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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:KDM5B-ITPKB

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KDM5B-ITPKB
FusionPDB ID: 41860
FusionGDB2.0 ID: 41860
HgeneTgene
Gene symbol

KDM5B

ITPKB

Gene ID

10765

3707

Gene namelysine demethylase 5Binositol-trisphosphate 3-kinase B
SynonymsCT31|JARID1B|MRT65|PLU-1|PLU1|PPP1R98|PUT1|RBBP2H1A|RBP2-H1IP3-3KB|IP3K|IP3K-B|IP3KB|PIG37
Cytomap

1q32.1

1q42.12

Type of geneprotein-codingprotein-coding
Descriptionlysine-specific demethylase 5Bcancer/testis antigen 31histone demethylase JARID1Bjumonji, AT rich interactive domain 1Bjumonji/ARID domain-containing protein 1Blysine (K)-specific demethylase 5Bprotein phosphatase 1, regulatory subunit 98putative Dinositol-trisphosphate 3-kinase BIP3 3-kinase BIP3K Binositol 1,4,5-trisphosphate 3-kinase BinsP 3-kinase Bproliferation-inducing protein 37
Modification date2020032020200313
UniProtAcc

Q9UGL1

Main function of 5'-partner protein: FUNCTION: Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code (PubMed:24952722, PubMed:27214403, PubMed:28262558). Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Favors the proliferation of breast cancer cells by repressing tumor suppressor genes such as BRCA1 and HOXA5 (PubMed:24952722). In contrast, may act as a tumor suppressor for melanoma. Represses the CLOCK-ARNTL/BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2 (By similarity). {ECO:0000250|UniProtKB:Q80Y84, ECO:0000269|PubMed:12657635, ECO:0000269|PubMed:16645588, ECO:0000269|PubMed:17320161, ECO:0000269|PubMed:17363312, ECO:0000269|PubMed:24952722, ECO:0000269|PubMed:26645689, ECO:0000269|PubMed:26741168, ECO:0000269|PubMed:27214403, ECO:0000269|PubMed:28262558}.

P27987

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000367264, ENST00000367265, 
ENST00000456180, 
ENST00000366784, 
ENST00000272117, ENST00000429204, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 13 X 9=163812 X 10 X 3=360
# samples 1713
** MAII scorelog2(17/1638*10)=-3.26832870550331
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/360*10)=-1.46948528330122
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KDM5B [Title/Abstract] AND ITPKB [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KDM5B [Title/Abstract] AND ITPKB [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KDM5B(202742246)-ITPKB(226836472), # samples:3
Anticipated loss of major functional domain due to fusion event.KDM5B-ITPKB 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.
KDM5B-ITPKB 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.
KDM5B-ITPKB 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.
KDM5B-ITPKB 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
HgeneKDM5B

GO:0034720

histone H3-K4 demethylation

20228790

TgeneITPKB

GO:0032957

inositol trisphosphate metabolic process

1654894

TgeneITPKB

GO:0071277

cellular response to calcium ion

1654894



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/chr1:202742246/chr1:226836472)
- 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 KDM5B (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 ITPKB (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)
ENST00000367265KDM5Bchr1202742246-ENST00000272117ITPKBchr1226836472-563117419342649571
ENST00000367265KDM5Bchr1202742246-ENST00000429204ITPKBchr1226836472-563117419342649571
ENST00000367264KDM5Bchr1202742246-ENST00000272117ITPKBchr1226836472-45796891131597494
ENST00000367264KDM5Bchr1202742246-ENST00000429204ITPKBchr1226836472-45796891131597494

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
ENST00000367265ENST00000272117KDM5Bchr1202742246-ITPKBchr1226836472-0.0047552610.9952447
ENST00000367265ENST00000429204KDM5Bchr1202742246-ITPKBchr1226836472-0.0047552610.9952447
ENST00000367264ENST00000272117KDM5Bchr1202742246-ITPKBchr1226836472-0.0022426550.9977574
ENST00000367264ENST00000429204KDM5Bchr1202742246-ITPKBchr1226836472-0.0022426550.9977574

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 KDM5B-ITPKB

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KDM5Bchr1202742246ITPKBchr12268364721741269NPYNLFLSGDSLRSKSWRKIKNMVHW
KDM5Bchr1202742246ITPKBchr1226836472689192NPYNLFLSGDSLRSKSWRKIKNMVHW

