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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:KDM3A-SUCLG2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KDM3A-SUCLG2
FusionPDB ID: 41769
FusionGDB2.0 ID: 41769
HgeneTgene
Gene symbol

KDM3A

SUCLG2

Gene ID

55818

8801

Gene namelysine demethylase 3Asuccinate-CoA ligase GDP-forming subunit beta
SynonymsJHDM2A|JHMD2A|JMJD1|JMJD1A|TSGAG-SCS|GBETA|GTPSCS
Cytomap

2p11.2

3p14.1

Type of geneprotein-codingprotein-coding
Descriptionlysine-specific demethylase 3AjmjC domain-containing histone demethylation protein 2Ajumonji C domain-containing histone demethylase 2Ajumonji domain-containing protein 1Alysine (K)-specific demethylase 3Atestis-specific protein Asuccinate--CoA ligase [GDP-forming] subunit beta, mitochondrialGTP-specific succinyl-CoA synthetase beta subunitGTP-specific succinyl-CoA synthetase subunit betaSCS-betaGsuccinate-CoA ligase GDP-forming beta subunitsuccinyl-CoA ligase [GDP-forming] s
Modification date2020031320200313
UniProtAcc

Q9Y4C1

Main function of 5'-partner protein: FUNCTION: Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue generates formaldehyde and succinate. Involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes, resulting in H3 'Lys-9' demethylation and transcriptional activation. Involved in spermatogenesis by regulating expression of target genes such as PRM1 and TNP1 which are required for packaging and condensation of sperm chromatin. Involved in obesity resistance through regulation of metabolic genes such as PPARA and UCP1. {ECO:0000269|PubMed:16603237, ECO:0000269|PubMed:28262558}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000312912, ENST00000409064, 
ENST00000409556, ENST00000542128, 
ENST00000485171, 
ENST00000307227, 
ENST00000492795, ENST00000493112, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 12 X 7=10926 X 5 X 4=120
# samples 158
** MAII scorelog2(15/1092*10)=-2.86393845042397
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/120*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KDM3A [Title/Abstract] AND SUCLG2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KDM3A [Title/Abstract] AND SUCLG2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KDM3A(86669356)-SUCLG2(67660020), # samples:2
Anticipated loss of major functional domain due to fusion event.KDM3A-SUCLG2 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.
KDM3A-SUCLG2 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.
KDM3A-SUCLG2 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.
KDM3A-SUCLG2 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
HgeneKDM3A

GO:0009755

hormone-mediated signaling pathway

16603237

HgeneKDM3A

GO:0030521

androgen receptor signaling pathway

16603237

HgeneKDM3A

GO:0033169

histone H3-K9 demethylation

16603237

HgeneKDM3A

GO:0046293

formaldehyde biosynthetic process

16603237



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/chr2:86669356/chr3:67660020)
- 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 KDM3A (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 SUCLG2 (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)
ENST00000409556KDM3Achr286669356+ENST00000493112SUCLG2chr367660020-19595513651789474
ENST00000409556KDM3Achr286669356+ENST00000307227SUCLG2chr367660020-27915513651765466
ENST00000409556KDM3Achr286669356+ENST00000492795SUCLG2chr367660020-19585513651606413
ENST00000312912KDM3Achr286669356+ENST00000493112SUCLG2chr367660020-19215133271751474
ENST00000312912KDM3Achr286669356+ENST00000307227SUCLG2chr367660020-27535133271727466
ENST00000312912KDM3Achr286669356+ENST00000492795SUCLG2chr367660020-19205133271568413
ENST00000409064KDM3Achr286669356+ENST00000493112SUCLG2chr367660020-1652244581482474
ENST00000409064KDM3Achr286669356+ENST00000307227SUCLG2chr367660020-2484244581458466
ENST00000409064KDM3Achr286669356+ENST00000492795SUCLG2chr367660020-1651244581299413
ENST00000542128KDM3Achr286669356+ENST00000493112SUCLG2chr367660020-159418601424474
ENST00000542128KDM3Achr286669356+ENST00000307227SUCLG2chr367660020-242618601400466
ENST00000542128KDM3Achr286669356+ENST00000492795SUCLG2chr367660020-159318601241413

