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Fusion Protein:RYR2-MTR |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: RYR2-MTR | FusionPDB ID: 78806 | FusionGDB2.0 ID: 78806 | Hgene | Tgene | Gene symbol | RYR2 | MTR | Gene ID | 6262 | 4548 |
| Gene name | ryanodine receptor 2 | 5-methyltetrahydrofolate-homocysteine methyltransferase | |
| Synonyms | ARVC2|ARVD2|RYR-2|RyR|VTSIP | HMAG|MS|cblG | |
| Cytomap | 1q43 | 1q43 | |
| Type of gene | protein-coding | protein-coding | |
| Description | ryanodine receptor 2cardiac muscle ryanodine receptor-calcium release channelcardiac-type ryanodine receptorislet-type ryanodine receptorkidney-type ryanodine receptorryanodine receptor 2 (cardiac)type 2 ryanodine receptor | methionine synthase5-methyltetrahydrofolate-homocysteine methyltransferase 1cobalamin-dependent methionine synthasevitamin-B12 dependent methionine synthase | |
| Modification date | 20200315 | 20200313 | |
| UniProtAcc | . | Q9UBK8 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000360064, ENST00000366574, ENST00000542537, ENST00000609119, | ENST00000418145, ENST00000470570, ENST00000535889, ENST00000366577, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 10 X 11 X 5=550 | 5 X 5 X 2=50 |
| # samples | 11 | 5 | |
| ** MAII score | log2(11/550*10)=-2.32192809488736 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(5/50*10)=0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: RYR2 [Title/Abstract] AND MTR [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | RYR2(237551483)-MTR(237044055), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | RYR2-MTR 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. RYR2-MTR 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. RYR2-MTR 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. RYR2-MTR 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 | RYR2 | GO:0005513 | detection of calcium ion | 10830164 |
| Hgene | RYR2 | GO:0006816 | calcium ion transport | 17921453 |
| Hgene | RYR2 | GO:0031000 | response to caffeine | 17921453 |
| Hgene | RYR2 | GO:0035584 | calcium-mediated signaling using intracellular calcium source | 17921453 |
| Hgene | RYR2 | GO:0051209 | release of sequestered calcium ion into cytosol | 12443530|17921453 |
| Hgene | RYR2 | GO:0051284 | positive regulation of sequestering of calcium ion | 12443530|12919952 |
| Hgene | RYR2 | GO:0051775 | response to redox state | 19226252 |
| Hgene | RYR2 | GO:0060402 | calcium ion transport into cytosol | 17921453 |
| Hgene | RYR2 | GO:0071313 | cellular response to caffeine | 12919952 |
| Hgene | RYR2 | GO:0072599 | establishment of protein localization to endoplasmic reticulum | 12443530 |
| Hgene | RYR2 | GO:1901896 | positive regulation of calcium-transporting ATPase activity | 12443530 |
| Fusion gene breakpoints across RYR2 (5'-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 gene breakpoints across MTR (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 Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0) * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | Non-Cancer | ERR315413 | RYR2 | chr1 | 237551483 | + | MTR | chr1 | 237044055 | + |
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Fusion ORF Analysis |
| 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) |
| ENST00000366574 | RYR2 | chr1 | 237551483 | + | ENST00000366577 | MTR | chr1 | 237044055 | + | 8631 | 1090 | 35 | 2293 | 752 |
| ENST00000360064 | RYR2 | chr1 | 237551483 | + | ENST00000366577 | MTR | chr1 | 237044055 | + | 8308 | 767 | 0 | 1970 | 656 |
| ENST00000542537 | RYR2 | chr1 | 237551483 | + | ENST00000366577 | MTR | chr1 | 237044055 | + | 8266 | 725 | 15 | 1928 | 637 |
