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Fusion Protein:MSH2-TTC7A

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: MSH2-TTC7A
	FusionPDB ID: 55278
	FusionGDB2.0 ID: 55278
		Hgene	Tgene
	Gene symbol	MSH2	TTC7A
	Gene ID	4436	57217
	Gene name	mutS homolog 2	tetratricopeptide repeat domain 7A
	Synonyms	COCA1\|FCC1\|HNPCC\|HNPCC1\|LCFS2\|hMSH2	GIDID\|MINAT\|TTC7
	Cytomap	2p21-p16.3	2p21
	Type of gene	protein-coding	protein-coding
	Description	DNA mismatch repair protein Msh2DNA mismatch repair protein Msh2 transcriptmutS homolog 2, colon cancer, nonpolyposis type 1	tetratricopeptide repeat protein 7ATPR repeat protein 7A
	Modification date	20200322	20200320
	UniProtAcc	P43246 Main function of 5'-partner protein: FUNCTION: Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containing DNA strand (PubMed:26300262). ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis. {ECO:0000269\|PubMed:10078208, ECO:0000269\|PubMed:10660545, ECO:0000269\|PubMed:15064730, ECO:0000269\|PubMed:17611581, ECO:0000269\|PubMed:21120944, ECO:0000269\|PubMed:26300262, ECO:0000269\|PubMed:9564049, ECO:0000269\|PubMed:9822679, ECO:0000269\|PubMed:9822680}.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000233146, ENST00000406134, ENST00000543555, ENST00000461394,	ENST00000263737, ENST00000394850, ENST00000461601, ENST00000536057, ENST00000319190, ENST00000409245,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	15 X 12 X 10=1800	12 X 13 X 9=1404
	# samples	23	15
	** MAII score	log2(23/1800*10)=-2.96829114027266 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(15/1404*10)=-3.22650852980868 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: MSH2 [Title/Abstract] AND TTC7A [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: MSH2 [Title/Abstract] AND TTC7A [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	MSH2(47641557)-TTC7A(47233061), # samples:2
Anticipated loss of major functional domain due to fusion event.	MSH2-TTC7A 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. MSH2-TTC7A 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. MSH2-TTC7A seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. MSH2-TTC7A seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. MSH2-TTC7A seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.

* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

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	MSH2	GO:0006281	DNA repair	8942985
Hgene	MSH2	GO:0006298	mismatch repair	7923193\|11555625
Hgene	MSH2	GO:0006301	postreplication repair	7923193
Hgene	MSH2	GO:0045910	negative regulation of DNA recombination	17715146
Hgene	MSH2	GO:0051096	positive regulation of helicase activity	17715146
Tgene	TTC7A	GO:0072659	protein localization to plasma membrane	23229899

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr2:47641557/chr2:47233061)
- 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 MSH2 (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 TTC7A (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)
ENST00000233146	MSH2	chr2	47641557	+	ENST00000409245	TTC7A	chr2	47233060	+	2802	1165	223	2676	817
ENST00000233146	MSH2	chr2	47641557	+	ENST00000319190	TTC7A	chr2	47233060	+	4889	1165	223	2676	817
ENST00000543555	MSH2	chr2	47641557	+	ENST00000409245	TTC7A	chr2	47233060	+	2520	883	7	2394	795
ENST00000543555	MSH2	chr2	47641557	+	ENST00000319190	TTC7A	chr2	47233060	+	4607	883	7	2394	795
ENST00000406134	MSH2	chr2	47641557	+	ENST00000409245	TTC7A	chr2	47233060	+	2641	1004	62	2515	817
ENST00000406134	MSH2	chr2	47641557	+	ENST00000319190	TTC7A	chr2	47233060	+	4728	1004	62	2515	817
ENST00000233146	MSH2	chr2	47641557	+	ENST00000409245	TTC7A	chr2	47233061	+	2802	1165	223	2676	817
ENST00000233146	MSH2	chr2	47641557	+	ENST00000319190	TTC7A	chr2	47233061	+	4889	1165	223	2676	817
ENST00000543555	MSH2	chr2	47641557	+	ENST00000409245	TTC7A	chr2	47233061	+	2520	883	7	2394	795
ENST00000543555	MSH2	chr2	47641557	+	ENST00000319190	TTC7A	chr2	47233061	+	4607	883	7	2394	795
ENST00000406134	MSH2	chr2	47641557	+	ENST00000409245	TTC7A	chr2	47233061	+	2641	1004	62	2515	817
ENST00000406134	MSH2	chr2	47641557	+	ENST00000319190	TTC7A	chr2	47233061	+	4728	1004	62	2515	817
ENST00000233146	MSH2	chr2	47630541	-	ENST00000409245	TTC7A	chr2	47177502	+	2952	434	223	2826	867
ENST00000233146	MSH2	chr2	47630541	-	ENST00000319190	TTC7A	chr2	47177502	+	5039	434	223	2826	867
ENST00000543555	MSH2	chr2	47630541	-	ENST00000409245	TTC7A	chr2	47177502	+	2670	152	7	2544	845
ENST00000543555	MSH2	chr2	47630541	-	ENST00000319190	TTC7A	chr2	47177502	+	4757	152	7	2544	845
ENST00000406134	MSH2	chr2	47630541	-	ENST00000409245	TTC7A	chr2	47177502	+	2791	273	62	2665	867
ENST00000406134	MSH2	chr2	47630541	-	ENST00000319190	TTC7A	chr2	47177502	+	4878	273	62	2665	867

