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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:CRLS1-NFX1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CRLS1-NFX1
FusionPDB ID: 19520
FusionGDB2.0 ID: 19520
HgeneTgene
Gene symbol

CRLS1

NFX1

Gene ID

54675

4799

Gene namecardiolipin synthase 1nuclear transcription factor, X-box binding 1
SynonymsC20orf155|CLS|CLS1|GCD10|dJ967N21.6NFX2|TEG-42|Tex42
Cytomap

20p12.3

9p13.3

Type of geneprotein-codingprotein-coding
Descriptioncardiolipin synthase (CMP-forming)transcriptional repressor NF-X1nuclear transcription factor, X box-binding protein 1
Modification date2020031320200313
UniProtAcc

Q9UJA2

Main function of 5'-partner protein: FUNCTION: Catalyzes the synthesis of cardiolipin (CL) (diphosphatidylglycerol) by specifically transferring a phosphatidyl group from CDP-diacylglycerol to phosphatidylglycerol (PG). CL is a key phospholipid in mitochondrial membranes and plays important roles in maintaining the functional integrity and dynamics of mitochondria under both optimal and stress conditions. {ECO:0000269|PubMed:16547353, ECO:0000269|PubMed:16678169}.

ZNFX1

Main function of 5'-partner protein: 1918
Ensembl transtripts involved in fusion geneENST idsENST00000378863, ENST00000378868, 
ENST00000452938, ENST00000464921, 
ENST00000463421, ENST00000318524, 
ENST00000379521, ENST00000379540, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 8 X 5=32014 X 12 X 9=1512
# samples 815
** MAII scorelog2(8/320*10)=-2
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1512*10)=-3.33342373372519
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CRLS1 [Title/Abstract] AND NFX1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CRLS1 [Title/Abstract] AND NFX1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CRLS1(5996136)-NFX1(33328579), # samples:3
Anticipated loss of major functional domain due to fusion event.CRLS1-NFX1 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.
CRLS1-NFX1 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.
CRLS1-NFX1 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.
CRLS1-NFX1 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
TgeneNFX1

GO:0000122

negative regulation of transcription by RNA polymerase II

7964459

TgeneNFX1

GO:0051865

protein autoubiquitination

10500182



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/chr20:5996136/chr9:33328579)
- 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 CRLS1 (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 NFX1 (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)
ENST00000378863CRLS1chr205996136+ENST00000379540NFX1chr933328579+33677311572187676
ENST00000378863CRLS1chr205996136+ENST00000379521NFX1chr933328579+23737311571899580
ENST00000378863CRLS1chr205996136+ENST00000318524NFX1chr933328579+23107311571326389
ENST00000452938CRLS1chr205996136+ENST00000379540NFX1chr933328579+3307671972127676
ENST00000452938CRLS1chr205996136+ENST00000379521NFX1chr933328579+2313671971839580
ENST00000452938CRLS1chr205996136+ENST00000318524NFX1chr933328579+2250671971266389
ENST00000378868CRLS1chr205996136+ENST00000379540NFX1chr933328579+30634271501883577
ENST00000378868CRLS1chr205996136+ENST00000379521NFX1chr933328579+20694271501595481
ENST00000378868CRLS1chr205996136+ENST00000318524NFX1chr933328579+20064271501022290

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
ENST00000378863ENST00000379540CRLS1chr205996136+NFX1chr933328579+0.0077193780.9922806
ENST00000378863ENST00000379521CRLS1chr205996136+NFX1chr933328579+0.0137431090.9862569
ENST00000378863ENST00000318524CRLS1chr205996136+NFX1chr933328579+0.077488670.92251134
ENST00000452938ENST00000379540CRLS1chr205996136+NFX1chr933328579+0.0088853960.9911146
ENST00000452938ENST00000379521CRLS1chr205996136+NFX1chr933328579+0.0174788070.98252124
ENST00000452938ENST00000318524CRLS1chr205996136+NFX1chr933328579+0.083883780.91611624
ENST00000378868ENST00000379540CRLS1chr205996136+NFX1chr933328579+0.0032394890.99676055
ENST00000378868ENST00000379521CRLS1chr205996136+NFX1chr933328579+0.0037700570.99622995
ENST00000378868ENST00000318524CRLS1chr205996136+NFX1chr933328579+0.0069043390.9930957

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 CRLS1-NFX1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CRLS1chr205996136NFX1chr93332857942790ISILYVSLTYADLIPDFIHTCEKLCH
CRLS1chr205996136NFX1chr933328579671189ISILYVSLTYADLIPDFIHTCEKLCH
CRLS1chr205996136NFX1chr933328579731189ISILYVSLTYADLIPDFIHTCEKLCH

