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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:HUWE1-WNK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HUWE1-WNK1
FusionPDB ID: 38120
FusionGDB2.0 ID: 38120
HgeneTgene
Gene symbol

HUWE1

WNK1

Gene ID

10075

65125

Gene nameHECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1WNK lysine deficient protein kinase 1
SynonymsARF-BP1|HECTH9|HSPC272|Ib772|LASU1|MRXST|MULE|URE-B1|UREB1HSAN2|HSN2|KDP|PPP1R167|PRKWNK1|PSK|p65
Cytomap

Xp11.22

12p13.33

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase HUWE1ARF-binding protein 1BJ-HCC-24 tumor antigenHECT domain protein LASU1HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligaseHECT-type E3 ubiquitin transferase HUWE1Mcl-1 ubiquitin ligase E3URE-binding proserine/threonine-protein kinase WNK1WNK lysine deficient protein kinase 1 isoformerythrocyte 65 kDa proteinprostate-derived sterile 20-like kinaseprotein kinase with no lysine 1protein phosphatase 1, regulatory subunit 167serine/threonine-protein ki
Modification date2020031320200327
UniProtAcc

Q7Z6Z7

Main function of 5'-partner protein: FUNCTION: E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15989957, PubMed:19713937, PubMed:15567145, PubMed:15767685, PubMed:18488021, PubMed:17567951, PubMed:19037095, PubMed:20534529). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). {ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000218328, ENST00000262854, 
ENST00000342160, ENST00000474288, 
ENST00000340908, ENST00000447667, 
ENST00000530271, ENST00000540360, 
ENST00000574564, ENST00000315939, 
ENST00000535572, ENST00000537687, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 22 X 7=261813 X 15 X 6=1170
# samples 2214
** MAII scorelog2(22/2618*10)=-3.57288966842058
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/1170*10)=-3.0630097975258
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HUWE1 [Title/Abstract] AND WNK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HUWE1 [Title/Abstract] AND WNK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HUWE1(53619357)-WNK1(992560), # samples:1
Anticipated loss of major functional domain due to fusion event.HUWE1-WNK1 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.
HUWE1-WNK1 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.
HUWE1-WNK1 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.
HUWE1-WNK1 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.
HUWE1-WNK1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
HUWE1-WNK1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
HUWE1-WNK1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
HUWE1-WNK1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
HUWE1-WNK1 seems lost the major protein functional domain in Tgene partner, which is a kinase 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
HgeneHUWE1

GO:0000209

protein polyubiquitination

15989957

HgeneHUWE1

GO:0006513

protein monoubiquitination

19713937

HgeneHUWE1

GO:0016574

histone ubiquitination

15767685

HgeneHUWE1

GO:0031398

positive regulation of protein ubiquitination

20534529

HgeneHUWE1

GO:0098779

positive regulation of mitophagy in response to mitochondrial depolarization

30217973

TgeneWNK1

GO:0006468

protein phosphorylation

10660600

TgeneWNK1

GO:0010923

negative regulation of phosphatase activity

19389623

TgeneWNK1

GO:0023016

signal transduction by trans-phosphorylation

16669787

TgeneWNK1

GO:0035556

intracellular signal transduction

10660600



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/chrX:53619357/chr12:992560)
- 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 HUWE1 (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 WNK1 (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)
ENST00000262854HUWE1chrX53619357-ENST00000535572WNK1chr12992560+10539437438780302547
ENST00000262854HUWE1chrX53619357-ENST00000537687WNK1chr12992560+10694437438780332548
ENST00000262854HUWE1chrX53619357-ENST00000315939WNK1chr12992560+10694437438780332548
ENST00000218328HUWE1chrX53619357-ENST00000535572WNK1chr12992560+10539437438780302547
ENST00000218328HUWE1chrX53619357-ENST00000537687WNK1chr12992560+10694437438780332548
ENST00000218328HUWE1chrX53619357-ENST00000315939WNK1chr12992560+10694437438780332548

