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Fusion Protein:KDM1A-EPHB2

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: KDM1A-EPHB2
	FusionPDB ID: 41698
	FusionGDB2.0 ID: 41698
		Hgene	Tgene
	Gene symbol	KDM1A	EPHB2
	Gene ID	23028	2048
	Gene name	lysine demethylase 1A	EPH receptor B2
	Synonyms	AOF2\|BHC110\|CPRF\|KDM1\|LSD1	BDPLT22\|CAPB\|DRT\|EK5\|EPHT3\|ERK\|Hek5\|PCBC\|Tyro5
	Cytomap	1p36.12	1p36.12
	Type of gene	protein-coding	protein-coding
	Description	lysine-specific histone demethylase 1ABRAF35-HDAC complex protein BHC110FAD-binding protein BRAF35-HDAC complex, 110 kDa subunitamine oxidase (flavin containing) domain 2flavin-containing amine oxidase domain-containing protein 2lysine (K)-specific d	ephrin type-B receptor 2EPH-like kinase 5developmentally-regulated Eph-related tyrosine kinaseelk-related tyrosine kinaseeph tyrosine kinase 3protein-tyrosine kinase HEK5renal carcinoma antigen NY-REN-47tyrosine-protein kinase TYRO5tyrosine-protei
	Modification date	20200329	20200313
	UniProtAcc	O60341 Main function of 5'-partner protein: FUNCTION: Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:15811342, PubMed:16140033, PubMed:16079794, PubMed:16079795, PubMed:16223729). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity (PubMed:16140033, PubMed:16079794, PubMed:16885027, PubMed:21300290, PubMed:23721412). Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A (PubMed:16079795). Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281). {ECO:0000269\|PubMed:12032298, ECO:0000269\|PubMed:15620353, ECO:0000269\|PubMed:15811342, ECO:0000269\|PubMed:16079794, ECO:0000269\|PubMed:16079795, ECO:0000269\|PubMed:16140033, ECO:0000269\|PubMed:16223729, ECO:0000269\|PubMed:16885027, ECO:0000269\|PubMed:16956976, ECO:0000269\|PubMed:17805299, ECO:0000269\|PubMed:20228790, ECO:0000269\|PubMed:20389281, ECO:0000269\|PubMed:20562920, ECO:0000269\|PubMed:21300290, ECO:0000269\|PubMed:23721412}.	P29323 Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (PubMed:30213874). {ECO:0000269\|PubMed:15300251, ECO:0000269\|PubMed:30213874}.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000356634, ENST00000400181, ENST00000542151,	ENST00000465676, ENST00000374627, ENST00000374630, ENST00000374632, ENST00000400191, ENST00000544305,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	6 X 7 X 2=84	10 X 10 X 5=500
	# samples	9	11
	** MAII score	log2(9/84*10)=0.0995356735509144 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0	log2(11/500*10)=-2.18442457113743 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: KDM1A [Title/Abstract] AND EPHB2 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: KDM1A [Title/Abstract] AND EPHB2 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	KDM1A(23357127)-EPHB2(23208851), # samples:1 KDM1A(23357127)-EPHB2(23208852), # samples:1
Anticipated loss of major functional domain due to fusion event.	KDM1A-EPHB2 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. KDM1A-EPHB2 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. KDM1A-EPHB2 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. KDM1A-EPHB2 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)

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	KDM1A	GO:0033169	histone H3-K9 demethylation	16079795\|20228790
Hgene	KDM1A	GO:0034644	cellular response to UV	24217620
Hgene	KDM1A	GO:0034720	histone H3-K4 demethylation	15620353\|20228790\|24217620
Hgene	KDM1A	GO:0043433	negative regulation of DNA-binding transcription factor activity	19497860
Hgene	KDM1A	GO:0045892	negative regulation of transcription, DNA-templated	19497860
Hgene	KDM1A	GO:0045944	positive regulation of transcription by RNA polymerase II	20833138
Hgene	KDM1A	GO:0051091	positive regulation of DNA-binding transcription factor activity	20833138

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:23357127/chr1:23208851)
- 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.