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
ENST00000233146	ENST00000409245	MSH2	chr2	47641557	+	TTC7A	chr2	47233060	+	0.010405251	0.9895948
ENST00000233146	ENST00000319190	MSH2	chr2	47641557	+	TTC7A	chr2	47233060	+	0.005793156	0.9942068
ENST00000543555	ENST00000409245	MSH2	chr2	47641557	+	TTC7A	chr2	47233060	+	0.01093755	0.9890625
ENST00000543555	ENST00000319190	MSH2	chr2	47641557	+	TTC7A	chr2	47233060	+	0.006448325	0.9935516
ENST00000406134	ENST00000409245	MSH2	chr2	47641557	+	TTC7A	chr2	47233060	+	0.010998234	0.98900175
ENST00000406134	ENST00000319190	MSH2	chr2	47641557	+	TTC7A	chr2	47233060	+	0.005949792	0.9940502
ENST00000233146	ENST00000409245	MSH2	chr2	47641557	+	TTC7A	chr2	47233061	+	0.010405251	0.9895948
ENST00000233146	ENST00000319190	MSH2	chr2	47641557	+	TTC7A	chr2	47233061	+	0.005793156	0.9942068
ENST00000543555	ENST00000409245	MSH2	chr2	47641557	+	TTC7A	chr2	47233061	+	0.01093755	0.9890625
ENST00000543555	ENST00000319190	MSH2	chr2	47641557	+	TTC7A	chr2	47233061	+	0.006448325	0.9935516
ENST00000406134	ENST00000409245	MSH2	chr2	47641557	+	TTC7A	chr2	47233061	+	0.010998234	0.98900175
ENST00000406134	ENST00000319190	MSH2	chr2	47641557	+	TTC7A	chr2	47233061	+	0.005949792	0.9940502
ENST00000233146	ENST00000409245	MSH2	chr2	47630541	-	TTC7A	chr2	47177502	+	0.009955966	0.990044
ENST00000233146	ENST00000319190	MSH2	chr2	47630541	-	TTC7A	chr2	47177502	+	0.004743867	0.9952561
ENST00000543555	ENST00000409245	MSH2	chr2	47630541	-	TTC7A	chr2	47177502	+	0.012284842	0.9877152
ENST00000543555	ENST00000319190	MSH2	chr2	47630541	-	TTC7A	chr2	47177502	+	0.005795005	0.99420506
ENST00000406134	ENST00000409245	MSH2	chr2	47630541	-	TTC7A	chr2	47177502	+	0.010785677	0.98921436
ENST00000406134	ENST00000319190	MSH2	chr2	47630541	-	TTC7A	chr2	47177502	+	0.004948411	0.99505156

