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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:CASZ1-ALG14

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CASZ1-ALG14
FusionPDB ID: 13274
FusionGDB2.0 ID: 13274
HgeneTgene
Gene symbol

CASZ1

ALG14

Gene ID

54897

199857

Gene namecastor zinc finger 1ALG14 UDP-N-acetylglucosaminyltransferase subunit
SynonymsCAS11|CST|SRG|ZNF693|dJ734G22.1CMS15
Cytomap

1p36.22

1p21.3

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein castor homolog 1castor homolog 1, zinc fingercastor-related proteinsurvival-relatedzinc finger protein 693UDP-N-acetylglucosamine transferase subunit ALG14 homolog
Modification date2020031320200313
UniProtAcc

Q86V15

Main function of 5'-partner protein: FUNCTION: Transcriptional activator (PubMed:23639441, PubMed:27693370). Involved in vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7 (PubMed:23639441). {ECO:0000269|PubMed:23639441, ECO:0000269|PubMed:27693370}.

Q96F25

Main function of 5'-partner protein: FUNCTION: May be involved in protein N-glycosylation. May play a role in the second step of the dolichol-linked oligosaccharide pathway. May anchor the catalytic subunit ALG13 to the ER. {ECO:0000269|PubMed:16100110}.
Ensembl transtripts involved in fusion geneENST idsENST00000344008, ENST00000377022, 
ENST00000478728, 
ENST00000495856, 
ENST00000370205, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 19 X 12=52447 X 7 X 5=245
# samples 3010
** MAII scorelog2(30/5244*10)=-4.12763327972587
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/245*10)=-1.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CASZ1 [Title/Abstract] AND ALG14 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CASZ1 [Title/Abstract] AND ALG14 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CASZ1(10753931)-ALG14(95530573), # samples:1
Anticipated loss of major functional domain due to fusion event.CASZ1-ALG14 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.
CASZ1-ALG14 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
HgeneCASZ1

GO:0045893

positive regulation of transcription, DNA-templated

27693370



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/chr1:10753931/chr1:95530573)
- 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 CASZ1 (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 ALG14 (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)
ENST00000377022CASZ1chr110753931-ENST00000370205ALG14chr195530573-9518334285848187
ENST00000344008CASZ1chr110753931-ENST00000370205ALG14chr195530573-9520336287850187

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
ENST00000377022ENST00000370205CASZ1chr110753931-ALG14chr195530573-0.0072658790.9927341
ENST00000344008ENST00000370205CASZ1chr110753931-ALG14chr195530573-0.0072439340.99275607

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 CASZ1-ALG14

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CASZ1chr110753931ALG14chr19553057333416EFGTKEKRMDLGTGGHTTEILRLLGS
CASZ1chr110753931ALG14chr19553057333616EFGTKEKRMDLGTGGHTTEILRLLGS

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Potential FusionNeoAntigen Information of CASZ1-ALG14 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.
CASZ1-ALG14_10753931_95530573.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)
CASZ1-ALG14chr110753931chr195530573336HLA-B27:04KRMDLGTGGH0.99760.5372616
CASZ1-ALG14chr110753931chr195530573336HLA-B38:01TGGHTTEILRL0.60470.78671223
CASZ1-ALG14chr110753931chr195530573336HLA-B38:02TGGHTTEILRL0.54550.7981223
CASZ1-ALG14chr110753931chr195530573336HLA-B27:10KRMDLGTGGH0.99710.6641616
CASZ1-ALG14chr110753931chr195530573336HLA-B38:05TGGHTTEILRL0.60470.78671223

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Potential FusionNeoAntigen Information of CASZ1-ALG14 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 CASZ1-ALG14

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
4568KRMDLGTGGHTTEICASZ1ALG14chr110753931chr195530573336

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CASZ1-ALG14

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-B14:023BVN4568KRMDLGTGGHTTEI-5.94137-6.05477
HLA-B14:023BVN4568KRMDLGTGGHTTEI-3.60856-4.64386
HLA-B52:013W394568KRMDLGTGGHTTEI-4.51807-5.55337
HLA-B52:013W394568KRMDLGTGGHTTEI-4.45976-4.57316
HLA-B18:014JQV4568KRMDLGTGGHTTEI-5.40037-5.51377
HLA-A11:014UQ24568KRMDLGTGGHTTEI-10.8398-10.9532
HLA-A11:014UQ24568KRMDLGTGGHTTEI-8.18216-9.21746
HLA-A24:025HGA4568KRMDLGTGGHTTEI-7.96836-8.08176
HLA-A24:025HGA4568KRMDLGTGGHTTEI-5.58393-6.61923
HLA-B27:056PYJ4568KRMDLGTGGHTTEI-6.27024-7.30554
HLA-B27:056PYJ4568KRMDLGTGGHTTEI-3.2812-3.3946
HLA-B27:036PZ54568KRMDLGTGGHTTEI-3.93077-4.04417
HLA-B44:053DX84568KRMDLGTGGHTTEI-5.7294-5.8428
HLA-B44:053DX84568KRMDLGTGGHTTEI-3.42665-4.46195

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Vaccine Design for the FusionNeoAntigens of CASZ1-ALG14

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
CASZ1-ALG14chr110753931chr1955305731223TGGHTTEILRLCAGGTGGGCATACCACTGAGATCCTGAGGCTGC
CASZ1-ALG14chr110753931chr195530573616KRMDLGTGGHAGAGAATGGATCTTGGAACAGGTGGGCATA

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 CASZ1-ALG14

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
UCECCASZ1-ALG14chr110753931ENST00000344008chr195530573ENST00000370205TCGA-AX-A3G4-01A

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Potential target of CAR-T therapy development for CASZ1-ALG14

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 CASZ1-ALG14

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 CASZ1-ALG14

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