Retention 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.

Fusion gene breakpoints across KDM1A (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across EPHB2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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Fusion Amino Acid Sequences

Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	Seq length (transcript)	BP loci (transcript)	Predicted start (transcript)	Predicted stop (transcript)	Seq length (amino acids)
ENST00000356634	KDM1A	chr1	23357127	+	ENST00000544305	EPHB2	chr1	23208851	+	928	666	149	811	220
ENST00000356634	KDM1A	chr1	23357127	+	ENST00000374630	EPHB2	chr1	23208851	+	2497	666	149	2323	724
ENST00000356634	KDM1A	chr1	23357127	+	ENST00000400191	EPHB2	chr1	23208851	+	3986	666	149	2530	793
ENST00000356634	KDM1A	chr1	23357127	+	ENST00000374632	EPHB2	chr1	23208851	+	3027	666	149	2326	725
ENST00000356634	KDM1A	chr1	23357127	+	ENST00000374627	EPHB2	chr1	23208851	+	3371	666	149	2221	690
ENST00000400181	KDM1A	chr1	23357127	+	ENST00000544305	EPHB2	chr1	23208851	+	883	621	104	766	220
ENST00000400181	KDM1A	chr1	23357127	+	ENST00000374630	EPHB2	chr1	23208851	+	2452	621	104	2278	724
ENST00000400181	KDM1A	chr1	23357127	+	ENST00000400191	EPHB2	chr1	23208851	+	3941	621	104	2485	793
ENST00000400181	KDM1A	chr1	23357127	+	ENST00000374632	EPHB2	chr1	23208851	+	2982	621	104	2281	725
ENST00000400181	KDM1A	chr1	23357127	+	ENST00000374627	EPHB2	chr1	23208851	+	3326	621	104	2176	690
ENST00000542151	KDM1A	chr1	23357127	+	ENST00000544305	EPHB2	chr1	23208851	+	881	619	102	764	220
ENST00000542151	KDM1A	chr1	23357127	+	ENST00000374630	EPHB2	chr1	23208851	+	2450	619	102	2276	724
ENST00000542151	KDM1A	chr1	23357127	+	ENST00000400191	EPHB2	chr1	23208851	+	3939	619	102	2483	793
ENST00000542151	KDM1A	chr1	23357127	+	ENST00000374632	EPHB2	chr1	23208851	+	2980	619	102	2279	725
ENST00000542151	KDM1A	chr1	23357127	+	ENST00000374627	EPHB2	chr1	23208851	+	3324	619	102	2174	690
ENST00000356634	KDM1A	chr1	23357127	-	ENST00000544305	EPHB2	chr1	23208852	+	928	666	149	811	220
ENST00000356634	KDM1A	chr1	23357127	-	ENST00000374630	EPHB2	chr1	23208852	+	2497	666	149	2323	724
ENST00000356634	KDM1A	chr1	23357127	-	ENST00000400191	EPHB2	chr1	23208852	+	3986	666	149	2530	793
ENST00000356634	KDM1A	chr1	23357127	-	ENST00000374632	EPHB2	chr1	23208852	+	3027	666	149	2326	725
ENST00000356634	KDM1A	chr1	23357127	-	ENST00000374627	EPHB2	chr1	23208852	+	3371	666	149	2221	690
ENST00000400181	KDM1A	chr1	23357127	-	ENST00000544305	EPHB2	chr1	23208852	+	883	621	104	766	220
ENST00000400181	KDM1A	chr1	23357127	-	ENST00000374630	EPHB2	chr1	23208852	+	2452	621	104	2278	724
ENST00000400181	KDM1A	chr1	23357127	-	ENST00000400191	EPHB2	chr1	23208852	+	3941	621	104	2485	793
ENST00000400181	KDM1A	chr1	23357127	-	ENST00000374632	EPHB2	chr1	23208852	+	2982	621	104	2281	725
ENST00000400181	KDM1A	chr1	23357127	-	ENST00000374627	EPHB2	chr1	23208852	+	3326	621	104	2176	690
ENST00000542151	KDM1A	chr1	23357127	-	ENST00000544305	EPHB2	chr1	23208852	+	881	619	102	764	220
ENST00000542151	KDM1A	chr1	23357127	-	ENST00000374630	EPHB2	chr1	23208852	+	2450	619	102	2276	724
ENST00000542151	KDM1A	chr1	23357127	-	ENST00000400191	EPHB2	chr1	23208852	+	3939	619	102	2483	793
ENST00000542151	KDM1A	chr1	23357127	-	ENST00000374632	EPHB2	chr1	23208852	+	2980	619	102	2279	725
ENST00000542151	KDM1A	chr1	23357127	-	ENST00000374627	EPHB2	chr1	23208852	+	3324	619	102	2174	690

