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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:ZNF595-WHSC1L1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZNF595-WHSC1L1
FusionPDB ID: 102506
FusionGDB2.0 ID: 102506
HgeneTgene
Gene symbol

ZNF595

WHSC1L1

Gene ID

152687

54904

Gene namezinc finger protein 595nuclear receptor binding SET domain protein 3
Synonyms-KMT3F|KMT3G|WHISTLE|WHSC1L1|pp14328
Cytomap

4p16.3

8p11.23

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein 595histone-lysine N-methyltransferase NSD3WHSC1-like 1 isoform 9 with methyltransferase activity to lysineWolf-Hirschhorn syndrome candidate 1-like 1nuclear SET domain-containing protein 3protein whistle
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000339368, ENST00000509152, 
ENST00000526473, 
ENST00000316985, 
ENST00000317025, ENST00000433384, 
ENST00000527502, ENST00000525081, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=814 X 10 X 9=1260
# samples 217
** MAII scorelog2(2/8*10)=1.32192809488736log2(17/1260*10)=-2.88981708224958
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZNF595 [Title/Abstract] AND WHSC1L1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZNF595 [Title/Abstract] AND WHSC1L1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZNF595(60046)-WHSC1L1(38205661), # samples:1
Anticipated loss of major functional domain due to fusion event.ZNF595-WHSC1L1 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.
ZNF595-WHSC1L1 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.
ZNF595-WHSC1L1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
ZNF595-WHSC1L1 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
ZNF595-WHSC1L1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
ZNF595-WHSC1L1 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
TgeneWHSC1L1

GO:0016571

histone methylation

16682010



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/chr4:60046/chr8:38205661)
- 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 ZNF595 (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 WHSC1L1 (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)
ENST00000509152ZNF595chr460046+ENST00000317025WHSC1L1chr838205661-10641411903410395453
ENST00000509152ZNF595chr460046+ENST00000433384WHSC1L1chr838205661-516541135584919453
ENST00000509152ZNF595chr460046+ENST00000527502WHSC1L1chr838205661-476241131554516453
ENST00000509152ZNF595chr460046+ENST00000316985WHSC1L1chr838205661-386041122533614453

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
ENST00000509152ENST00000317025ZNF595chr460046+WHSC1L1chr838205661-0.43576760.5642324
ENST00000509152ENST00000433384ZNF595chr460046+WHSC1L1chr838205661-0.0054031890.99459684
ENST00000509152ENST00000527502ZNF595chr460046+WHSC1L1chr838205661-0.0088998270.99110013
ENST00000509152ENST00000316985ZNF595chr460046+WHSC1L1chr838205661-0.0042799190.9957201

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 ZNF595-WHSC1L1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZNF595chr460046WHSC1L1chr838205661411320KPREEPVLKEEAPGSWETQFSNHLNS