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Potential FusionNeoAntigen Information of KDM5B-ITPKB 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.
KDM5B-ITPKB_202742246_226836472.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)
KDM5B-ITPKBchr1202742246chr1226836472689HLA-A30:08RSKSWRKIK0.99670.72451221
KDM5B-ITPKBchr1202742246chr1226836472689HLA-A30:08SLRSKSWRK0.99540.64411019
KDM5B-ITPKBchr1202742246chr1226836472689HLA-B57:01LSGDSLRSKSW10.9525617
KDM5B-ITPKBchr1202742246chr1226836472689HLA-B58:02LSGDSLRSKSW0.99990.9018617
KDM5B-ITPKBchr1202742246chr1226836472689HLA-B57:03LSGDSLRSKSW0.99980.9461617
KDM5B-ITPKBchr1202742246chr1226836472689HLA-B58:01LSGDSLRSKSW0.99960.9029617
KDM5B-ITPKBchr1202742246chr1226836472689HLA-A30:01RSKSWRKIK0.99690.86851221
KDM5B-ITPKBchr1202742246chr1226836472689HLA-A30:01SLRSKSWRK0.99530.76611019
KDM5B-ITPKBchr1202742246chr1226836472689HLA-C06:08LRSKSWRKI0.71550.98361120
KDM5B-ITPKBchr1202742246chr1226836472689HLA-C06:17LRSKSWRKI0.00540.9921120
KDM5B-ITPKBchr1202742246chr1226836472689HLA-C06:02LRSKSWRKI0.00540.9921120
KDM5B-ITPKBchr1202742246chr1226836472689HLA-B57:10LSGDSLRSKSW10.9525617
KDM5B-ITPKBchr1202742246chr1226836472689HLA-B57:04LSGDSLRSKSW0.99990.8277617
KDM5B-ITPKBchr1202742246chr1226836472689HLA-B58:06LSGDSLRSKSW0.99960.8442617
KDM5B-ITPKBchr1202742246chr1226836472689HLA-B57:02LSGDSLRSKSW0.99960.9415617

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Potential FusionNeoAntigen Information of KDM5B-ITPKB 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 KDM5B-ITPKB

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
5623LSGDSLRSKSWRKIKDM5BITPKBchr1202742246chr1226836472689

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KDM5B-ITPKB

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-B14:023BVN5623LSGDSLRSKSWRKI-8.60826-8.72166
HLA-B14:023BVN5623LSGDSLRSKSWRKI-2.66483-3.70013
HLA-B52:013W395623LSGDSLRSKSWRKI-6.90747-7.02087
HLA-B52:013W395623LSGDSLRSKSWRKI-1.88432-2.91962
HLA-A11:014UQ25623LSGDSLRSKSWRKI-11.2418-11.3552
HLA-A24:025HGA5623LSGDSLRSKSWRKI-9.24546-9.35886
HLA-A24:025HGA5623LSGDSLRSKSWRKI-4.08507-5.12037
HLA-B44:053DX85623LSGDSLRSKSWRKI-7.05529-7.16869
HLA-B44:053DX85623LSGDSLRSKSWRKI-4.33606-5.37136
HLA-A02:016TDR5623LSGDSLRSKSWRKI-6.57504-6.68844

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Vaccine Design for the FusionNeoAntigens of KDM5B-ITPKB

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
KDM5B-ITPKBchr1202742246chr12268364721019SLRSKSWRKAGCCTAAGGAGCAAATCATGGAGGAAG
KDM5B-ITPKBchr1202742246chr12268364721120LRSKSWRKICTAAGGAGCAAATCATGGAGGAAGATA
KDM5B-ITPKBchr1202742246chr12268364721221RSKSWRKIKAGGAGCAAATCATGGAGGAAGATAAAA
KDM5B-ITPKBchr1202742246chr1226836472617LSGDSLRSKSWCTGTCCGGAGACAGCCTAAGGAGCAAATCATGG

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 KDM5B-ITPKB

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
PCPGKDM5B-ITPKBchr1202742246ENST00000367264chr1226836472ENST00000272117TCGA-WB-A81J-01A

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Potential target of CAR-T therapy development for KDM5B-ITPKB

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 KDM5B-ITPKB

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 KDM5B-ITPKB

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