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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:DHX58-FAM134C

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DHX58-FAM134C
FusionPDB ID: 22703
FusionGDB2.0 ID: 22703
HgeneTgene
Gene symbol

DHX58

FAM134C

Gene ID

79132

162427

Gene nameDExH-box helicase 58reticulophagy regulator family member 3
SynonymsD11LGP2|D11lgp2e|LGP2|RLR-3FAM134C
Cytomap

17q21.2

17q21.2

Type of geneprotein-codingprotein-coding
Descriptionprobable ATP-dependent RNA helicase DHX58DEXH (Asp-Glu-X-His) box polypeptide 58RIG-I-like receptor 3RIG-I-like receptor LGP2RLRRNA helicase LGP2ortholog of mouse D11lgp2probable ATP-dependent helicase LGP2protein D11Lgp2 homologreticulophagy regulator 3family with sequence similarity 134 member Cprotein FAM134C
Modification date2020032220200327
UniProtAcc

Q96C10

Main function of 5'-partner protein: FUNCTION: Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on DDX58/RIG-I signaling may involve the following mechanisms: competition with DDX58/RIG-I for binding to the viral RNA, binding to DDX58/RIG-I and inhibiting its dimerization and interaction with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1 thereby inhibiting activation of interferon regulatory factor 3 (IRF3). Its positive regulatory role may involve unwinding or stripping nucleoproteins of viral RNA thereby facilitating their recognition by DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses and coronavirus SARS-CoV-2, and also to the bacterial pathogen Listeria monocytogenes (PubMed:31256877). Can bind both ssRNA and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5'-triphosphorylated RNA, although it can recognize RNA lacking a 5'-triphosphate. {ECO:0000269|PubMed:16116171, ECO:0000269|PubMed:17020950, ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18411269, ECO:0000269|PubMed:19208642, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19278996, ECO:0000269|PubMed:19380577, ECO:0000269|PubMed:21187438, ECO:0000269|PubMed:21525357, ECO:0000269|PubMed:31256877}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000251642, ENST00000543197, 
ENST00000309428, ENST00000585894, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 2=1813 X 10 X 6=780
# samples 316
** MAII scorelog2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(16/780*10)=-2.28540221886225
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DHX58 [Title/Abstract] AND FAM134C [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DHX58 [Title/Abstract] AND FAM134C [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DHX58(40263314)-FAM134C(40739882), # samples:1
Anticipated loss of major functional domain due to fusion event.DHX58-FAM134C 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.
DHX58-FAM134C 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.
DHX58-FAM134C 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.
DHX58-FAM134C 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
HgeneDHX58

GO:0032480

negative regulation of type I interferon production

21525357

HgeneDHX58

GO:0039536

negative regulation of RIG-I signaling pathway

18411269

HgeneDHX58

GO:0045088

regulation of innate immune response

18411269

HgeneDHX58

GO:0045824

negative regulation of innate immune response

21525357



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/chr17:40263314/chr17:40739882)
- 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 DHX58 (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 FAM134C (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)
ENST00000251642DHX58chr1740263314-ENST00000309428FAM134Cchr1740739882-39465932231647474
ENST00000251642DHX58chr1740263314-ENST00000585894FAM134Cchr1740739882-21325932231647474

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
ENST00000251642ENST00000309428DHX58chr1740263314-FAM134Cchr1740739882-0.0179847260.98201525
ENST00000251642ENST00000585894DHX58chr1740263314-FAM134Cchr1740739882-0.0506173040.9493827

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 DHX58-FAM134C

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DHX58chr1740263314FAM134Cchr1740739882593123LTSPEEEEHVELTVPRPDALDNESWG