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Potential FusionNeoAntigen Information of ZNF595-WHSC1L1 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.
ZNF595-WHSC1L1_60046_38205661.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)
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:03KEEAPGSW0.99930.9907816
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:01APGSWETQF0.98020.84561120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B45:01EEAPGSWET0.97050.9792918
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:08APGSWETQF0.95690.80911120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B50:02EEAPGSWET0.9320.7748918
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:05APGSWETQF0.91290.61251120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B41:01EEAPGSWET0.22380.9705918
ZNF595-WHSC1L1chr460046chr838205661411HLA-B82:01APGSWETQF0.0110.73751120
ZNF595-WHSC1L1chr460046chr838205661411HLA-A32:13VLKEEAPGSW0.70430.99616
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:03EEAPGSWETQF0.99950.9374920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B18:01EEAPGSWETQF0.95690.5981920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:09EEAPGSWETQF0.99940.5275920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:08EEAPGSWETQF0.99930.5085920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:10EEAPGSWETQF0.99450.6773920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:13KEEAPGSW0.99930.9907816
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:26KEEAPGSW0.99930.9907816
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:07KEEAPGSW0.99930.9907816
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:77APGSWETQF0.98020.84561120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:23APGSWETQF0.97850.85351120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:17APGSWETQF0.92930.75191120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:30APGSWETQF0.92930.75191120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:11APGSWETQF0.87140.84571120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:24APGSWETQF0.81920.84741120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B67:01APGSWETQF0.13620.83451120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B35:43APGSWETQF0.10040.8661120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B15:11APGSWETQF0.07290.85841120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B82:02APGSWETQF0.0110.73751120
ZNF595-WHSC1L1chr460046chr838205661411HLA-B15:24VLKEEAPGSW0.99940.9921616
ZNF595-WHSC1L1chr460046chr838205661411HLA-A25:01EAPGSWETQF0.90940.88171020
ZNF595-WHSC1L1chr460046chr838205661411HLA-B15:13VLKEEAPGSW0.89690.9656616
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:26EEAPGSWETQF0.99950.9374920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:13EEAPGSWETQF0.99950.9374920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B44:07EEAPGSWETQF0.99950.9374920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B18:11EEAPGSWETQF0.99570.5779920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B18:04EEAPGSWETQF0.97230.6149920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B18:06EEAPGSWETQF0.96020.6689920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B18:08EEAPGSWETQF0.95880.7577920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B18:05EEAPGSWETQF0.95690.5981920
ZNF595-WHSC1L1chr460046chr838205661411HLA-B18:03EEAPGSWETQF0.94640.5855920

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Potential FusionNeoAntigen Information of ZNF595-WHSC1L1 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 ZNF595-WHSC1L1

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
10078VLKEEAPGSWETQFZNF595WHSC1L1chr460046chr838205661411

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZNF595-WHSC1L1

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-B14:023BVN10078VLKEEAPGSWETQF-7.9962-8.1096
HLA-B14:023BVN10078VLKEEAPGSWETQF-5.70842-6.74372
HLA-B52:013W3910078VLKEEAPGSWETQF-6.83737-6.95077
HLA-B52:013W3910078VLKEEAPGSWETQF-4.4836-5.5189
HLA-A11:014UQ210078VLKEEAPGSWETQF-10.0067-10.1201
HLA-A11:014UQ210078VLKEEAPGSWETQF-9.03915-10.0745
HLA-A24:025HGA10078VLKEEAPGSWETQF-6.56204-6.67544
HLA-A24:025HGA10078VLKEEAPGSWETQF-5.42271-6.45801
HLA-B44:053DX810078VLKEEAPGSWETQF-7.85648-8.89178
HLA-B44:053DX810078VLKEEAPGSWETQF-5.3978-5.5112
HLA-B35:011A1N10078VLKEEAPGSWETQF-6.27422-6.38762
HLA-B35:011A1N10078VLKEEAPGSWETQF-5.27424-6.30954
HLA-A02:016TDR10078VLKEEAPGSWETQF-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ZNF595-WHSC1L1

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
ZNF595-WHSC1L1chr460046chr8382056611020EAPGSWETQFAACCCCCAGGGTCGGCGGACCGGGGAGTGC
ZNF595-WHSC1L1chr460046chr8382056611120APGSWETQFCCCCAGGGTCGGCGGACCGGGGAGTGC
ZNF595-WHSC1L1chr460046chr838205661616VLKEEAPGSWAGACAGCAGCCAAACCCCCAGGGTCGGCGG
ZNF595-WHSC1L1chr460046chr838205661816KEEAPGSWCAGCCAAACCCCCAGGGTCGGCGG
ZNF595-WHSC1L1chr460046chr838205661918EEAPGSWETCCAAACCCCCAGGGTCGGCGGACCGGG
ZNF595-WHSC1L1chr460046chr838205661920EEAPGSWETQFCCAAACCCCCAGGGTCGGCGGACCGGGGAGTGC

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 ZNF595-WHSC1L1

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
STADZNF595-WHSC1L1chr460046ENST00000509152chr838205661ENST00000316985TCGA-BR-8295-01A

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Potential target of CAR-T therapy development for ZNF595-WHSC1L1

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 ZNF595-WHSC1L1

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 ZNF595-WHSC1L1

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