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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:KDM6A-FUNDC1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KDM6A-FUNDC1
FusionPDB ID: 41903
FusionGDB2.0 ID: 41903
HgeneTgene
Gene symbol

KDM6A

FUNDC1

Gene ID

7403

139341

Gene namelysine demethylase 6AFUN14 domain containing 1
SynonymsKABUK2|UTX|bA386N14.2-
Cytomap

Xp11.3

Xp11.3

Type of geneprotein-codingprotein-coding
Descriptionlysine-specific demethylase 6AbA386N14.2 (ubiquitously transcribed X chromosome tetratricopeptide repeat protein (UTX))histone demethylase UTXlysine (K)-specific demethylase 6Aubiquitously transcribed tetratricopeptide repeat protein X-linkedubiquitoFUN14 domain-containing protein 1
Modification date2020031320200313
UniProtAcc

O15550

Main function of 5'-partner protein: FUNCTION: Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17851529, PubMed:17713478, PubMed:17761849). Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27' (PubMed:17851529, PubMed:17713478, PubMed:17761849). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A (PubMed:17761849). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (By similarity). {ECO:0000250|UniProtKB:O70546, ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17761849, ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914}.

Q8IVP5

Main function of 5'-partner protein: FUNCTION: Acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality control. {ECO:0000269|PubMed:22267086}.
Ensembl transtripts involved in fusion geneENST idsENST00000377967, ENST00000382899, 
ENST00000536777, ENST00000543216, 
ENST00000479423, 
ENST00000483115, 
ENST00000378045, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 9 X 11=18816 X 5 X 4=120
# samples 207
** MAII scorelog2(20/1881*10)=-3.23342794374847
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/120*10)=-0.777607578663552
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KDM6A [Title/Abstract] AND FUNDC1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KDM6A [Title/Abstract] AND FUNDC1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KDM6A(44833960)-FUNDC1(44401347), # samples:4
Anticipated loss of major functional domain due to fusion event.KDM6A-FUNDC1 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.
KDM6A-FUNDC1 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.
KDM6A-FUNDC1 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.
KDM6A-FUNDC1 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.
KDM6A-FUNDC1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
KDM6A-FUNDC1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
KDM6A-FUNDC1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
KDM6A-FUNDC1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
KDM6A-FUNDC1 seems lost the major protein functional domain in Hgene 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
TgeneFUNDC1

GO:0000422

autophagy of mitochondrion

22267086

TgeneFUNDC1

GO:0001666

response to hypoxia

22267086



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:44833960/chrX:44401347)
- 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 KDM6A (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 FUNDC1 (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)
ENST00000377967KDM6AchrX44833960+ENST00000378045FUNDC1chrX44386611-119142541631196
ENST00000382899KDM6AchrX44833960+ENST00000378045FUNDC1chrX44386611-116740117607196
ENST00000536777KDM6AchrX44833960+ENST00000378045FUNDC1chrX44386611-116740117607196
ENST00000543216KDM6AchrX44833960+ENST00000378045FUNDC1chrX44386611-11503840590196

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
ENST00000377967ENST00000378045KDM6AchrX44833960+FUNDC1chrX44386611-0.0005176960.9994823
ENST00000382899ENST00000378045KDM6AchrX44833960+FUNDC1chrX44386611-0.0004850630.99951494
ENST00000536777ENST00000378045KDM6AchrX44833960+FUNDC1chrX44386611-0.0004850630.99951494
ENST00000543216ENST00000378045KDM6AchrX44833960+FUNDC1chrX44386611-0.0004627680.9995372

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 KDM6A-FUNDC1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KDM6AchrX44833960FUNDC1chrX44386611384128YQRYYSLQSDYWKIASHSGYVQIDWK
KDM6AchrX44833960FUNDC1chrX44386611401128YQRYYSLQSDYWKIASHSGYVQIDWK
KDM6AchrX44833960FUNDC1chrX44386611425128YQRYYSLQSDYWKIASHSGYVQIDWK

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Potential FusionNeoAntigen Information of KDM6A-FUNDC1 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.
KDM6A-FUNDC1_44833960_44386611.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)
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-B52:01LQSDYWKI0.91080.9554614
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-A02:38KIASHSGYV0.98450.71711221
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-A02:13KIASHSGYV0.98010.67081221
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-A02:27KIASHSGYV0.96960.53961221
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-A02:21SLQSDYWKI0.89470.5455514
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-B15:18WKIASHSGY0.21880.59111120
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-B15:03WKIASHSGY0.13790.66451120
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-B13:02SLQSDYWKI0.05450.5049514
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-A02:03KIASHSGYV0.99260.65191221
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-A02:06SLQSDYWKI0.89470.5455514
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-B18:08SDYWKIASH0.20960.6224817
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-B48:02WKIASHSGY0.17940.83481120
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-B15:53WKIASHSGY0.15730.80761120
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-B15:54WKIASHSGY0.06920.79121120
KDM6A-FUNDC1chrX44833960chrX44386611425HLA-B15:54YWKIASHSGY0.83730.73171020

