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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:DNAJC3-FOXN3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DNAJC3-FOXN3
FusionPDB ID: 23540
FusionGDB2.0 ID: 23540
HgeneTgene
Gene symbol

DNAJC3

FOXN3

Gene ID

5611

1112

Gene nameDnaJ heat shock protein family (Hsp40) member C3forkhead box N3
SynonymsACPHD|ERdj6|HP58|P58|P58IPK|PRKRI|p58(IPK)C14orf116|CHES1|PRO1635
Cytomap

13q32.1

14q31.3-q32.11

Type of geneprotein-codingprotein-coding
DescriptiondnaJ homolog subfamily C member 3DnaJ (Hsp40) homolog, subfamily C, member 3ER-resident protein ERdj6endoplasmic reticulum DNA J domain-containing protein 6interferon-induced, double-stranded RNA-activated protein kinase inhibitorprotein kinase inhibforkhead box protein N3checkpoint suppressor 1
Modification date2020032920200313
UniProtAcc

Q13217

Main function of 5'-partner protein: FUNCTION: Involved in the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Acts as a negative regulator of the EIF2AK4/GCN2 kinase activity by preventing the phosphorylation of eIF-2-alpha at 'Ser-52' and hence attenuating general protein synthesis under ER stress, hypothermic and amino acid starving stress conditions (By similarity). Co-chaperone of HSPA8/HSC70, it stimulates its ATPase activity. May inhibit both the autophosphorylation of EIF2AK2/PKR and the ability of EIF2AK2 to catalyze phosphorylation of the EIF2A. May inhibit EIF2AK3/PERK activity. {ECO:0000250|UniProtKB:Q27968, ECO:0000250|UniProtKB:Q91YW3, ECO:0000269|PubMed:12601012, ECO:0000269|PubMed:8576172, ECO:0000269|PubMed:9447982, ECO:0000269|PubMed:9920933}.

O00409

Main function of 5'-partner protein: FUNCTION: Acts as a transcriptional repressor. May be involved in DNA damage-inducible cell cycle arrests (checkpoints). {ECO:0000269|PubMed:16102918}.
Ensembl transtripts involved in fusion geneENST idsENST00000376795, ENST00000602402, 
ENST00000555658, ENST00000261302, 
ENST00000345097, ENST00000555353, 
ENST00000557258, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 14 X 8=168019 X 14 X 9=2394
# samples 1820
** MAII scorelog2(18/1680*10)=-3.22239242133645
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(20/2394*10)=-3.58135124716878
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DNAJC3 [Title/Abstract] AND FOXN3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DNAJC3 [Title/Abstract] AND FOXN3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DNAJC3(96377506)-FOXN3(89817152), # samples:2
Anticipated loss of major functional domain due to fusion event.DNAJC3-FOXN3 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.
DNAJC3-FOXN3 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
TgeneFOXN3

GO:0045892

negative regulation of transcription, DNA-templated

16102918



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/chr13:96377506/chr14:89817152)
- 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 DNAJC3 (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 FOXN3 (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)
ENST00000602402DNAJC3chr1396377506+ENST00000345097FOXN3chr1489817152-7682510451439464
ENST00000602402DNAJC3chr1396377506+ENST00000261302FOXN3chr1489817152-7669510451439464
ENST00000602402DNAJC3chr1396377506+ENST00000557258FOXN3chr1489817152-2403510451373442
ENST00000602402DNAJC3chr1396377506+ENST00000555353FOXN3chr1489817152-1426510451373442
ENST00000376795DNAJC3chr1396377506+ENST00000345097FOXN3chr1489817152-7663491261420464
ENST00000376795DNAJC3chr1396377506+ENST00000261302FOXN3chr1489817152-7650491261420464
ENST00000376795DNAJC3chr1396377506+ENST00000557258FOXN3chr1489817152-2384491261354442
ENST00000376795DNAJC3chr1396377506+ENST00000555353FOXN3chr1489817152-1407491261354442