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 MSH2-TTC7A

+/-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
MSH2	chr2	47630541	TTC7A	chr2	47177502	152	48	FKTQGVIKYMGPADDFGKLLLAEALL
MSH2	chr2	47630541	TTC7A	chr2	47177502	273	70	FKTQGVIKYMGPADDFGKLLLAEALL
MSH2	chr2	47630541	TTC7A	chr2	47177502	434	70	FKTQGVIKYMGPADDFGKLLLAEALL
MSH2	chr2	47641557	TTC7A	chr2	47233060	1004	276	QVAVSSLSAVIKFLELLSDDSNFGQF
MSH2	chr2	47641557	TTC7A	chr2	47233060	1165	276	QVAVSSLSAVIKFLELLSDDSNFGQF
MSH2	chr2	47641557	TTC7A	chr2	47233060	883	254	QVAVSSLSAVIKFLELLSDDSNFGQF
MSH2	chr2	47641557	TTC7A	chr2	47233061	1004	276	QVAVSSLSAVIKFLELLSDDSNFGQF
MSH2	chr2	47641557	TTC7A	chr2	47233061	1165	276	QVAVSSLSAVIKFLELLSDDSNFGQF
MSH2	chr2	47641557	TTC7A	chr2	47233061	883	254	QVAVSSLSAVIKFLELLSDDSNFGQF

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Potential FusionNeoAntigen Information of MSH2-TTC7A 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.