DeepORF 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.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	No-coding score	Coding score
ENST00000356634	ENST00000544305	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.004926997	0.995073
ENST00000356634	ENST00000374630	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.006558819	0.9934411
ENST00000356634	ENST00000400191	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.001820675	0.9981793
ENST00000356634	ENST00000374632	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.004777174	0.99522287
ENST00000356634	ENST00000374627	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.005683788	0.99431616
ENST00000400181	ENST00000544305	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.004378739	0.99562126
ENST00000400181	ENST00000374630	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.006665471	0.99333453
ENST00000400181	ENST00000400191	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.001968963	0.9980311
ENST00000400181	ENST00000374632	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.005228939	0.99477106
ENST00000400181	ENST00000374627	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.006062916	0.993937
ENST00000542151	ENST00000544305	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.004519617	0.9954804
ENST00000542151	ENST00000374630	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.006643544	0.9933564
ENST00000542151	ENST00000400191	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.001968222	0.9980318
ENST00000542151	ENST00000374632	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.00522511	0.9947748
ENST00000542151	ENST00000374627	KDM1A	chr1	23357127	+	EPHB2	chr1	23208851	+	0.006058384	0.99394166
ENST00000356634	ENST00000544305	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.004926997	0.995073
ENST00000356634	ENST00000374630	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.006558819	0.9934411
ENST00000356634	ENST00000400191	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.001820675	0.9981793
ENST00000356634	ENST00000374632	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.004777174	0.99522287
ENST00000356634	ENST00000374627	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.005683788	0.99431616
ENST00000400181	ENST00000544305	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.004378739	0.99562126
ENST00000400181	ENST00000374630	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.006665471	0.99333453
ENST00000400181	ENST00000400191	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.001968963	0.9980311
ENST00000400181	ENST00000374632	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.005228939	0.99477106
ENST00000400181	ENST00000374627	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.006062916	0.993937
ENST00000542151	ENST00000544305	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.004519617	0.9954804
ENST00000542151	ENST00000374630	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.006643544	0.9933564
ENST00000542151	ENST00000400191	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.001968222	0.9980318
ENST00000542151	ENST00000374632	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.00522511	0.9947748
ENST00000542151	ENST00000374627	KDM1A	chr1	23357127	-	EPHB2	chr1	23208852	+	0.006058384	0.99394166

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 KDM1A-EPHB2

+/-13 AA sequence from the breakpoints of the fusion protein sequences.

Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Length(fusion protein)	BP in fusion protein	Peptide
KDM1A	chr1	23357127	EPHB2	chr1	23208851	619	172	PEEENESEPEEPSAPSAVSIMHQVSR
KDM1A	chr1	23357127	EPHB2	chr1	23208851	621	172	PEEENESEPEEPSAPSAVSIMHQVSR
KDM1A	chr1	23357127	EPHB2	chr1	23208851	666	172	PEEENESEPEEPSAPSAVSIMHQVSR
KDM1A	chr1	23357127	EPHB2	chr1	23208852	619	172	PEEENESEPEEPSAPSAVSIMHQVSR
KDM1A	chr1	23357127	EPHB2	chr1	23208852	621	172	PEEENESEPEEPSAPSAVSIMHQVSR
KDM1A	chr1	23357127	EPHB2	chr1	23208852	666	172	PEEENESEPEEPSAPSAVSIMHQVSR

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Potential FusionNeoAntigen Information of KDM1A-EPHB2 in HLA I

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.

