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Fusion Protein:RHBDL3-CTLA4

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: RHBDL3-CTLA4
	FusionPDB ID: 73892
	FusionGDB2.0 ID: 73892
		Hgene	Tgene
	Gene symbol	RHBDL3	CTLA4
	Gene ID	162494	1493
	Gene name	rhomboid like 3	cytotoxic T-lymphocyte associated protein 4
	Synonyms	RHBDL4\|VRHO	ALPS5\|CD\|CD152\|CELIAC3\|CTLA-4\|GRD4\|GSE\|IDDM12
	Cytomap	17q11.2	2q33.2
	Type of gene	protein-coding	protein-coding
	Description	rhomboid-related protein 3rhomboid, veinlet-like 3rhomboid, veinlet-like 4ventrhoid transmembrane protein	cytotoxic T-lymphocyte protein 4CD152 isoformceliac disease 3cytotoxic T lymphocyte associated antigen 4 short spliced formcytotoxic T-lymphocyte-associated serine esterase-4insulin-dependent diabetes mellitus 12ligand and transmembrane spliced cyto
	Modification date	20200313	20200329
	UniProtAcc	.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000269051, ENST00000536287, ENST00000538145,	ENST00000427473, ENST00000487393, ENST00000295854, ENST00000302823, ENST00000472206,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	2 X 2 X 2=8	2 X 1 X 2=4
	# samples	2	2
	** MAII score	log2(2/8*10)=1.32192809488736	log2(2/4*10)=2.32192809488736
Fusion gene context	PubMed: RHBDL3 [Title/Abstract] AND CTLA4 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: RHBDL3 [Title/Abstract] AND CTLA4 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	RHBDL3(30625223)-CTLA4(204735309), # samples:1
Anticipated loss of major functional domain due to fusion event.	RHBDL3-CTLA4 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. RHBDL3-CTLA4 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
Tgene	CTLA4	GO:0045590	negative regulation of regulatory T cell differentiation	18641304

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:30625223/chr2:204735309)
- 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 RHBDL3 (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 CTLA4 (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)
ENST00000269051	RHBDL3	chr17	30625223	+	ENST00000302823	CTLA4	chr2	204735309	+	2506	795	14	1357	447
ENST00000269051	RHBDL3	chr17	30625223	+	ENST00000295854	CTLA4	chr2	204735309	+	1211	795	14	1210	399
ENST00000269051	RHBDL3	chr17	30625223	+	ENST00000472206	CTLA4	chr2	204735309	+	963	795	14	925	303
ENST00000538145	RHBDL3	chr17	30625223	+	ENST00000302823	CTLA4	chr2	204735309	+	2481	770	13	1332	439
ENST00000538145	RHBDL3	chr17	30625223	+	ENST00000295854	CTLA4	chr2	204735309	+	1186	770	13	1185	391
ENST00000538145	RHBDL3	chr17	30625223	+	ENST00000472206	CTLA4	chr2	204735309	+	938	770	13	900	295
ENST00000536287	RHBDL3	chr17	30625223	+	ENST00000302823	CTLA4	chr2	204735309	+	2320	609	74	1171	365
ENST00000536287	RHBDL3	chr17	30625223	+	ENST00000295854	CTLA4	chr2	204735309	+	1025	609	74	1024	317
ENST00000536287	RHBDL3	chr17	30625223	+	ENST00000472206	CTLA4	chr2	204735309	+	777	609	74	739	221

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
ENST00000269051	ENST00000302823	RHBDL3	chr17	30625223	+	CTLA4	chr2	204735309	+	0.000843642	0.99915636
ENST00000269051	ENST00000295854	RHBDL3	chr17	30625223	+	CTLA4	chr2	204735309	+	0.00515747	0.9948426
ENST00000269051	ENST00000472206	RHBDL3	chr17	30625223	+	CTLA4	chr2	204735309	+	0.008682662	0.9913174
ENST00000538145	ENST00000302823	RHBDL3	chr17	30625223	+	CTLA4	chr2	204735309	+	0.001029601	0.9989704
ENST00000538145	ENST00000295854	RHBDL3	chr17	30625223	+	CTLA4	chr2	204735309	+	0.006072662	0.99392736
ENST00000538145	ENST00000472206	RHBDL3	chr17	30625223	+	CTLA4	chr2	204735309	+	0.009663314	0.99033666
ENST00000536287	ENST00000302823	RHBDL3	chr17	30625223	+	CTLA4	chr2	204735309	+	0.000876457	0.9991235
ENST00000536287	ENST00000295854	RHBDL3	chr17	30625223	+	CTLA4	chr2	204735309	+	0.003102846	0.9968971
ENST00000536287	ENST00000472206	RHBDL3	chr17	30625223	+	CTLA4	chr2	204735309	+	0.018367428	0.9816326

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 RHBDL3-CTLA4

+/-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
RHBDL3	chr17	30625223	CTLA4	chr2	204735309	609	178	TRIGLVYVAGVVAAMHVAQPAVVLAS
RHBDL3	chr17	30625223	CTLA4	chr2	204735309	770	252	TRIGLVYVAGVVAAMHVAQPAVVLAS
RHBDL3	chr17	30625223	CTLA4	chr2	204735309	795	260	TRIGLVYVAGVVAAMHVAQPAVVLAS

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Potential FusionNeoAntigen Information of RHBDL3-CTLA4 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.

