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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:DNAJB12-NEK5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DNAJB12-NEK5
FusionPDB ID: 23407
FusionGDB2.0 ID: 23407
HgeneTgene
Gene symbol

DNAJB12

NEK5

Gene ID

54788

341676

Gene nameDnaJ heat shock protein family (Hsp40) member B12NIMA related kinase 5
SynonymsDJ10-
Cytomap

10q22.1

13q14.3

Type of geneprotein-codingprotein-coding
DescriptiondnaJ homolog subfamily B member 12DnaJ (Hsp40) homolog, subfamily B, member 12serine/threonine-protein kinase Nek5NIMA (never in mitosis gene a)-related kinase 5nimA-related protein kinase 5
Modification date2020031320200313
UniProtAcc

Q9NXW2

Main function of 5'-partner protein: FUNCTION: Acts as a co-chaperone with HSPA8/Hsc70; required to promote protein folding and trafficking, prevent aggregation of client proteins, and promote unfolded proteins to endoplasmic reticulum-associated degradation (ERAD) pathway (PubMed:21150129, PubMed:21148293). Acts by determining HSPA8/Hsc70's ATPase and polypeptide-binding activities. Can also act independently of HSPA8/Hsc70: together with DNAJB14, acts as a chaperone that promotes maturation of potassium channels KCND2 and KCNH2 by stabilizing nascent channel subunits and assembling them into tetramers (PubMed:27916661). While stabilization of nascent channel proteins is dependent on HSPA8/Hsc70, the process of oligomerization of channel subunits is independent of HSPA8/Hsc70 (PubMed:27916661). When overexpressed, forms membranous structures together with DNAJB14 and HSPA8/Hsc70 within the nucleus; the role of these structures, named DJANGOs, is still unclear (PubMed:24732912). {ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27916661}.; FUNCTION: (Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection (PubMed:21673190, PubMed:24675744). {ECO:0000269|PubMed:21673190, ECO:0000269|PubMed:24675744}.

Q6P3R8

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000338820, ENST00000394903, 
ENST00000444643, ENST00000461919, 
ENST00000529080, ENST00000355568, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 2 X 2=123 X 3 X 3=27
# samples 43
** MAII scorelog2(4/12*10)=1.73696559416621
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: DNAJB12 [Title/Abstract] AND NEK5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DNAJB12 [Title/Abstract] AND NEK5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DNAJB12(74114523)-NEK5(52650279), # samples:1
Anticipated loss of major functional domain due to fusion event.DNAJB12-NEK5 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.
DNAJB12-NEK5 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
HgeneDNAJB12

GO:0034622

cellular protein-containing complex assembly

27916661

HgeneDNAJB12

GO:0036503

ERAD pathway

21148293|21150129

HgeneDNAJB12

GO:0051085

chaperone cofactor-dependent protein refolding

27916661

HgeneDNAJB12

GO:0071218

cellular response to misfolded protein

21148293|21150129



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/chr10:74114523/chr13:52650279)
- 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 DNAJB12 (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 NEK5 (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)
ENST00000394903DNAJB12chr1074114523-ENST00000355568NEK5chr1352650279-1516385241864207
ENST00000338820DNAJB12chr1074114523-ENST00000355568NEK5chr1352650279-1516385241864207
ENST00000444643DNAJB12chr1074114523-ENST00000355568NEK5chr1352650279-1597466322945207

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
ENST00000394903ENST00000355568DNAJB12chr1074114523-NEK5chr1352650279-0.0014761820.9985239
ENST00000338820ENST00000355568DNAJB12chr1074114523-NEK5chr1352650279-0.0014761820.9985239
ENST00000444643ENST00000355568DNAJB12chr1074114523-NEK5chr1352650279-0.001269430.9987306

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 DNAJB12-NEK5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DNAJB12chr1074114523NEK5chr135265027938546SWRRHSGCIRRREFADIEKDLKQMRL
DNAJB12chr1074114523NEK5chr135265027946646SWRRHSGCIRRREFADIEKDLKQMRL

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Potential FusionNeoAntigen Information of DNAJB12-NEK5 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.
DNAJB12-NEK5_74114523_52650279.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)
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B27:05RRREFADIEK0.9990.8222919
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B13:01REFADIEKDL0.97950.95551121
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B47:01REFADIEKDL0.97740.55831121
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B39:13REFADIEKDL0.85510.90091121
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B27:14RREFADIEK0.95030.80871019
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B27:14RRREFADIEK0.99870.7608919
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B40:06REFADIEKDL0.99670.68841121
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B27:03RRREFADIEK0.98420.8325919
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B39:08REFADIEKDL0.9470.85881121
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B27:10RRREFADIEK0.99840.9063919
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B40:04REFADIEKDL0.99230.76051121
DNAJB12-NEK5chr1074114523chr1352650279385HLA-B41:03REFADIEKDL0.79210.55681121

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Potential FusionNeoAntigen Information of DNAJB12-NEK5 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.
DNAJB12-NEK5_74114523_52650279.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)
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0301REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0303REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0307REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0313REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0315REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0318REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0320REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0322REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0328REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0330REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0332REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0334REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0336REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0344REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0346REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0348REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0350REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0352REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-0354REFADIEKDLKQMRL1126
DNAJB12-NEK5chr1074114523chr1352650279385DRB1-1107REFADIEKDLKQMRL1126

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Fusion breakpoint peptide structures of DNAJB12-NEK5

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
2690GCIRRREFADIEKDDNAJB12NEK5chr1074114523chr1352650279385

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DNAJB12-NEK5

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-B14:023BVN2690GCIRRREFADIEKD-7.9962-8.1096
HLA-B14:023BVN2690GCIRRREFADIEKD-5.70842-6.74372
HLA-B52:013W392690GCIRRREFADIEKD-6.83737-6.95077
HLA-B52:013W392690GCIRRREFADIEKD-4.4836-5.5189
HLA-A11:014UQ22690GCIRRREFADIEKD-10.0067-10.1201
HLA-A11:014UQ22690GCIRRREFADIEKD-9.03915-10.0745
HLA-A24:025HGA2690GCIRRREFADIEKD-6.56204-6.67544
HLA-A24:025HGA2690GCIRRREFADIEKD-5.42271-6.45801
HLA-B44:053DX82690GCIRRREFADIEKD-7.85648-8.89178
HLA-B44:053DX82690GCIRRREFADIEKD-5.3978-5.5112
HLA-A02:016TDR2690GCIRRREFADIEKD-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of DNAJB12-NEK5

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
DNAJB12-NEK5chr1074114523chr13526502791019RREFADIEKGAGTTCGCGGACATTGAAAAAGACTTG
DNAJB12-NEK5chr1074114523chr13526502791121REFADIEKDLTTCGCGGACATTGAAAAAGACTTGAAACAA
DNAJB12-NEK5chr1074114523chr1352650279919RRREFADIEKCGCGAGTTCGCGGACATTGAAAAAGACTTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
DNAJB12-NEK5chr1074114523chr13526502791126REFADIEKDLKQMRLTTCGCGGACATTGAAAAAGACTTGAAACAAATGAGGCTTCAGAAC

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Information of the samples that have these potential fusion neoantigens of DNAJB12-NEK5

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
STADDNAJB12-NEK5chr1074114523ENST00000338820chr1352650279ENST00000355568TCGA-BR-8284-01A

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Potential target of CAR-T therapy development for DNAJB12-NEK5

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 DNAJB12-NEK5

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 DNAJB12-NEK5

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