KDM1A-EPHB2_23357127_23208851.msa

Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)

Fusion gene	Hchr	Hbp	Tgene	Tchr	Tbp	HLA I	FusionNeoAntigen peptide	Binding score	Immunogenic score	Neoantigen start (at BP 13)	Neoantigen end (at BP 13)
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:02	EEPSAPSA	0.9993	0.6576	9	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B41:01	SEPEEPSA	0.9835	0.9367	6	14
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B45:01	SEPEEPSAP	0.9814	0.8533	6	15
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:02	SEPEEPSAP	0.9603	0.651	6	15
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B45:01	PEEPSAPSA	0.9393	0.9136	8	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:02	PEEPSAPSA	0.8353	0.6658	8	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B41:01	SEPEEPSAP	0.4013	0.9109	6	15
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:01	SEPEEPSAP	0.4001	0.7772	6	15
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B45:01	NESEPEEPSA	0.9897	0.7835	4	14
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B45:01	EPEEPSAPSA	0.8633	0.8893	7	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:02	EPEEPSAPSA	0.86	0.6702	7	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B41:01	NESEPEEPSA	0.7426	0.8714	4	14
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B45:01	SEPEEPSAPSA	0.9991	0.9066	6	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B41:01	SEPEEPSAPSA	0.9985	0.9279	6	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:01	SEPEEPSAPSA	0.9983	0.8113	6	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:02	SEPEEPSAPSA	0.9979	0.6945	6	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B45:01	NESEPEEPSAP	0.9969	0.784	4	15
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B35:03	EPSAPSAVSIM	0.9849	0.8271	10	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B35:04	EPSAPSAVSIM	0.9615	0.8949	10	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B35:02	EPSAPSAVSIM	0.9615	0.8949	10	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C01:30	SAPSAVSI	0.9982	0.9697	12	20
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C01:17	SAPSAVSI	0.9926	0.9573	12	20
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B78:01	EPSAPSAV	0.9909	0.6298	10	18
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B39:10	EPSAPSAV	0.5723	0.9557	10	18
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:08	SAPSAVSIM	0.9977	0.9013	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:19	SAPSAVSIM	0.9969	0.9859	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:07	SAPSAVSIM	0.99	0.9856	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C12:12	SAPSAVSIM	0.9705	0.9281	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C04:06	SAPSAVSIM	0.9614	0.9302	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C08:04	SAPSAVSIM	0.9335	0.9772	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C08:13	SAPSAVSIM	0.9335	0.9772	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C12:04	SAPSAVSIM	0.9329	0.996	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C06:03	SAPSAVSIM	0.9294	0.994	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C02:06	SAPSAVSIM	0.9269	0.9728	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C01:30	SAPSAVSIM	0.8465	0.9722	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C08:03	SAPSAVSIM	0.7943	0.9888	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C01:17	SAPSAVSIM	0.7458	0.9673	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C07:29	SAPSAVSIM	0.6528	0.9501	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B39:10	EPSAPSAVSI	0.6288	0.9324	10	20
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B40:06	SEPEEPSAPSA	0.9993	0.7141	6	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B35:12	EPSAPSAVSIM	0.9615	0.8949	10	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C01:02	SAPSAVSI	0.9937	0.9564	12	20
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C01:03	SAPSAVSI	0.9905	0.9134	12	20
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B51:29	EPSAPSAV	0.977	0.5659	10	18
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:03	SAPSAVSIM	0.9979	0.9901	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:04	SAPSAVSIM	0.9979	0.9901	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:02	SAPSAVSIM	0.997	0.9808	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:67	SAPSAVSIM	0.997	0.9824	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:05	SAPSAVSIM	0.9962	0.9428	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:17	SAPSAVSIM	0.996	0.9813	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C12:02	SAPSAVSIM	0.9787	0.9749	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C12:03	SAPSAVSIM	0.9721	0.9847	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C16:04	SAPSAVSIM	0.9662	0.9811	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C03:06	SAPSAVSIM	0.9621	0.9918	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B07:13	SAPSAVSIM	0.9252	0.8588	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C02:02	SAPSAVSIM	0.8781	0.985	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C02:10	SAPSAVSIM	0.8781	0.985	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C16:01	SAPSAVSIM	0.8731	0.9842	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C08:01	SAPSAVSIM	0.7943	0.9888	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C01:02	SAPSAVSIM	0.7342	0.9668	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-C01:03	SAPSAVSIM	0.7181	0.9462	12	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:05	SEPEEPSAP	0.4001	0.7772	6	15
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:04	SEPEEPSAP	0.4001	0.7772	6	15
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B18:08	EEPSAPSAV	0.2127	0.8919	9	18
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B67:01	EPSAPSAVSI	0.6468	0.7334	10	20
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:05	SEPEEPSAPSA	0.9983	0.8113	6	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B50:04	SEPEEPSAPSA	0.9983	0.8113	6	17
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B51:05	EPEEPSAPSAV	0.9793	0.508	7	18
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B35:09	EPSAPSAVSIM	0.9615	0.8949	10	21
KDM1A-EPHB2	chr1	23357127	chr1	23208851	666	HLA-B67:01	EPSAPSAVSIM	0.8844	0.7702	10	21