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Potential FusionNeoAntigen Information of CRLS1-NFX1 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.
CRLS1-NFX1_5996136_33328579.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)
CRLS1-NFX1chr205996136chr933328579731HLA-A02:21LIPDFIHTC0.85390.63861221
CRLS1-NFX1chr205996136chr933328579731HLA-A24:14SLTYADLIPDF0.79210.5184617
CRLS1-NFX1chr205996136chr933328579731HLA-C04:10YADLIPDF10.6706917
CRLS1-NFX1chr205996136chr933328579731HLA-C05:09YADLIPDF10.9422917
CRLS1-NFX1chr205996136chr933328579731HLA-C08:15YADLIPDF0.99990.9626917
CRLS1-NFX1chr205996136chr933328579731HLA-C04:07YADLIPDF0.99990.69917
CRLS1-NFX1chr205996136chr933328579731HLA-C04:06YADLIPDF0.99770.769917
CRLS1-NFX1chr205996136chr933328579731HLA-C08:13YADLIPDF0.99420.962917
CRLS1-NFX1chr205996136chr933328579731HLA-C08:04YADLIPDF0.99420.962917
CRLS1-NFX1chr205996136chr933328579731HLA-C08:03YADLIPDF0.91550.9746917
CRLS1-NFX1chr205996136chr933328579731HLA-C05:09YADLIPDFI0.9990.9412918
CRLS1-NFX1chr205996136chr933328579731HLA-C04:10YADLIPDFI0.99880.6575918
CRLS1-NFX1chr205996136chr933328579731HLA-C04:07YADLIPDFI0.99870.6853918
CRLS1-NFX1chr205996136chr933328579731HLA-C08:15YADLIPDFI0.99740.9566918
CRLS1-NFX1chr205996136chr933328579731HLA-C04:06YADLIPDFI0.9540.7532918
CRLS1-NFX1chr205996136chr933328579731HLA-A02:07LIPDFIHTC0.82880.57781221
CRLS1-NFX1chr205996136chr933328579731HLA-C08:13YADLIPDFI0.76470.9498918
CRLS1-NFX1chr205996136chr933328579731HLA-C08:04YADLIPDFI0.76470.9498918
CRLS1-NFX1chr205996136chr933328579731HLA-B15:21TYADLIPDF0.72580.9378817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:29TYADLIPDF0.59950.9176817
CRLS1-NFX1chr205996136chr933328579731HLA-C04:14YADLIPDFI0.58450.6384918
CRLS1-NFX1chr205996136chr933328579731HLA-C07:05TYADLIPDF0.55750.9643817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:13TYADLIPDF0.51860.9251817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:10TYADLIPDF0.50110.9678817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:80TYADLIPDF0.49210.9593817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:67TYADLIPDF0.49210.9593817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:19TYADLIPDF0.48150.7788817
CRLS1-NFX1chr205996136chr933328579731HLA-C08:03YADLIPDFI0.47740.9667918
CRLS1-NFX1chr205996136chr933328579731HLA-C07:46TYADLIPDF0.46990.9138817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:95TYADLIPDF0.42480.6799817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:27TYADLIPDF0.42020.9554817
CRLS1-NFX1chr205996136chr933328579731HLA-C12:16TYADLIPDF0.39640.956817
CRLS1-NFX1chr205996136chr933328579731HLA-C04:10TYADLIPDF0.3370.7448817
CRLS1-NFX1chr205996136chr933328579731HLA-C04:07TYADLIPDF0.32870.7633817
CRLS1-NFX1chr205996136chr933328579731HLA-C01:30LIPDFIHTC0.11940.95451221
CRLS1-NFX1chr205996136chr933328579731HLA-C04:14TYADLIPDF0.11440.7189817
CRLS1-NFX1chr205996136chr933328579731HLA-C01:17LIPDFIHTC0.0960.93861221
CRLS1-NFX1chr205996136chr933328579731HLA-C02:06YADLIPDFI0.09240.9328918
CRLS1-NFX1chr205996136chr933328579731HLA-C04:03YADLIPDF10.7547917
CRLS1-NFX1chr205996136chr933328579731HLA-C05:01YADLIPDF10.9422917
CRLS1-NFX1chr205996136chr933328579731HLA-C08:02YADLIPDF0.99990.9626917
CRLS1-NFX1chr205996136chr933328579731HLA-C18:01YADLIPDF0.99990.7727917
CRLS1-NFX1chr205996136chr933328579731HLA-C04:01YADLIPDF0.99990.69917
CRLS1-NFX1chr205996136chr933328579731HLA-C08:01YADLIPDF0.91550.9746917
CRLS1-NFX1chr205996136chr933328579731HLA-C04:03YADLIPDFI0.99910.7476918
CRLS1-NFX1chr205996136chr933328579731HLA-C05:01YADLIPDFI0.9990.9412918
CRLS1-NFX1chr205996136chr933328579731HLA-C04:01YADLIPDFI0.99870.6853918
CRLS1-NFX1chr205996136chr933328579731HLA-C18:01YADLIPDFI0.99850.7429918
CRLS1-NFX1chr205996136chr933328579731HLA-C08:02YADLIPDFI0.99740.9566918
CRLS1-NFX1chr205996136chr933328579731HLA-C15:05YADLIPDFI0.97130.9078918
CRLS1-NFX1chr205996136chr933328579731HLA-C04:04YADLIPDFI0.8870.7247918
CRLS1-NFX1chr205996136chr933328579731HLA-A02:14LIPDFIHTC0.85670.54691221
CRLS1-NFX1chr205996136chr933328579731HLA-A02:06LIPDFIHTC0.85390.63861221
CRLS1-NFX1chr205996136chr933328579731HLA-C03:06YADLIPDFI0.80130.9813918
CRLS1-NFX1chr205996136chr933328579731HLA-C03:67TYADLIPDF0.59740.9838817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:17TYADLIPDF0.52940.9625817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:02TYADLIPDF0.49210.9593817
CRLS1-NFX1chr205996136chr933328579731HLA-C08:01YADLIPDFI0.47740.9667918
CRLS1-NFX1chr205996136chr933328579731HLA-C07:01TYADLIPDF0.410.6865817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:22TYADLIPDF0.40060.6834817
CRLS1-NFX1chr205996136chr933328579731HLA-C04:01TYADLIPDF0.32870.7633817
CRLS1-NFX1chr205996136chr933328579731HLA-C17:01YADLIPDFI0.31420.7979918
CRLS1-NFX1chr205996136chr933328579731HLA-C18:01TYADLIPDF0.26080.8267817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:04YADLIPDFI0.24030.8962918
CRLS1-NFX1chr205996136chr933328579731HLA-C14:02TYADLIPDF0.23190.9654817
CRLS1-NFX1chr205996136chr933328579731HLA-C14:03TYADLIPDF0.23190.9654817
CRLS1-NFX1chr205996136chr933328579731HLA-C01:03LIPDFIHTC0.14780.84781221
CRLS1-NFX1chr205996136chr933328579731HLA-C04:04TYADLIPDF0.12140.8117817
CRLS1-NFX1chr205996136chr933328579731HLA-C07:04TYADLIPDF0.08050.9507817
CRLS1-NFX1chr205996136chr933328579731HLA-C01:02LIPDFIHTC0.07490.9361221
CRLS1-NFX1chr205996136chr933328579731HLA-C06:06TYADLIPDF0.04420.9875817
CRLS1-NFX1chr205996136chr933328579731HLA-B07:13YADLIPDFI0.00430.6709918