RHBDL3-CTLA4_30625223_204735309.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)
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A26:02	YVAGVVAAM	0.9898	0.7898	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:08	YVAGVVAAM	0.9897	0.8272	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:02	YVAGVVAAM	0.989	0.9498	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:01	YVAGVVAAM	0.9831	0.8807	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B46:01	YVAGVVAAM	0.9805	0.5748	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A66:01	YVAGVVAAM	0.98	0.8493	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A26:15	YVAGVVAAM	0.9781	0.8439	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A26:14	YVAGVVAAM	0.9781	0.8439	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:03	YVAGVVAAM	0.9762	0.8873	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A02:21	YVAGVVAAM	0.9685	0.6994	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A26:03	YVAGVVAAM	0.9611	0.8409	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A34:05	YVAGVVAAM	0.9534	0.8561	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A34:01	YVAGVVAAM	0.9534	0.8561	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A02:04	YVAGVVAAM	0.9519	0.8032	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:05	YVAGVVAAM	0.9509	0.5932	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A02:17	YVAGVVAAM	0.9477	0.8625	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A26:08	YVAGVVAAM	0.9079	0.53	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:04	YVAGVVAAM	0.8496	0.9614	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:02	YVAGVVAAM	0.8496	0.9614	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A68:06	YVAGVVAAM	0.8435	0.6527	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A66:03	YVAGVVAAM	0.7236	0.5735	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B81:01	YVAGVVAAM	0.556	0.576	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:19	YVAGVVAAM	0.9975	0.9884	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:08	YVAGVVAAM	0.9969	0.867	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:07	YVAGVVAAM	0.9954	0.9721	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C12:12	YVAGVVAAM	0.9906	0.941	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:21	YVAGVVAAM	0.9901	0.9323	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C15:04	YVAGVVAAM	0.9867	0.9181	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C06:03	YVAGVVAAM	0.9838	0.9946	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C04:06	YVAGVVAAM	0.9838	0.9732	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C12:04	YVAGVVAAM	0.9826	0.9958	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:31	YVAGVVAAM	0.98	0.8745	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A26:01	YVAGVVAAM	0.9781	0.8439	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A02:05	YVAGVVAAM	0.9734	0.5038	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:05	YVAGVVAAM	0.9697	0.8679	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C08:13	YVAGVVAAM	0.9685	0.994	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C08:04	YVAGVVAAM	0.9685	0.994	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C08:03	YVAGVVAAM	0.9586	0.9935	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:04	YVAGVVAAM	0.9386	0.9286	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C02:06	YVAGVVAAM	0.9116	0.9726	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B56:04	YVAGVVAAM	0.8976	0.5281	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:14	YVAGVVAAM	0.8914	0.9822	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:12	YVAGVVAAM	0.8496	0.9614	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B39:10	YVAGVVAAM	0.7495	0.8357	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:04	YVAGVVAAM	0.9988	0.9852	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:03	YVAGVVAAM	0.9988	0.9852	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:02	YVAGVVAAM	0.9983	0.9736	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C12:02	YVAGVVAAM	0.9981	0.9769	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:67	YVAGVVAAM	0.9974	0.9772	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:17	YVAGVVAAM	0.9961	0.9686	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:05	YVAGVVAAM	0.9951	0.909	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C12:03	YVAGVVAAM	0.9947	0.9889	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C16:04	YVAGVVAAM	0.9931	0.9824	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:11	YVAGVVAAM	0.9914	0.9195	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:08	YVAGVVAAM	0.9913	0.9171	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:11	YVAGVVAAM	0.9907	0.9278	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:43	YVAGVVAAM	0.9898	0.9179	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C15:09	YVAGVVAAM	0.9867	0.9181	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:77	YVAGVVAAM	0.9831	0.8807	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:23	YVAGVVAAM	0.9824	0.9024	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A25:01	YVAGVVAAM	0.9823	0.914	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C03:06	YVAGVVAAM	0.9804	0.9874	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:20	YVAGVVAAM	0.9777	0.911	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:13	YVAGVVAAM	0.9738	0.8906	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:20	YVAGVVAAM	0.9714	0.9039	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A02:14	YVAGVVAAM	0.9693	0.6607	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B07:13	YVAGVVAAM	0.9692	0.7971	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A02:06	YVAGVVAAM	0.9685	0.6994	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C08:01	YVAGVVAAM	0.9586	0.9935	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:30	YVAGVVAAM	0.953	0.7648	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:17	YVAGVVAAM	0.953	0.7648	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A68:02	YVAGVVAAM	0.9499	0.6385	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A02:03	YVAGVVAAM	0.943	0.6973	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A69:01	YVAGVVAAM	0.939	0.7517	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:73	YVAGVVAAM	0.9315	0.9353	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:24	YVAGVVAAM	0.9103	0.8773	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B56:02	YVAGVVAAM	0.8976	0.5281	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B15:30	YVAGVVAAM	0.8969	0.9357	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C02:10	YVAGVVAAM	0.8603	0.9819	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C02:02	YVAGVVAAM	0.8603	0.9819	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B35:09	YVAGVVAAM	0.8496	0.9614	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A66:02	YVAGVVAAM	0.7949	0.5896	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C17:01	YVAGVVAAM	0.3994	0.9859	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-B40:21	YVAGVVAAM	0.2996	0.5312	6	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C14:02	VYVAGVVAAM	0.9373	0.9798	5	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-C14:03	VYVAGVVAAM	0.9373	0.9798	5	15
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A68:02	YVAGVVAAMHV	0.9969	0.7372	6	17
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	795	HLA-A69:01	YVAGVVAAMHV	0.994	0.7457	6	17