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Potential FusionNeoAntigen Information of KDM1A-EPHB2 in HLA II

Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA II

FusionNeoAntigen peptide

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of KDM1A-EPHB2

3D 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 name	BPseq	Hgene	Tgene	Hchr	Hbp	Tchr	Tbp	AAlen
8526	SEPEEPSAPSAVSI	KDM1A	EPHB2	chr1	23357127	chr1	23208851	666

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KDM1A-EPHB2

Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.

HLA allele	PDB ID	File name	BPseq	Docking score	Glide score
HLA-B14:02	3BVN	8526	SEPEEPSAPSAVSI	-7.15543	-7.26883
HLA-B14:02	3BVN	8526	SEPEEPSAPSAVSI	-4.77435	-5.80965
HLA-B52:01	3W39	8526	SEPEEPSAPSAVSI	-6.80875	-6.92215
HLA-B52:01	3W39	8526	SEPEEPSAPSAVSI	-4.20386	-5.23916
HLA-A11:01	4UQ2	8526	SEPEEPSAPSAVSI	-7.5194	-8.5547
HLA-A11:01	4UQ2	8526	SEPEEPSAPSAVSI	-6.9601	-7.0735
HLA-A24:02	5HGA	8526	SEPEEPSAPSAVSI	-7.52403	-7.63743
HLA-A24:02	5HGA	8526	SEPEEPSAPSAVSI	-5.82433	-6.85963
HLA-B27:05	6PYJ	8526	SEPEEPSAPSAVSI	-3.28285	-4.31815
HLA-B44:05	3DX8	8526	SEPEEPSAPSAVSI	-5.91172	-6.94702
HLA-B44:05	3DX8	8526	SEPEEPSAPSAVSI	-4.24346	-4.35686

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Vaccine Design for the FusionNeoAntigens of KDM1A-EPHB2

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.