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Potential FusionNeoAntigen Information of DHX58-FAM134C 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.
DHX58-FAM134C_40263314_40739882.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)
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B18:01EEHVELTV0.98210.9781614
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B45:01EEEHVELTV0.99890.9379514
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B45:01EEHVELTVP0.99750.9222615
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B50:02EEHVELTVP0.9910.7861615
DHX58-FAM134Cchr1740263314chr1740739882593HLA-A33:05EHVELTVPR0.98960.7578716
DHX58-FAM134Cchr1740263314chr1740739882593HLA-A33:01EHVELTVPR0.98960.7578716
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B50:02EEEHVELTV0.98710.7405514
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B41:01EEHVELTVP0.73490.9324615
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B50:01EEHVELTVP0.4930.815615
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B45:01EEEEHVELTV0.99630.9539414
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C01:17TVPRPDAL0.9970.93391220
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B51:07EEHVELTV0.99140.9898614
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C01:30TVPRPDAL0.99020.94071220
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:19LTVPRPDAL0.99890.98871120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:07LTVPRPDAL0.99890.98251120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:08LTVPRPDAL0.99880.89981120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C15:04LTVPRPDAL0.99870.93341120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C15:06LTVPRPDAL0.9980.93611120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C04:06LTVPRPDAL0.98560.96391120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C12:12LTVPRPDAL0.98540.94731120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B40:06EEHVELTVP0.98470.6845615
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C06:03LTVPRPDAL0.97950.99471120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C12:04LTVPRPDAL0.97760.99541120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C08:13LTVPRPDAL0.97190.98971120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C08:04LTVPRPDAL0.97190.98971120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B44:10EEEHVELTV0.91920.7634514
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C02:06LTVPRPDAL0.90580.97751120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C01:17LTVPRPDAL0.86440.96721120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:14LTVPRPDAL0.7870.98641120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C08:03LTVPRPDAL0.76350.99461120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C01:30LTVPRPDAL0.71810.96651120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C01:02TVPRPDAL0.99710.93171220
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B18:05EEHVELTV0.98210.9781614
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C01:03TVPRPDAL0.97860.94031220
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B18:06EEHVELTV0.97730.9823614
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B18:03EEHVELTV0.95940.9766614
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:03LTVPRPDAL0.99890.98981120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:04LTVPRPDAL0.99890.98981120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C15:09LTVPRPDAL0.99870.93341120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:67LTVPRPDAL0.99820.98261120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C15:05LTVPRPDAL0.99790.91151120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C15:02LTVPRPDAL0.99760.90261120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:17LTVPRPDAL0.99760.97421120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:05LTVPRPDAL0.99760.93351120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:02LTVPRPDAL0.99280.98161120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C12:03LTVPRPDAL0.98340.98731120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C16:04LTVPRPDAL0.9810.98461120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C03:06LTVPRPDAL0.97540.99131120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C16:02LTVPRPDAL0.92150.99251120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C16:01LTVPRPDAL0.9170.98761120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C12:02LTVPRPDAL0.88220.97741120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C01:02LTVPRPDAL0.87990.96561120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B08:12LTVPRPDAL0.8790.53231120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C01:03LTVPRPDAL0.86230.95391120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C08:01LTVPRPDAL0.76350.99461120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B07:13LTVPRPDAL0.67920.89931120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B35:13LTVPRPDAL0.6790.90961120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B18:03EEEHVELTV0.60860.9695514
DHX58-FAM134Cchr1740263314chr1740739882593HLA-C17:01LTVPRPDAL0.54640.96611120
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B50:04EEHVELTVP0.4930.815615
DHX58-FAM134Cchr1740263314chr1740739882593HLA-B50:05EEHVELTVP0.4930.815615

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Potential FusionNeoAntigen Information of DHX58-FAM134C 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 DHX58-FAM134C

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
1665EEHVELTVPRPDALDHX58FAM134Cchr1740263314chr1740739882593

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DHX58-FAM134C

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-B14:023BVN1665EEHVELTVPRPDAL-7.75776-7.86956
HLA-B14:023BVN1665EEHVELTVPRPDAL-4.52646-5.56956
HLA-B52:013W391665EEHVELTVPRPDAL-7.1873-7.2991
HLA-B52:013W391665EEHVELTVPRPDAL-2.81174-3.85484
HLA-A11:014UQ21665EEHVELTVPRPDAL-5.13576-5.24756
HLA-A24:025HGA1665EEHVELTVPRPDAL-8.42076-8.53256
HLA-A24:025HGA1665EEHVELTVPRPDAL-7.10496-8.14806
HLA-B27:056PYJ1665EEHVELTVPRPDAL-9.28296-9.39476
HLA-B44:053DX81665EEHVELTVPRPDAL-6.88262-6.99442
HLA-B44:053DX81665EEHVELTVPRPDAL-5.46822-6.51132

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Vaccine Design for the FusionNeoAntigens of DHX58-FAM134C

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
DHX58-FAM134Cchr1740263314chr17407398821120LTVPRPDALTCACTGTGCCAAGACCCGACGCATTAG
DHX58-FAM134Cchr1740263314chr17407398821220TVPRPDALCTGTGCCAAGACCCGACGCATTAG
DHX58-FAM134Cchr1740263314chr1740739882414EEEEHVELTVAGGAGGAGGAGCACGTGGAGCTCACTGTGC
DHX58-FAM134Cchr1740263314chr1740739882514EEEHVELTVAGGAGGAGCACGTGGAGCTCACTGTGC
DHX58-FAM134Cchr1740263314chr1740739882614EEHVELTVAGGAGCACGTGGAGCTCACTGTGC
DHX58-FAM134Cchr1740263314chr1740739882615EEHVELTVPAGGAGCACGTGGAGCTCACTGTGCCAA
DHX58-FAM134Cchr1740263314chr1740739882716EHVELTVPRAGCACGTGGAGCTCACTGTGCCAAGAC

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 DHX58-FAM134C

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
STADDHX58-FAM134Cchr1740263314ENST00000251642chr1740739882ENST00000309428TCGA-BR-8487-01A

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Potential target of CAR-T therapy development for DHX58-FAM134C

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
TgeneFAM134Cchr17:40263314chr17:40739882ENST0000030942819164_1840467.0TransmembraneHelical
TgeneFAM134Cchr17:40263314chr17:40739882ENST0000030942819187_2070467.0TransmembraneHelical

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 DHX58-FAM134C

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 DHX58-FAM134C

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