MSH2-TTC7A_47630541_47177502.msa
MSH2-TTC7A_47641557_47233060.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)
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:03	GPADDFGKL	0.8276	0.7864	10	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:04	GPADDFGKL	0.5434	0.8987	10	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:02	GPADDFGKL	0.5434	0.8987	10	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:03	MGPADDFGKL	0.8448	0.9226	9	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:02	MGPADDFGKL	0.6601	0.9635	9	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:04	MGPADDFGKL	0.6601	0.9635	9	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B07:05	GPADDFGKLLL	0.9996	0.5071	10	21
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:03	YMGPADDFGKL	0.9835	0.8606	8	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B81:01	GPADDFGKLLL	0.9749	0.5642	10	21
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:02	YMGPADDFGKL	0.9537	0.9315	8	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:04	YMGPADDFGKL	0.9537	0.9315	8	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:15	ADDFGKLL	1	0.9375	12	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C05:09	PADDFGKLL	0.9998	0.8959	11	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C04:10	PADDFGKLL	0.9997	0.7531	11	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:15	PADDFGKLL	0.9995	0.9503	11	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B07:12	GPADDFGKL	0.8486	0.6085	10	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B39:08	ADDFGKLLL	0.5566	0.8819	12	21
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:12	GPADDFGKL	0.5434	0.8987	10	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C07:67	KYMGPADDF	0.3728	0.9441	7	16
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C07:80	KYMGPADDF	0.3728	0.9441	7	16
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C07:10	KYMGPADDF	0.352	0.9608	7	16
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:03	PADDFGKLL	0.2474	0.9575	11	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B39:10	GPADDFGKL	0.2233	0.795	10	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C05:09	GPADDFGKLL	0.9962	0.9089	10	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:15	GPADDFGKLL	0.9849	0.9604	10	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:12	MGPADDFGKL	0.6601	0.9635	9	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B39:10	MGPADDFGKL	0.5034	0.9066	9	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C05:09	MGPADDFGKLL	1	0.957	9	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:15	MGPADDFGKLL	0.9998	0.9592	9	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B07:12	GPADDFGKLLL	0.9997	0.6729	10	21
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:12	YMGPADDFGKL	0.9537	0.9315	8	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B39:10	YMGPADDFGKL	0.8808	0.9392	8	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:02	ADDFGKLL	1	0.9375	12	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C04:03	PADDFGKLL	0.9998	0.821	11	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C05:01	PADDFGKLL	0.9998	0.8959	11	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:02	PADDFGKLL	0.9995	0.9503	11	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:13	GPADDFGKL	0.7876	0.7971	10	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:09	GPADDFGKL	0.5434	0.8987	10	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C07:02	KYMGPADDF	0.3728	0.9441	7	16
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B67:01	GPADDFGKL	0.2494	0.5963	10	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:01	PADDFGKLL	0.2474	0.9575	11	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C14:03	KYMGPADDF	0.0078	0.9341	7	16
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C14:02	KYMGPADDF	0.0078	0.9341	7	16
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C05:01	GPADDFGKLL	0.9962	0.9089	10	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:02	GPADDFGKLL	0.9849	0.9604	10	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:09	MGPADDFGKL	0.6601	0.9635	9	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B67:01	MGPADDFGKL	0.516	0.8461	9	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C05:01	MGPADDFGKLL	1	0.957	9	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-C08:02	MGPADDFGKLL	0.9998	0.9592	9	20
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B67:01	GPADDFGKLLL	0.9573	0.7412	10	21
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B35:09	YMGPADDFGKL	0.9537	0.9315	8	19
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	HLA-B67:01	YMGPADDFGKL	0.9099	0.8972	8	19
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B14:02	SAVIKFLEL	0.996	0.8306	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B14:01	SAVIKFLEL	0.996	0.8306	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B08:01	SAVIKFLEL	0.9955	0.7047	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B08:09	SAVIKFLEL	0.9894	0.7218	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:13	SLSAVIKFL	0.9892	0.5918	5	14
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:11	SLSAVIKFL	0.9876	0.5073	5	14
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:22	AVIKFLELL	0.9851	0.5697	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:21	AVIKFLELL	0.9802	0.6683	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:04	AVIKFLELL	0.9792	0.7167	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:17	AVIKFLELL	0.9789	0.6146	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:20	AVIKFLELL	0.9776	0.55	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B52:01	SAVIKFLEL	0.9718	0.8445	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:35	SLSAVIKFL	0.969	0.5255	5	14
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B13:01	AVIKFLELL	0.3824	0.9325	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B13:01	SLSAVIKFL	0.0815	0.8692	5	14
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:07	SAVIKFLEL	0.9999	0.9792	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:08	SAVIKFLEL	0.9998	0.9169	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:19	SAVIKFLEL	0.9998	0.9919	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C15:04	SAVIKFLEL	0.9998	0.905	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C15:06	SAVIKFLEL	0.9998	0.9331	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C04:06	SAVIKFLEL	0.9994	0.9487	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C08:04	SAVIKFLEL	0.9989	0.9824	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C08:13	SAVIKFLEL	0.9989	0.9824	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C12:12	SAVIKFLEL	0.9989	0.9636	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C06:03	SAVIKFLEL	0.9987	0.9974	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C12:04	SAVIKFLEL	0.9987	0.9977	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C12:16	SAVIKFLEL	0.9986	0.9794	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B42:02	SAVIKFLEL	0.9982	0.705	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:14	SAVIKFLEL	0.9969	0.9863	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C07:13	SAVIKFLEL	0.992	0.9664	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C08:03	SAVIKFLEL	0.9917	0.9941	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C02:06	SAVIKFLEL	0.9901	0.9684	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:07	SLSAVIKFL	0.9866	0.5365	5	14
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C07:29	SAVIKFLEL	0.9858	0.9666	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:07	AVIKFLELL	0.9798	0.5747	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B51:07	SAVIKFLEL	0.9683	0.8075	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C01:30	SAVIKFLEL	0.9494	0.9747	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C01:17	SAVIKFLEL	0.9265	0.9702	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C02:06	AVIKFLELL	0.9234	0.9687	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B39:10	SAVIKFLEL	0.8889	0.9798	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B14:03	SAVIKFLEL	0.8743	0.9352	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:03	SAVIKFLEL	0.9998	0.9918	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C15:02	SAVIKFLEL	0.9998	0.9038	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:04	SAVIKFLEL	0.9998	0.9918	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C15:09	SAVIKFLEL	0.9998	0.905	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:05	SAVIKFLEL	0.9998	0.9397	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C15:05	SAVIKFLEL	0.9998	0.9505	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:67	SAVIKFLEL	0.9997	0.9854	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:17	SAVIKFLEL	0.9997	0.9764	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C16:04	SAVIKFLEL	0.9996	0.9895	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:02	SAVIKFLEL	0.9995	0.9717	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C12:03	SAVIKFLEL	0.9992	0.99	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C07:04	SAVIKFLEL	0.9989	0.9784	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C12:02	SAVIKFLEL	0.9984	0.9821	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C03:06	SAVIKFLEL	0.9981	0.9922	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C16:02	SAVIKFLEL	0.9971	0.9968	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C16:01	SAVIKFLEL	0.9965	0.9891	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:03	SLSAVIKFL	0.9963	0.5877	5	14
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B08:18	SAVIKFLEL	0.9955	0.7047	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B35:13	SAVIKFLEL	0.9942	0.947	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C08:01	SAVIKFLEL	0.9917	0.9941	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C02:10	SAVIKFLEL	0.988	0.9816	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C02:02	SAVIKFLEL	0.988	0.9816	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B08:12	SAVIKFLEL	0.9863	0.8736	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C06:08	SAVIKFLEL	0.9854	0.9937	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:14	AVIKFLELL	0.9806	0.5908	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A02:06	AVIKFLELL	0.9802	0.6683	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A32:01	AVIKFLELL	0.9721	0.9833	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-A69:01	AVIKFLELL	0.971	0.7161	8	17
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C01:03	SAVIKFLEL	0.9403	0.9731	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C17:01	SAVIKFLEL	0.9391	0.8657	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C01:02	SAVIKFLEL	0.934	0.969	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-B07:13	SAVIKFLEL	0.8639	0.8488	7	16
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	HLA-C17:01	SLSAVIKFL	0.3815	0.5385	5	14