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
ENST00000409556ENST00000493112KDM3Achr286669356+SUCLG2chr367660020-0.0007426670.99925727
ENST00000409556ENST00000307227KDM3Achr286669356+SUCLG2chr367660020-0.0001589340.9998411
ENST00000409556ENST00000492795KDM3Achr286669356+SUCLG2chr367660020-0.0007631030.99923694
ENST00000312912ENST00000493112KDM3Achr286669356+SUCLG2chr367660020-0.0004441860.99955577
ENST00000312912ENST00000307227KDM3Achr286669356+SUCLG2chr367660020-0.0001206310.99987936
ENST00000312912ENST00000492795KDM3Achr286669356+SUCLG2chr367660020-0.0004961350.99950385
ENST00000409064ENST00000493112KDM3Achr286669356+SUCLG2chr367660020-0.000405070.999595
ENST00000409064ENST00000307227KDM3Achr286669356+SUCLG2chr367660020-0.0001162230.9998838
ENST00000409064ENST00000492795KDM3Achr286669356+SUCLG2chr367660020-0.0004986890.99950135
ENST00000542128ENST00000493112KDM3Achr286669356+SUCLG2chr367660020-0.0003597580.9996402
ENST00000542128ENST00000307227KDM3Achr286669356+SUCLG2chr367660020-0.0001071210.99989283
ENST00000542128ENST00000492795KDM3Achr286669356+SUCLG2chr367660020-0.0004147680.9995852

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 KDM3A-SUCLG2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KDM3Achr286669356SUCLG2chr36766002018660IRAVSHTDVTKKDLKAVQLTSRRWLN
KDM3Achr286669356SUCLG2chr36766002024460IRAVSHTDVTKKDLKAVQLTSRRWLN
KDM3Achr286669356SUCLG2chr36766002051360IRAVSHTDVTKKDLKAVQLTSRRWLN
KDM3Achr286669356SUCLG2chr36766002055160IRAVSHTDVTKKDLKAVQLTSRRWLN

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Potential FusionNeoAntigen Information of KDM3A-SUCLG2 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.
KDM3A-SUCLG2_86669356_67660020.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)
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:24KKDLKAVQL0.98750.78411019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:01KKDLKAVQL0.96660.96111019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:13KKDLKAVQL0.93910.97641019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B38:02KKDLKAVQL0.9090.98561019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B48:01KKDLKAVQL0.63010.78561019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B07:10KKDLKAVQL0.01830.60691019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:01SHTDVTKKDL0.98320.6195414
KDM3A-SUCLG2chr286669356chr367660020513HLA-A33:05DLKAVQLTSR0.98240.72271222
KDM3A-SUCLG2chr286669356chr367660020513HLA-A33:01DLKAVQLTSR0.98240.72271222
KDM3A-SUCLG2chr286669356chr367660020513HLA-B38:01SHTDVTKKDL0.96190.7547414
KDM3A-SUCLG2chr286669356chr367660020513HLA-B38:02SHTDVTKKDL0.960.7488414
KDM3A-SUCLG2chr286669356chr367660020513HLA-A33:01DLKAVQLTSRR0.99340.80541223
KDM3A-SUCLG2chr286669356chr367660020513HLA-A33:05DLKAVQLTSRR0.99340.80541223
KDM3A-SUCLG2chr286669356chr367660020513HLA-C05:09HTDVTKKDL0.99980.9015514
KDM3A-SUCLG2chr286669356chr367660020513HLA-C08:15HTDVTKKDL0.99960.963514
KDM3A-SUCLG2chr286669356chr367660020513HLA-C04:10KKDLKAVQL0.99220.931019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C04:07KKDLKAVQL0.98850.91841019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:09KKDLKAVQL0.97840.85311019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:12KKDLKAVQL0.9770.96471019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C07:29KKDLKAVQL0.92770.96631019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C07:13KKDLKAVQL0.91740.95781019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:05KKDLKAVQL0.86380.95441019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C08:04HTDVTKKDL0.78360.8972514
KDM3A-SUCLG2chr286669356chr367660020513HLA-C08:13HTDVTKKDL0.78360.8972514
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:08KKDLKAVQL0.61150.87361019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B14:03KKDLKAVQL0.54250.85151019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C04:14KKDLKAVQL0.43880.94241019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C08:03HTDVTKKDL0.40810.955514
KDM3A-SUCLG2chr286669356chr367660020513HLA-B48:03KKDLKAVQL0.32980.62611019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:05SHTDVTKKDL0.96930.6063414
KDM3A-SUCLG2chr286669356chr367660020513HLA-A33:03DLKAVQLTSR0.88210.72191222
KDM3A-SUCLG2chr286669356chr367660020513HLA-A33:03DLKAVQLTSRR0.96390.8261223
KDM3A-SUCLG2chr286669356chr367660020513HLA-C05:01HTDVTKKDL0.99980.9015514
KDM3A-SUCLG2chr286669356chr367660020513HLA-C04:03HTDVTKKDL0.99970.7166514
KDM3A-SUCLG2chr286669356chr367660020513HLA-C08:02HTDVTKKDL0.99960.963514
KDM3A-SUCLG2chr286669356chr367660020513HLA-C18:01KKDLKAVQL0.99480.91351019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C04:01KKDLKAVQL0.98850.91841019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:02KKDLKAVQL0.98220.97431019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:31KKDLKAVQL0.96970.96211019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C06:06KKDLKAVQL0.79720.99421019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C07:04KKDLKAVQL0.66150.9811019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:11KKDLKAVQL0.63570.85321019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B15:09KKDLKAVQL0.42240.81181019
KDM3A-SUCLG2chr286669356chr367660020513HLA-C08:01HTDVTKKDL0.40810.955514
KDM3A-SUCLG2chr286669356chr367660020513HLA-B40:12KKDLKAVQL0.32980.62611019
KDM3A-SUCLG2chr286669356chr367660020513HLA-B07:13HTDVTKKDL0.0050.5217514
KDM3A-SUCLG2chr286669356chr367660020513HLA-B38:05SHTDVTKKDL0.96190.7547414
KDM3A-SUCLG2chr286669356chr367660020513HLA-B39:11SHTDVTKKDL0.85410.5909414