Fusion gene	Hchr	Hbp	Tchr	Tbp	Start in +/-13AA	End in +/-13AA	FusionNeoAntigen peptide sequence	FusionNeoAntigen RNA sequence
KDM1A-EPHB2	chr1	23357127	chr1	23208851	10	18	EPSAPSAV	AACCATCGGCTCCATCGGCAGTGT
KDM1A-EPHB2	chr1	23357127	chr1	23208851	10	20	EPSAPSAVSI	AACCATCGGCTCCATCGGCAGTGTCCATCA
KDM1A-EPHB2	chr1	23357127	chr1	23208851	10	21	EPSAPSAVSIM	AACCATCGGCTCCATCGGCAGTGTCCATCATGC
KDM1A-EPHB2	chr1	23357127	chr1	23208851	12	20	SAPSAVSI	CGGCTCCATCGGCAGTGTCCATCA
KDM1A-EPHB2	chr1	23357127	chr1	23208851	12	21	SAPSAVSIM	CGGCTCCATCGGCAGTGTCCATCATGC
KDM1A-EPHB2	chr1	23357127	chr1	23208851	4	14	NESEPEEPSA	ATGAAAGTGAGCCTGAAGAACCATCGGCTC
KDM1A-EPHB2	chr1	23357127	chr1	23208851	4	15	NESEPEEPSAP	ATGAAAGTGAGCCTGAAGAACCATCGGCTCCAT
KDM1A-EPHB2	chr1	23357127	chr1	23208851	6	14	SEPEEPSA	GTGAGCCTGAAGAACCATCGGCTC
KDM1A-EPHB2	chr1	23357127	chr1	23208851	6	15	SEPEEPSAP	GTGAGCCTGAAGAACCATCGGCTCCAT
KDM1A-EPHB2	chr1	23357127	chr1	23208851	6	17	SEPEEPSAPSA	GTGAGCCTGAAGAACCATCGGCTCCATCGGCAG
KDM1A-EPHB2	chr1	23357127	chr1	23208851	7	17	EPEEPSAPSA	AGCCTGAAGAACCATCGGCTCCATCGGCAG
KDM1A-EPHB2	chr1	23357127	chr1	23208851	7	18	EPEEPSAPSAV	AGCCTGAAGAACCATCGGCTCCATCGGCAGTGT
KDM1A-EPHB2	chr1	23357127	chr1	23208851	8	17	PEEPSAPSA	CTGAAGAACCATCGGCTCCATCGGCAG
KDM1A-EPHB2	chr1	23357127	chr1	23208851	9	17	EEPSAPSA	AAGAACCATCGGCTCCATCGGCAG
KDM1A-EPHB2	chr1	23357127	chr1	23208851	9	18	EEPSAPSAV	AAGAACCATCGGCTCCATCGGCAGTGT

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide

FusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of KDM1A-EPHB2

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 type	Fusion gene	Hchr	Hbp	Henst	Tchr	Tbp	Tenst	Sample
STAD	KDM1A-EPHB2	chr1	23357127	ENST00000356634	chr1	23208851	ENST00000374627	TCGA-BR-4357

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Potential target of CAR-T therapy development for KDM1A-EPHB2

Predicted 3D structure. We used RoseTTAFold.

Retention 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'.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

EPHB2

chr1:23357127

chr1:23208851

ENST00000374630

544_564

987.0

Transmembrane

Helical

Tgene

EPHB2

chr1:23357127

chr1:23208851

ENST00000374632

544_564

988.0

Transmembrane

Helical

Tgene

EPHB2

chr1:23357127

chr1:23208851

ENST00000400191

544_564

1056.0

Transmembrane

Helical

Tgene

EPHB2

chr1:23357127

chr1:23208852

ENST00000374630

544_564

987.0

Transmembrane

Helical

Tgene

EPHB2

chr1:23357127

chr1:23208852

ENST00000374632

544_564

988.0

Transmembrane

Helical

Tgene

EPHB2

chr1:23357127

chr1:23208852

ENST00000400191

544_564

1056.0

Transmembrane

Helical

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.

Hgene

Hchr

Hbp

Henst

Tgene

Tchr

Tbp

Tenst

DeepLoc result

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Related Drugs to KDM1A-EPHB2

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

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Related Diseases to KDM1A-EPHB2

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source

	Fusion Gene and Fusion Protein Summary
	Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)
	Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)
	Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)
	Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)
	Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)
	Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)
	Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)
	Potential target of CAR-T therapy development
	Information on the samples that have these potential fusion neoantigens
	Fusion Protein Targeting Drugs - (Manual Curation)
	Fusion Protein Related diseases - (Manual Curation)