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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:SDHC-KDM3B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SDHC-KDM3B
FusionPDB ID: 79919
FusionGDB2.0 ID: 79919
HgeneTgene
Gene symbol

SDHC

KDM3B

Gene ID

6391

51780

Gene namesuccinate dehydrogenase complex subunit Clysine demethylase 3B
SynonymsCYB560|CYBL|PGL3|QPS1|SDH35qNCA|C5orf7|JMJD1B|NET22
Cytomap

1q23.3

5q31.2

Type of geneprotein-codingprotein-coding
Descriptionsuccinate dehydrogenase cytochrome b560 subunit, mitochondrialcytochrome B large subunit of complex IIintegral membrane protein CII-3blarge subunit of cytochrome bsuccinate dehydrgenase cytochrome bsuccinate dehydrogenase 3, integral membrane subunitlysine-specific demethylase 3BjmjC domain-containing histone demethylation protein 2Bjumonji domain containing 1Bjumonji domain-containing protein 1Blysine (K)-specific demethylase 3Bnuclear protein 5qNCA
Modification date2020031320200313
UniProtAcc.

Q7LBC6

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. Demethylation of Lys residue generates formaldehyde and succinate. May have tumor suppressor activity. {ECO:0000269|PubMed:16603237}.
Ensembl transtripts involved in fusion geneENST idsENST00000342751, ENST00000367975, 
ENST00000392169, ENST00000432287, 
ENST00000513009, ENST00000470743, 
ENST00000542866, ENST00000508386, 
ENST00000314358, ENST00000394866, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 3 X 5=9011 X 11 X 5=605
# samples 613
** MAII scorelog2(6/90*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/605*10)=-2.2184235191335
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SDHC [Title/Abstract] AND KDM3B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SDHC [Title/Abstract] AND KDM3B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SDHC(161284215)-KDM3B(137733866), # samples:1
Anticipated loss of major functional domain due to fusion event.SDHC-KDM3B 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.
SDHC-KDM3B 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.
SDHC-KDM3B 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.
SDHC-KDM3B 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


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/chr1:161284215/chr5:137733866)
- 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 SDHC (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 KDM3B (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)
ENST00000367975SDHCchr1161284215+ENST00000314358KDM3Bchr5137733866+3951169562623855
ENST00000367975SDHCchr1161284215+ENST00000394866KDM3Bchr5137733866+3951169562623855
ENST00000342751SDHCchr1161284215+ENST00000314358KDM3Bchr5137733866+382745252499824
ENST00000342751SDHCchr1161284215+ENST00000394866KDM3Bchr5137733866+382745252499824
ENST00000432287SDHCchr1161284215+ENST00000314358KDM3Bchr5137733866+382644242498824
ENST00000432287SDHCchr1161284215+ENST00000394866KDM3Bchr5137733866+382644242498824
ENST00000392169SDHCchr1161284215+ENST00000314358KDM3Bchr5137733866+382038182492824
ENST00000392169SDHCchr1161284215+ENST00000394866KDM3Bchr5137733866+382038182492824
ENST00000513009SDHCchr1161284215+ENST00000314358KDM3Bchr5137733866+382038182492824
ENST00000513009SDHCchr1161284215+ENST00000394866KDM3Bchr5137733866+382038182492824

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
ENST00000367975ENST00000314358SDHCchr1161284215+KDM3Bchr5137733866+0.0007366980.99926335
ENST00000367975ENST00000394866SDHCchr1161284215+KDM3Bchr5137733866+0.0007366980.99926335
ENST00000342751ENST00000314358SDHCchr1161284215+KDM3Bchr5137733866+0.0008572850.99914265
ENST00000342751ENST00000394866SDHCchr1161284215+KDM3Bchr5137733866+0.0008572850.99914265
ENST00000432287ENST00000314358SDHCchr1161284215+KDM3Bchr5137733866+0.000856470.9991435
ENST00000432287ENST00000394866SDHCchr1161284215+KDM3Bchr5137733866+0.000856470.9991435
ENST00000392169ENST00000314358SDHCchr1161284215+KDM3Bchr5137733866+0.0008680840.999132
ENST00000392169ENST00000394866SDHCchr1161284215+KDM3Bchr5137733866+0.0008680840.999132
ENST00000513009ENST00000314358SDHCchr1161284215+KDM3Bchr5137733866+0.0008680840.999132
ENST00000513009ENST00000394866SDHCchr1161284215+KDM3Bchr5137733866+0.0008680840.999132

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 SDHC-KDM3B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SDHCchr1161284215KDM3Bchr513773386616936LPSRPEPKMAALLLRLIFTRKGVLRV