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
ENST00000602402ENST00000345097DNAJC3chr1396377506+FOXN3chr1489817152-0.0004025830.9995975
ENST00000602402ENST00000261302DNAJC3chr1396377506+FOXN3chr1489817152-0.0004023390.9995977
ENST00000602402ENST00000557258DNAJC3chr1396377506+FOXN3chr1489817152-0.0026961310.99730384
ENST00000602402ENST00000555353DNAJC3chr1396377506+FOXN3chr1489817152-0.0125337630.9874663
ENST00000376795ENST00000345097DNAJC3chr1396377506+FOXN3chr1489817152-0.0003944010.9996056
ENST00000376795ENST00000261302DNAJC3chr1396377506+FOXN3chr1489817152-0.0003941530.99960583
ENST00000376795ENST00000557258DNAJC3chr1396377506+FOXN3chr1489817152-0.0025245850.99747545
ENST00000376795ENST00000555353DNAJC3chr1396377506+FOXN3chr1489817152-0.0112661380.9887339

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 DNAJC3-FOXN3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DNAJC3chr1396377506FOXN3chr1489817152491155GKLDEAEDDFKKVSIGKGSLWCIDPE
DNAJC3chr1396377506FOXN3chr1489817152510155GKLDEAEDDFKKVSIGKGSLWCIDPE

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Potential FusionNeoAntigen Information of DNAJC3-FOXN3 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.
DNAJC3-FOXN3_96377506_89817152.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)
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:01VSIGKGSLW0.99970.9871221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B58:02VSIGKGSLW0.99940.97021221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B58:01VSIGKGSLW0.99930.9781221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B15:17VSIGKGSLW0.99860.93891221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:03VSIGKGSLW0.99760.99291221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B15:16VSIGKGSLW0.9960.8441221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B45:01AEDDFKKVS0.99320.7834514
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B50:02AEDDFKKVS0.9820.5772514
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-A32:13VSIGKGSLW0.89730.97991221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B41:01AEDDFKKVS0.27490.8433514
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B50:01AEDDFKKVS0.09240.6299514
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:01KVSIGKGSLW0.99990.98351121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B58:02KVSIGKGSLW0.99960.95891121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B58:01KVSIGKGSLW0.99920.9721121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:03KVSIGKGSLW0.99860.99041121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B15:17KVSIGKGSLW0.99720.9131121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B50:02AEDDFKKVSI0.99140.6133515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B44:03AEDDFKKVSI0.99130.9625515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B15:16KVSIGKGSLW0.98850.81921121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-A32:13KVSIGKGSLW0.96610.97371121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B45:01AEDDFKKVSI0.9570.7575515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B41:01AEDDFKKVSI0.88010.8417515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B39:13AEDDFKKVSI0.82580.8974515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:01KKVSIGKGSLW0.99990.98351021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B58:02KKVSIGKGSLW0.99920.95121021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B58:01KKVSIGKGSLW0.9990.97051021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:03KKVSIGKGSLW0.9990.98971021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B15:16KKVSIGKGSLW0.99560.82071021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B15:17KKVSIGKGSLW0.99050.91721021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B40:06AEDDFKKVS0.99310.5578514
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B39:08AEDDFKKVSI0.97080.8398515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:10VSIGKGSLW0.99970.9871221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:04VSIGKGSLW0.99960.77751221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B58:06VSIGKGSLW0.99920.94521221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:02VSIGKGSLW0.99840.97531221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B15:13VSIGKGSLW0.99510.80391221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-A32:01VSIGKGSLW0.98750.94781221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B15:24VSIGKGSLW0.94110.97031221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-A25:01VSIGKGSLW0.32980.87371221
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B50:05AEDDFKKVS0.09240.6299514
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B50:04AEDDFKKVS0.09240.6299514
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:10KVSIGKGSLW0.99990.98351121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:04KVSIGKGSLW0.99970.78111121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B58:06KVSIGKGSLW0.99960.90551121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B40:04AEDDFKKVSI0.99650.7421515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:02KVSIGKGSLW0.99620.97271121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B15:24KVSIGKGSLW0.99550.96381121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-A32:01KVSIGKGSLW0.99350.95861121
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B44:13AEDDFKKVSI0.99130.9625515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B44:26AEDDFKKVSI0.99130.9625515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B44:07AEDDFKKVSI0.99130.9625515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B41:03AEDDFKKVSI0.89740.5409515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B39:02AEDDFKKVSI0.85080.9011515
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:10KKVSIGKGSLW0.99990.98351021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:04KKVSIGKGSLW0.99950.77531021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B58:06KKVSIGKGSLW0.99750.89481021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-B57:02KKVSIGKGSLW0.99740.96621021
DNAJC3-FOXN3chr1396377506chr1489817152491HLA-A32:01KKVSIGKGSLW0.99430.96411021

