452_85638567.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)
KDM2B-LRRIQ1chr12122012452chr1285638567711HLA-B27:14VRDVKLLVGK0.99480.5745818
KDM2B-LRRIQ1chr12122012452chr1285638567711HLA-A30:01TVRDVKLLVGK0.99760.8025718

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Potential FusionNeoAntigen Information of KDM2B-LRRIQ1 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.
KDM2B-LRRIQ1_122012452_85638567.msa

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)
KDM2B-LRRIQ1chr12122012452chr1285638567711DRB1-0123VRDVKLLVGKTCKQR823
KDM2B-LRRIQ1chr12122012452chr1285638567711DRB1-0123TVRDVKLLVGKTCKQ722

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Fusion breakpoint peptide structures of KDM2B-LRRIQ1

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
2597FTVRDVKLLVGKTCKDM2BLRRIQ1chr12122012452chr1285638567711

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KDM2B-LRRIQ1

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-B14:023BVN2597FTVRDVKLLVGKTC-7.9962-8.1096
HLA-B14:023BVN2597FTVRDVKLLVGKTC-5.70842-6.74372
HLA-B52:013W392597FTVRDVKLLVGKTC-6.83737-6.95077
HLA-B52:013W392597FTVRDVKLLVGKTC-4.4836-5.5189
HLA-A11:014UQ22597FTVRDVKLLVGKTC-10.0067-10.1201
HLA-A11:014UQ22597FTVRDVKLLVGKTC-9.03915-10.0745
HLA-A24:025HGA2597FTVRDVKLLVGKTC-6.56204-6.67544
HLA-A24:025HGA2597FTVRDVKLLVGKTC-5.42271-6.45801
HLA-B44:053DX82597FTVRDVKLLVGKTC-7.85648-8.89178
HLA-B44:053DX82597FTVRDVKLLVGKTC-5.3978-5.5112
HLA-A02:016TDR2597FTVRDVKLLVGKTC-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of KDM2B-LRRIQ1

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
KDM2B-LRRIQ1chr12122012452chr1285638567718TVRDVKLLVGKACGTCAAACTCCTAGTGGGCAAGACTTGTAAGC
KDM2B-LRRIQ1chr12122012452chr1285638567818VRDVKLLVGKTCAAACTCCTAGTGGGCAAGACTTGTAAGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
KDM2B-LRRIQ1chr12122012452chr1285638567722TVRDVKLLVGKTCKQACGTCAAACTCCTAGTGGGCAAGACTTGTAAGCAGAGAAGACACG
KDM2B-LRRIQ1chr12122012452chr1285638567823VRDVKLLVGKTCKQRTCAAACTCCTAGTGGGCAAGACTTGTAAGCAGAGAAGACACGGAT

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Information of the samples that have these potential fusion neoantigens of KDM2B-LRRIQ1

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
SARCKDM2B-LRRIQ1chr12122012452ENST00000377069chr1285638567ENST00000393217TCGA-DX-A3LS-01A

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Potential target of CAR-T therapy development for KDM2B-LRRIQ1

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

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 KDM2B-LRRIQ1

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 KDM2B-LRRIQ1

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