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Potential FusionNeoAntigen Information of MSH2-TTC7A in HLA II

MSH2-TTC7A_47630541_47177502.msa
MSH2-TTC7A_47641557_47233060.msa

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)
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-0411	QGVIKYMGPADDFGK	3	18
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-0411	TQGVIKYMGPADDFG	2	17
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-0467	QGVIKYMGPADDFGK	3	18
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-0467	TQGVIKYMGPADDFG	2	17
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-0480	QGVIKYMGPADDFGK	3	18
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-0491	QGVIKYMGPADDFGK	3	18
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-0491	TQGVIKYMGPADDFG	2	17
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-1002	QGVIKYMGPADDFGK	3	18
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-1002	TQGVIKYMGPADDFG	2	17
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-1512	TQGVIKYMGPADDFG	2	17
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-1512	KTQGVIKYMGPADDF	1	16
MSH2-TTC7A	chr2	47630541	chr2	47177502	434	DRB1-1512	FKTQGVIKYMGPADD	0	15
MSH2-TTC7A	chr2	47641557	chr2	47233060	1165	DRB1-0422	KFLELLSDDSNFGQF	11	26

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Fusion breakpoint peptide structures of MSH2-TTC7A

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
3774	IKYMGPADDFGKLL	MSH2	TTC7A	chr2	47630541	chr2	47177502	434

File name	BPseq	Hgene	Tgene	Hchr	Hbp	Tchr	Tbp	AAlen
5588	LSAVIKFLELLSDD	MSH2	TTC7A	chr2	47641557	chr2	47233060	1165

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MSH2-TTC7A

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	3774	IKYMGPADDFGKLL	-7.9962	-8.1096
HLA-B14:02	3BVN	3774	IKYMGPADDFGKLL	-5.70842	-6.74372
HLA-B52:01	3W39	3774	IKYMGPADDFGKLL	-6.83737	-6.95077
HLA-B52:01	3W39	3774	IKYMGPADDFGKLL	-4.4836	-5.5189
HLA-A11:01	4UQ2	3774	IKYMGPADDFGKLL	-10.0067	-10.1201
HLA-A11:01	4UQ2	3774	IKYMGPADDFGKLL	-9.03915	-10.0745
HLA-A24:02	5HGA	3774	IKYMGPADDFGKLL	-6.56204	-6.67544
HLA-A24:02	5HGA	3774	IKYMGPADDFGKLL	-5.42271	-6.45801
HLA-B44:05	3DX8	3774	IKYMGPADDFGKLL	-7.85648	-8.89178
HLA-B44:05	3DX8	3774	IKYMGPADDFGKLL	-5.3978	-5.5112
HLA-A02:01	6TDR	3774	IKYMGPADDFGKLL	-3.37154	-4.40684
HLA-B14:02	3BVN	5588	LSAVIKFLELLSDD	-6.77781	-6.89121
HLA-B14:02	3BVN	5588	LSAVIKFLELLSDD	-3.08719	-4.12249
HLA-B52:01	3W39	5588	LSAVIKFLELLSDD	-6.66315	-6.77655
HLA-B52:01	3W39	5588	LSAVIKFLELLSDD	-2.65785	-3.69315
HLA-A24:02	5HGA	5588	LSAVIKFLELLSDD	-7.20627	-7.31967
HLA-A24:02	5HGA	5588	LSAVIKFLELLSDD	-6.50211	-7.53741
HLA-B44:05	3DX8	5588	LSAVIKFLELLSDD	-7.75024	-7.86364
HLA-B44:05	3DX8	5588	LSAVIKFLELLSDD	-6.53073	-7.56603
HLA-A02:01	6TDR	5588	LSAVIKFLELLSDD	-4.4528	-5.4881