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Potential FusionNeoAntigen Information of CRLS1-NFX1 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 CRLS1-NFX1

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
8805SLTYADLIPDFIHTCRLS1NFX1chr205996136chr933328579731

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CRLS1-NFX1

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-B14:023BVN8805SLTYADLIPDFIHT-7.15543-7.26883
HLA-B14:023BVN8805SLTYADLIPDFIHT-4.77435-5.80965
HLA-B52:013W398805SLTYADLIPDFIHT-6.80875-6.92215
HLA-B52:013W398805SLTYADLIPDFIHT-4.20386-5.23916
HLA-A11:014UQ28805SLTYADLIPDFIHT-7.5194-8.5547
HLA-A11:014UQ28805SLTYADLIPDFIHT-6.9601-7.0735
HLA-A24:025HGA8805SLTYADLIPDFIHT-7.52403-7.63743
HLA-A24:025HGA8805SLTYADLIPDFIHT-5.82433-6.85963
HLA-B27:056PYJ8805SLTYADLIPDFIHT-3.28285-4.31815
HLA-B44:053DX88805SLTYADLIPDFIHT-5.91172-6.94702
HLA-B44:053DX88805SLTYADLIPDFIHT-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CRLS1-NFX1

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
CRLS1-NFX1chr205996136chr9333285791221LIPDFIHTCCAGATTTCATTCATACCTGTGAAAAGC
CRLS1-NFX1chr205996136chr933328579617SLTYADLIPDFCCTATGCAGATCTTATTCCAGATTTCATTCATA
CRLS1-NFX1chr205996136chr933328579817TYADLIPDFCAGATCTTATTCCAGATTTCATTCATA
CRLS1-NFX1chr205996136chr933328579917YADLIPDFATCTTATTCCAGATTTCATTCATA
CRLS1-NFX1chr205996136chr933328579918YADLIPDFIATCTTATTCCAGATTTCATTCATACCT

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 CRLS1-NFX1

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
KIRCCRLS1-NFX1chr205996136ENST00000378863chr933328579ENST00000318524TCGA-BP-5199-01A

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Potential target of CAR-T therapy development for CRLS1-NFX1

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
HgeneCRLS1chr20:5996136chr9:33328579ENST00000378863+37109_129191302.0TransmembraneHelical
HgeneCRLS1chr20:5996136chr9:33328579ENST00000378863+37133_153191302.0TransmembraneHelical

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 CRLS1-NFX1

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 CRLS1-NFX1

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