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Potential FusionNeoAntigen Information of KDM6A-FUNDC1 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.
KDM6A-FUNDC1_44833960_44386611.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)
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0431QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0443QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0447QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0447LQSDYWKIASHSGYV621
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0447SLQSDYWKIASHSGY520
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0454QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0454LQSDYWKIASHSGYV621
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0454SLQSDYWKIASHSGY520
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0475QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0482QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0482LQSDYWKIASHSGYV621
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0902QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-0903QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1130QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1130LQSDYWKIASHSGYV621
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1601QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1601LQSDYWKIASHSGYV621
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1602QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1603QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1603LQSDYWKIASHSGYV621
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1604QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1604LQSDYWKIASHSGYV621
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1605QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1607QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1608QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1608LQSDYWKIASHSGYV621
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1609QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1609LQSDYWKIASHSGYV621
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1610QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1611QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1612QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1614QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB1-1616QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB5-0102QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB5-0103QSDYWKIASHSGYVQ722
KDM6A-FUNDC1chrX44833960chrX44386611425DRB5-0108NQSDYWKIASHSGYVQ722

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Fusion breakpoint peptide structures of KDM6A-FUNDC1

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
5492LQSDYWKIASHSGYKDM6AFUNDC1chrX44833960chrX44386611425

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KDM6A-FUNDC1

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-B14:023BVN5492LQSDYWKIASHSGY-7.9962-8.1096
HLA-B14:023BVN5492LQSDYWKIASHSGY-5.70842-6.74372
HLA-B52:013W395492LQSDYWKIASHSGY-6.83737-6.95077
HLA-B52:013W395492LQSDYWKIASHSGY-4.4836-5.5189
HLA-A11:014UQ25492LQSDYWKIASHSGY-10.0067-10.1201
HLA-A11:014UQ25492LQSDYWKIASHSGY-9.03915-10.0745
HLA-A24:025HGA5492LQSDYWKIASHSGY-6.56204-6.67544
HLA-A24:025HGA5492LQSDYWKIASHSGY-5.42271-6.45801
HLA-B44:053DX85492LQSDYWKIASHSGY-7.85648-8.89178
HLA-B44:053DX85492LQSDYWKIASHSGY-5.3978-5.5112
HLA-A02:016TDR5492LQSDYWKIASHSGY-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of KDM6A-FUNDC1

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
KDM6A-FUNDC1chrX44833960chrX443866111020YWKIASHSGYTACTGGAAGATTGCTAGTCATAGTGGCTAT
KDM6A-FUNDC1chrX44833960chrX443866111120WKIASHSGYTGGAAGATTGCTAGTCATAGTGGCTAT
KDM6A-FUNDC1chrX44833960chrX443866111221KIASHSGYVAAGATTGCTAGTCATAGTGGCTATGTG
KDM6A-FUNDC1chrX44833960chrX44386611514SLQSDYWKIAGTTTACAGTCTGACTACTGGAAGATT
KDM6A-FUNDC1chrX44833960chrX44386611614LQSDYWKITTACAGTCTGACTACTGGAAGATT
KDM6A-FUNDC1chrX44833960chrX44386611817SDYWKIASHTCTGACTACTGGAAGATTGCTAGTCAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
KDM6A-FUNDC1chrX44833960chrX44386611520SLQSDYWKIASHSGYAGTTTACAGTCTGACTACTGGAAGATTGCTAGTCATAGTGGCTAT
KDM6A-FUNDC1chrX44833960chrX44386611621LQSDYWKIASHSGYVTTACAGTCTGACTACTGGAAGATTGCTAGTCATAGTGGCTATGTG
KDM6A-FUNDC1chrX44833960chrX44386611722QSDYWKIASHSGYVQCAGTCTGACTACTGGAAGATTGCTAGTCATAGTGGCTATGTGCAG

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Information of the samples that have these potential fusion neoantigens of KDM6A-FUNDC1

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
ACCKDM6A-FUNDC1chrX44833960ENST00000377967chrX44386611ENST00000378045TCGA-OR-A5KV

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Potential target of CAR-T therapy development for KDM6A-FUNDC1

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
TgeneFUNDC1chrX:44833960chrX:44386611ENST0000037804525134_1540156.0TransmembraneHelical

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 KDM6A-FUNDC1

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 KDM6A-FUNDC1

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