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Potential FusionNeoAntigen Information of DNAJC3-FOXN3 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.
DNAJC3-FOXN3_96377506_89817152.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)
DNAJC3-FOXN3chr1396377506chr1489817152491DRB1-0454AEDDFKKVSIGKGSL520

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Fusion breakpoint peptide structures of DNAJC3-FOXN3

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
1576EDDFKKVSIGKGSLDNAJC3FOXN3chr1396377506chr1489817152491

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DNAJC3-FOXN3

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-B14:023BVN1576EDDFKKVSIGKGSL-7.15543-7.26883
HLA-B14:023BVN1576EDDFKKVSIGKGSL-4.77435-5.80965
HLA-B52:013W391576EDDFKKVSIGKGSL-6.80875-6.92215
HLA-B52:013W391576EDDFKKVSIGKGSL-4.20386-5.23916
HLA-A11:014UQ21576EDDFKKVSIGKGSL-7.5194-8.5547
HLA-A11:014UQ21576EDDFKKVSIGKGSL-6.9601-7.0735
HLA-A24:025HGA1576EDDFKKVSIGKGSL-7.52403-7.63743
HLA-A24:025HGA1576EDDFKKVSIGKGSL-5.82433-6.85963
HLA-B27:056PYJ1576EDDFKKVSIGKGSL-3.28285-4.31815
HLA-B44:053DX81576EDDFKKVSIGKGSL-5.91172-6.94702
HLA-B44:053DX81576EDDFKKVSIGKGSL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of DNAJC3-FOXN3

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
DNAJC3-FOXN3chr1396377506chr14898171521021KKVSIGKGSLWAAAAAAGTGAGTATTGGGAAAGGGTCGTTGTGG
DNAJC3-FOXN3chr1396377506chr14898171521121KVSIGKGSLWAAAGTGAGTATTGGGAAAGGGTCGTTGTGG
DNAJC3-FOXN3chr1396377506chr14898171521221VSIGKGSLWGTGAGTATTGGGAAAGGGTCGTTGTGG
DNAJC3-FOXN3chr1396377506chr1489817152514AEDDFKKVSGCAGAAGATGATTTTAAAAAAGTGAGT
DNAJC3-FOXN3chr1396377506chr1489817152515AEDDFKKVSIGCAGAAGATGATTTTAAAAAAGTGAGTATT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
DNAJC3-FOXN3chr1396377506chr1489817152520AEDDFKKVSIGKGSLGCAGAAGATGATTTTAAAAAAGTGAGTATTGGGAAAGGGTCGTTG

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Information of the samples that have these potential fusion neoantigens of DNAJC3-FOXN3

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
HNSCDNAJC3-FOXN3chr1396377506ENST00000376795chr1489817152ENST00000261302TCGA-CV-7438

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Potential target of CAR-T therapy development for DNAJC3-FOXN3

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 DNAJC3-FOXN3

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 DNAJC3-FOXN3

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