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
ENST00000262854ENST00000535572HUWE1chrX53619357-WNK1chr12992560+0.0022885970.9977114
ENST00000262854ENST00000537687HUWE1chrX53619357-WNK1chr12992560+0.0021675260.9978325
ENST00000262854ENST00000315939HUWE1chrX53619357-WNK1chr12992560+0.0021675260.9978325
ENST00000218328ENST00000535572HUWE1chrX53619357-WNK1chr12992560+0.0022885970.9977114
ENST00000218328ENST00000537687HUWE1chrX53619357-WNK1chr12992560+0.0021675260.9978325
ENST00000218328ENST00000315939HUWE1chrX53619357-WNK1chr12992560+0.0021675260.9978325

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 HUWE1-WNK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HUWE1chrX53619357WNK1chr1299256043741326GGSRREPQVNQQQLQQVNNDFILAIE

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Potential FusionNeoAntigen Information of HUWE1-WNK1 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.
HUWE1-WNK1_53619357_992560.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)
HUWE1-WNK1chrX53619357chr129925604374HLA-B35:02EPQVNQQQL0.49640.717514
HUWE1-WNK1chrX53619357chr129925604374HLA-B35:04EPQVNQQQL0.49640.717514
HUWE1-WNK1chrX53619357chr129925604374HLA-B07:02REPQVNQQQL0.50130.5323414
HUWE1-WNK1chrX53619357chr129925604374HLA-B39:13REPQVNQQQL0.41450.9284414
HUWE1-WNK1chrX53619357chr129925604374HLA-B07:02RREPQVNQQQL0.94180.585314
HUWE1-WNK1chrX53619357chr129925604374HLA-B14:03EPQVNQQQL0.75390.7963514
HUWE1-WNK1chrX53619357chr129925604374HLA-B35:12EPQVNQQQL0.49640.717514
HUWE1-WNK1chrX53619357chr129925604374HLA-B42:02EPQVNQQQL0.2880.5185514
HUWE1-WNK1chrX53619357chr129925604374HLA-B39:10EPQVNQQQL0.24410.8148514
HUWE1-WNK1chrX53619357chr129925604374HLA-B42:01EPQVNQQQL0.19520.5086514
HUWE1-WNK1chrX53619357chr129925604374HLA-B39:08REPQVNQQQL0.76610.8279414
HUWE1-WNK1chrX53619357chr129925604374HLA-B07:04REPQVNQQQL0.7480.5069414
HUWE1-WNK1chrX53619357chr129925604374HLA-B07:12REPQVNQQQL0.71820.6039414
HUWE1-WNK1chrX53619357chr129925604374HLA-B42:02REPQVNQQQL0.47910.5791414
HUWE1-WNK1chrX53619357chr129925604374HLA-B42:01REPQVNQQQL0.42340.5675414
HUWE1-WNK1chrX53619357chr129925604374HLA-B44:10REPQVNQQQL0.22230.5309414
HUWE1-WNK1chrX53619357chr129925604374HLA-C07:95RREPQVNQQQL0.99450.5512314
HUWE1-WNK1chrX53619357chr129925604374HLA-B07:12RREPQVNQQQL0.97570.6716314
HUWE1-WNK1chrX53619357chr129925604374HLA-B35:09EPQVNQQQL0.49640.717514
HUWE1-WNK1chrX53619357chr129925604374HLA-B67:01EPQVNQQQL0.28510.7098514
HUWE1-WNK1chrX53619357chr129925604374HLA-B08:12EPQVNQQQL0.11690.6156514
HUWE1-WNK1chrX53619357chr129925604374HLA-B15:24QQLQQVNNDF0.99430.66851121
HUWE1-WNK1chrX53619357chr129925604374HLA-B40:04REPQVNQQQL0.78860.6828414
HUWE1-WNK1chrX53619357chr129925604374HLA-B07:22REPQVNQQQL0.50130.5323414
HUWE1-WNK1chrX53619357chr129925604374HLA-B41:03REPQVNQQQL0.40680.6674414
HUWE1-WNK1chrX53619357chr129925604374HLA-C07:01RREPQVNQQQL0.99530.5424314
HUWE1-WNK1chrX53619357chr129925604374HLA-C07:22RREPQVNQQQL0.97470.6414314
HUWE1-WNK1chrX53619357chr129925604374HLA-B07:22RREPQVNQQQL0.94180.585314