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Potential FusionNeoAntigen Information of RHBDL3-CTLA4 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 RHBDL3-CTLA4

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
10838	YVAGVVAAMHVAQP	RHBDL3	CTLA4	chr17	30625223	chr2	204735309	795

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RHBDL3-CTLA4

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	10838	YVAGVVAAMHVAQP	-7.9962	-8.1096
HLA-B14:02	3BVN	10838	YVAGVVAAMHVAQP	-5.70842	-6.74372
HLA-B52:01	3W39	10838	YVAGVVAAMHVAQP	-6.83737	-6.95077
HLA-B52:01	3W39	10838	YVAGVVAAMHVAQP	-4.4836	-5.5189
HLA-A11:01	4UQ2	10838	YVAGVVAAMHVAQP	-10.0067	-10.1201
HLA-A11:01	4UQ2	10838	YVAGVVAAMHVAQP	-9.03915	-10.0745
HLA-A24:02	5HGA	10838	YVAGVVAAMHVAQP	-6.56204	-6.67544
HLA-A24:02	5HGA	10838	YVAGVVAAMHVAQP	-5.42271	-6.45801
HLA-B44:05	3DX8	10838	YVAGVVAAMHVAQP	-7.85648	-8.89178
HLA-B44:05	3DX8	10838	YVAGVVAAMHVAQP	-5.3978	-5.5112
HLA-A02:01	6TDR	10838	YVAGVVAAMHVAQP	-3.37154	-4.40684

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Vaccine Design for the FusionNeoAntigens of RHBDL3-CTLA4

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
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	5	15	VYVAGVVAAM	TCTACGTGGCCGGTGTTGTGGCAGCAATGC
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	6	15	YVAGVVAAM	ACGTGGCCGGTGTTGTGGCAGCAATGC
RHBDL3-CTLA4	chr17	30625223	chr2	204735309	6	17	YVAGVVAAMHV	ACGTGGCCGGTGTTGTGGCAGCAATGCACGTGG

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 RHBDL3-CTLA4

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
GBM	RHBDL3-CTLA4	chr17	30625223	ENST00000269051	chr2	204735309	ENST00000295854	TCGA-19-A60I-01A

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Potential target of CAR-T therapy development for RHBDL3-CTLA4

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

Hgene

RHBDL3

chr17:30625223

chr2:204735309

ENST00000269051

164_184

260

405.0

Transmembrane

Helical

Hgene

RHBDL3

chr17:30625223

chr2:204735309

ENST00000269051

218_238

260

405.0

Transmembrane

Helical

Tgene

CTLA4

chr17:30625223

chr2:204735309

ENST00000295854

162_182

175.0

Transmembrane

Helical

Tgene

CTLA4

chr17:30625223

chr2:204735309

ENST00000302823

162_182

224.0

Transmembrane

Helical

Tgene

CTLA4

chr17:30625223

chr2:204735309

ENST00000427473

162_182

138.0

Transmembrane

Helical

Tgene

CTLA4

chr17:30625223

chr2:204735309

ENST00000472206

162_182

80.0

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 RHBDL3-CTLA4

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 RHBDL3-CTLA4

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)