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Potential FusionNeoAntigen Information of SDHC-KDM3B 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.
SDHC-KDM3B_161284215_137733866.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)
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B51:02MAALLLRLI0.99560.6163817
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A02:13KMAALLLRL0.99070.5562716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B51:01MAALLLRLI0.9860.6468817
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A32:13KMAALLLRL0.98580.9098716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A02:04KMAALLLRL0.98540.5079716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A02:38KMAALLLRL0.98110.6017716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A74:03LLLRLIFTR0.97840.63541120
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A74:11LLLRLIFTR0.97840.63541120
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A74:09LLLRLIFTR0.97840.63541120
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A31:02LLLRLIFTR0.93620.57551120
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B08:01EPKMAALLL0.85380.5378514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B08:09EPKMAALLL0.79020.5716514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B35:03EPKMAALLL0.73410.6624514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B35:04EPKMAALLL0.47770.7279514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B35:02EPKMAALLL0.47770.7279514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B13:02KMAALLLRL0.13850.5252716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B13:01KMAALLLRL0.12640.9555716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A74:03ALLLRLIFTR0.97560.71411020
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A74:09ALLLRLIFTR0.97560.71411020
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A74:11ALLLRLIFTR0.97560.71411020
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A31:01LLLRLIFTR0.98090.55481120
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B15:04KMAALLLRL0.96590.7702716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-C06:03MAALLLRLI0.95050.9875817
SDHC-KDM3Bchr1161284215chr5137733866169HLA-C12:04MAALLLRLI0.94930.9846817
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B51:08MAALLLRLI0.94260.5699817
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B42:02EPKMAALLL0.92310.5516514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B42:01EPKMAALLL0.87650.5336514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B35:12EPKMAALLL0.47770.7279514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B39:10EPKMAALLL0.33880.7805514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B42:02RPEPKMAALLL0.97960.506314
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B39:10RPEPKMAALLL0.76980.8813314
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A32:01KMAALLLRL0.99620.9048716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A02:03KMAALLLRL0.99460.5075716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B51:21MAALLLRLI0.98880.6278817
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B51:14MAALLLRLI0.98740.6634817
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A74:01LLLRLIFTR0.97840.63541120
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B51:09MAALLLRLI0.96310.5506817
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B15:73KMAALLLRL0.8850.8822716
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B08:18EPKMAALLL0.85380.5378514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B08:12EPKMAALLL0.55460.6669514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B35:09EPKMAALLL0.47770.7279514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B67:01EPKMAALLL0.41780.6052514
SDHC-KDM3Bchr1161284215chr5137733866169HLA-A74:01ALLLRLIFTR0.97560.71411020
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B35:13RPEPKMAALLL0.88340.7709314
SDHC-KDM3Bchr1161284215chr5137733866169HLA-B67:01RPEPKMAALLL0.7710.7221314

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Potential FusionNeoAntigen Information of SDHC-KDM3B 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 SDHC-KDM3B

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
6732PKMAALLLRLIFTRSDHCKDM3Bchr1161284215chr5137733866169

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SDHC-KDM3B

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-B14:023BVN6732PKMAALLLRLIFTR-7.9962-8.1096
HLA-B14:023BVN6732PKMAALLLRLIFTR-5.70842-6.74372
HLA-B52:013W396732PKMAALLLRLIFTR-6.83737-6.95077
HLA-B52:013W396732PKMAALLLRLIFTR-4.4836-5.5189
HLA-A11:014UQ26732PKMAALLLRLIFTR-10.0067-10.1201
HLA-A11:014UQ26732PKMAALLLRLIFTR-9.03915-10.0745
HLA-A24:025HGA6732PKMAALLLRLIFTR-6.56204-6.67544
HLA-A24:025HGA6732PKMAALLLRLIFTR-5.42271-6.45801
HLA-B44:053DX86732PKMAALLLRLIFTR-7.85648-8.89178
HLA-B44:053DX86732PKMAALLLRLIFTR-5.3978-5.5112
HLA-A02:016TDR6732PKMAALLLRLIFTR-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SDHC-KDM3B

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
SDHC-KDM3Bchr1161284215chr51377338661020ALLLRLIFTRGTTGCTGAGGTTGATCTTCACTCGAAAAGG
SDHC-KDM3Bchr1161284215chr51377338661120LLLRLIFTRGCTGAGGTTGATCTTCACTCGAAAAGG
SDHC-KDM3Bchr1161284215chr5137733866314RPEPKMAALLLGGAACCCAAGATGGCTGCGCTGTTGCTGAGGTT
SDHC-KDM3Bchr1161284215chr5137733866514EPKMAALLLCAAGATGGCTGCGCTGTTGCTGAGGTT
SDHC-KDM3Bchr1161284215chr5137733866716KMAALLLRLGGCTGCGCTGTTGCTGAGGTTGATCTT
SDHC-KDM3Bchr1161284215chr5137733866817MAALLLRLITGCGCTGTTGCTGAGGTTGATCTTCAC

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 SDHC-KDM3B

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
BRCASDHC-KDM3Bchr1161284215ENST00000367975chr5137733866ENST00000314358TCGA-A2-A0YG

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Potential target of CAR-T therapy development for SDHC-KDM3B

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 SDHC-KDM3B

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 SDHC-KDM3B

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