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Potential FusionNeoAntigen Information of HUWE1-WNK1 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.
HUWE1-WNK1_53619357_992560.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)
HUWE1-WNK1chrX53619357chr129925604374DRB4-0101EPQVNQQQLQQVNND520
HUWE1-WNK1chrX53619357chr129925604374DRB4-0101REPQVNQQQLQQVNN419
HUWE1-WNK1chrX53619357chr129925604374DRB4-0103EPQVNQQQLQQVNND520
HUWE1-WNK1chrX53619357chr129925604374DRB4-0103REPQVNQQQLQQVNN419
HUWE1-WNK1chrX53619357chr129925604374DRB4-0104EPQVNQQQLQQVNND520
HUWE1-WNK1chrX53619357chr129925604374DRB4-0104REPQVNQQQLQQVNN419
HUWE1-WNK1chrX53619357chr129925604374DRB4-0106EPQVNQQQLQQVNND520
HUWE1-WNK1chrX53619357chr129925604374DRB4-0106REPQVNQQQLQQVNN419
HUWE1-WNK1chrX53619357chr129925604374DRB4-0107EPQVNQQQLQQVNND520
HUWE1-WNK1chrX53619357chr129925604374DRB4-0107REPQVNQQQLQQVNN419
HUWE1-WNK1chrX53619357chr129925604374DRB4-0108EPQVNQQQLQQVNND520
HUWE1-WNK1chrX53619357chr129925604374DRB4-0108REPQVNQQQLQQVNN419

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Fusion breakpoint peptide structures of HUWE1-WNK1

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
6930PQVNQQQLQQVNNDHUWE1WNK1chrX53619357chr129925604374

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HUWE1-WNK1

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-B14:023BVN6930PQVNQQQLQQVNND-7.15543-7.26883
HLA-B14:023BVN6930PQVNQQQLQQVNND-4.77435-5.80965
HLA-B52:013W396930PQVNQQQLQQVNND-6.80875-6.92215
HLA-B52:013W396930PQVNQQQLQQVNND-4.20386-5.23916
HLA-A11:014UQ26930PQVNQQQLQQVNND-7.5194-8.5547
HLA-A11:014UQ26930PQVNQQQLQQVNND-6.9601-7.0735
HLA-A24:025HGA6930PQVNQQQLQQVNND-7.52403-7.63743
HLA-A24:025HGA6930PQVNQQQLQQVNND-5.82433-6.85963
HLA-B27:056PYJ6930PQVNQQQLQQVNND-3.28285-4.31815
HLA-B44:053DX86930PQVNQQQLQQVNND-5.91172-6.94702
HLA-B44:053DX86930PQVNQQQLQQVNND-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of HUWE1-WNK1

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
HUWE1-WNK1chrX53619357chr129925601121QQLQQVNNDFCAACAGGTGAACAATGACTTTATTCTAGCA
HUWE1-WNK1chrX53619357chr12992560314RREPQVNQQQLCCTCAAGTCAACCAGCAACAACTGCAACAGGTG
HUWE1-WNK1chrX53619357chr12992560414REPQVNQQQLCAAGTCAACCAGCAACAACTGCAACAGGTG
HUWE1-WNK1chrX53619357chr12992560514EPQVNQQQLGTCAACCAGCAACAACTGCAACAGGTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
HUWE1-WNK1chrX53619357chr12992560419REPQVNQQQLQQVNNCAAGTCAACCAGCAACAACTGCAACAGGTGAACAATGACTTTATT
HUWE1-WNK1chrX53619357chr12992560520EPQVNQQQLQQVNNDGTCAACCAGCAACAACTGCAACAGGTGAACAATGACTTTATTCTA

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Information of the samples that have these potential fusion neoantigens of HUWE1-WNK1

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
STADHUWE1-WNK1chrX53619357ENST00000218328chr12992560ENST00000315939TCGA-B7-A5TN

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Potential target of CAR-T therapy development for HUWE1-WNK1

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 HUWE1-WNK1

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 HUWE1-WNK1

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