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Vaccine Design for the FusionNeoAntigens of MSH2-TTC7A

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
MSH2-TTC7A	chr2	47630541	chr2	47177502	10	19	GPADDFGKL	GGCCGGCAGATGACTTTGGGAAATTGC
MSH2-TTC7A	chr2	47630541	chr2	47177502	10	20	GPADDFGKLL	GGCCGGCAGATGACTTTGGGAAATTGCTGC
MSH2-TTC7A	chr2	47630541	chr2	47177502	10	21	GPADDFGKLLL	GGCCGGCAGATGACTTTGGGAAATTGCTGCTGG
MSH2-TTC7A	chr2	47630541	chr2	47177502	11	20	PADDFGKLL	CGGCAGATGACTTTGGGAAATTGCTGC
MSH2-TTC7A	chr2	47630541	chr2	47177502	12	20	ADDFGKLL	CAGATGACTTTGGGAAATTGCTGC
MSH2-TTC7A	chr2	47630541	chr2	47177502	12	21	ADDFGKLLL	CAGATGACTTTGGGAAATTGCTGCTGG
MSH2-TTC7A	chr2	47630541	chr2	47177502	7	16	KYMGPADDF	AGTACATGGGGCCGGCAGATGACTTTG
MSH2-TTC7A	chr2	47630541	chr2	47177502	8	19	YMGPADDFGKL	ACATGGGGCCGGCAGATGACTTTGGGAAATTGC
MSH2-TTC7A	chr2	47630541	chr2	47177502	9	19	MGPADDFGKL	TGGGGCCGGCAGATGACTTTGGGAAATTGC
MSH2-TTC7A	chr2	47630541	chr2	47177502	9	20	MGPADDFGKLL	TGGGGCCGGCAGATGACTTTGGGAAATTGCTGC
MSH2-TTC7A	chr2	47641557	chr2	47233060	5	14	SLSAVIKFL	GTCAGAGCCCTTAACCTTTTTCAGGCA
MSH2-TTC7A	chr2	47641557	chr2	47233060	7	16	SAVIKFLEL	GCCCTTAACCTTTTTCAGGCAACTCGA
MSH2-TTC7A	chr2	47641557	chr2	47233060	8	17	AVIKFLELL	CTTAACCTTTTTCAGGCAACTCGAGAT

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
MSH2-TTC7A	chr2	47630541	chr2	47177502	0	15	FKTQGVIKYMGPADD	TCAAGACCCAGGGGGTGATCAAGTACATGGGGCCGGCAGATGACT
MSH2-TTC7A	chr2	47630541	chr2	47177502	1	16	KTQGVIKYMGPADDF	AGACCCAGGGGGTGATCAAGTACATGGGGCCGGCAGATGACTTTG
MSH2-TTC7A	chr2	47630541	chr2	47177502	2	17	TQGVIKYMGPADDFG	CCCAGGGGGTGATCAAGTACATGGGGCCGGCAGATGACTTTGGGA
MSH2-TTC7A	chr2	47630541	chr2	47177502	3	18	QGVIKYMGPADDFGK	AGGGGGTGATCAAGTACATGGGGCCGGCAGATGACTTTGGGAAAT
MSH2-TTC7A	chr2	47641557	chr2	47233060	11	26	KFLELLSDDSNFGQF	TTTCAGGCAACTCGAGATGTGGTGCTGAGCCGGGTGCCGGAGCAG

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Information of the samples that have these potential fusion neoantigens of MSH2-TTC7A

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
BRCA	MSH2-TTC7A	chr2	47641557	ENST00000233146	chr2	47233060	ENST00000319190	TCGA-A7-A26G
PRAD	MSH2-TTC7A	chr2	47630541	ENST00000233146	chr2	47177502	ENST00000319190	TCGA-KK-A5A1-01A

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Potential target of CAR-T therapy development for MSH2-TTC7A

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

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 MSH2-TTC7A

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 MSH2-TTC7A

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)