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Potential FusionNeoAntigen Information of KDM3A-SUCLG2 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 KDM3A-SUCLG2

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
9289TDVTKKDLKAVQLTKDM3ASUCLG2chr286669356chr367660020513

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KDM3A-SUCLG2

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-B14:023BVN9289TDVTKKDLKAVQLT-7.9962-8.1096
HLA-B14:023BVN9289TDVTKKDLKAVQLT-5.70842-6.74372
HLA-B52:013W399289TDVTKKDLKAVQLT-6.83737-6.95077
HLA-B52:013W399289TDVTKKDLKAVQLT-4.4836-5.5189
HLA-A11:014UQ29289TDVTKKDLKAVQLT-10.0067-10.1201
HLA-A11:014UQ29289TDVTKKDLKAVQLT-9.03915-10.0745
HLA-A24:025HGA9289TDVTKKDLKAVQLT-6.56204-6.67544
HLA-A24:025HGA9289TDVTKKDLKAVQLT-5.42271-6.45801
HLA-B44:053DX89289TDVTKKDLKAVQLT-7.85648-8.89178
HLA-B44:053DX89289TDVTKKDLKAVQLT-5.3978-5.5112
HLA-A02:016TDR9289TDVTKKDLKAVQLT-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of KDM3A-SUCLG2

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
KDM3A-SUCLG2chr286669356chr3676600201019KKDLKAVQLGATCTGAAGGCAGTTCAATTAACCTCC
KDM3A-SUCLG2chr286669356chr3676600201222DLKAVQLTSRAAGGCAGTTCAATTAACCTCCAGAAGATGG
KDM3A-SUCLG2chr286669356chr3676600201223DLKAVQLTSRRAAGGCAGTTCAATTAACCTCCAGAAGATGGCTG
KDM3A-SUCLG2chr286669356chr367660020414SHTDVTKKDLACCGACGTTACCAAGAAGGATCTGAAGGCA
KDM3A-SUCLG2chr286669356chr367660020514HTDVTKKDLGACGTTACCAAGAAGGATCTGAAGGCA

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 KDM3A-SUCLG2

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
OVKDM3A-SUCLG2chr286669356ENST00000312912chr367660020ENST00000307227TCGA-23-1122-01A

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Potential target of CAR-T therapy development for KDM3A-SUCLG2

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 KDM3A-SUCLG2

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 KDM3A-SUCLG2

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