| 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 |
| ENST00000366574 | ENST00000366577 | RYR2 | chr1 | 237551483 | + | MTR | chr1 | 237044055 | + | 0.000564066 | 0.99943596 |
| ENST00000360064 | ENST00000366577 | RYR2 | chr1 | 237551483 | + | MTR | chr1 | 237044055 | + | 0.001317921 | 0.9986821 |
| ENST00000542537 | ENST00000366577 | RYR2 | chr1 | 237551483 | + | MTR | chr1 | 237044055 | + | 0.000549984 | 0.99945 |
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Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >78806_78806_1_RYR2-MTR_RYR2_chr1_237551483_ENST00000360064_MTR_chr1_237044055_ENST00000366577_length(amino acids)=656AA_BP=255 LGPRSSSNKLSNKKMMKWFCSAPQPSTKNNRSYAWQQKDLATDFVSWSPLPIPRMCPQTSPSAPLCWSSPSLSGRCRRCWLTPWRNQKGQ LDIIKWSFGLKTAQGGGHRTLLYGHAILLRHSYSGMYLCCLSTSRSSTDKLAFDVGLQEDTTGEACWWTIHPASKQRSEGEKVRVGDDLI LVSVSSERYLHLSYGNGSLHVDAAFQQTLWSVAPISSGSEAAQGYLIGGDVLRLLHGHMDECLTVPSGEHGEEQRRTHTAVKIAPRYSAP VIHVLDASKSVVVCSQLLDENLKDEYFEEIMEEYEDIRQDHYESLKERRYLPLSQARKSGFQMDWLSEPHPVKPTFIGTQVFEDYDLQKL VDYIDWKPFFDVWQLRGKYPNRGFPKIFNDKTVGGEARKVYDDAHNMLNTLISQKKLRARGVVGFWPAQSIQDDIHLYAEAAVPQAAEPI ATFYGLRQQAEKDSASTEPYYCLSDFIAPLHSGIRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEELHERVRREL WAYCGSEQLDVADLRRLRYKGIRPAPGYPSQPDHTEKLTMWRLADIEQSTGIRLTESLAMAPASAVSGLYFSNLKSKYFAVGKISKDQVE -------------------------------------------------------------- >78806_78806_2_RYR2-MTR_RYR2_chr1_237551483_ENST00000366574_MTR_chr1_237044055_ENST00000366577_length(amino acids)=752AA_BP=351 MGCGAASPRPPGPGRPPPAQCGAGRPRASTTRARASAPPPPLCRRGPPGARHPAARPPPAPGSRQQKQKAAPGAAAAAELRGAREPAPAR RRGTMADGGEGEDEIQFLRTDDEVVLQCTATIHKEQQKLCLAAEGFGNRLCFLESTSNSKNVPPDLSICTFVLEQSLSVRALQEMLANTV EKSEGQVDVEKWKFMMKTAQGGGHRTLLYGHAILLRHSYSGMYLCCLSTSRSSTDKLAFDVGLQEDTTGEACWWTIHPASKQRSEGEKVR VGDDLILVSVSSERYLHLSYGNGSLHVDAAFQQTLWSVAPISSGSEAAQGYLIGGDVLRLLHGHMDECLTVPSGEHGEEQRRTHTAVKIA PRYSAPVIHVLDASKSVVVCSQLLDENLKDEYFEEIMEEYEDIRQDHYESLKERRYLPLSQARKSGFQMDWLSEPHPVKPTFIGTQVFED YDLQKLVDYIDWKPFFDVWQLRGKYPNRGFPKIFNDKTVGGEARKVYDDAHNMLNTLISQKKLRARGVVGFWPAQSIQDDIHLYAEAAVP QAAEPIATFYGLRQQAEKDSASTEPYYCLSDFIAPLHSGIRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEELHE RVRRELWAYCGSEQLDVADLRRLRYKGIRPAPGYPSQPDHTEKLTMWRLADIEQSTGIRLTESLAMAPASAVSGLYFSNLKSKYFAVGKI -------------------------------------------------------------- >78806_78806_3_RYR2-MTR_RYR2_chr1_237551483_ENST00000542537_MTR_chr1_237044055_ENST00000366577_length(amino acids)=637AA_BP=236 MQCTATIHKEQQKLCLAAEGFGNRLCFLESTSNSKNVPPDLSICTFVLEQSLSVRALQEMLANTVEKSEGQVDVEKWKFMMKTAQGGGHR TLLYGHAILLRHSYSGMYLCCLSTSRSSTDKLAFDVGLQEDTTGEACWWTIHPASKQRSEGEKVRVGDDLILVSVSSERYLHLSYGNGSL HVDAAFQQTLWSVAPISSGSEAAQGYLIGGDVLRLLHGHMDECLTVPSGEHGEEQRRTHTAVKIAPRYSAPVIHVLDASKSVVVCSQLLD ENLKDEYFEEIMEEYEDIRQDHYESLKERRYLPLSQARKSGFQMDWLSEPHPVKPTFIGTQVFEDYDLQKLVDYIDWKPFFDVWQLRGKY PNRGFPKIFNDKTVGGEARKVYDDAHNMLNTLISQKKLRARGVVGFWPAQSIQDDIHLYAEAAVPQAAEPIATFYGLRQQAEKDSASTEP YYCLSDFIAPLHSGIRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEELHERVRRELWAYCGSEQLDVADLRRLRY KGIRPAPGYPSQPDHTEKLTMWRLADIEQSTGIRLTESLAMAPASAVSGLYFSNLKSKYFAVGKISKDQVEDYALRKNISVAEVEKWLGP -------------------------------------------------------------- |
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Fusion Protein Functional Features |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:237551483/chr1:237044055) - 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. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| . | MTR |
| FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes. | FUNCTION: Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin (PubMed:17892308). Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to the inactive cob(II)alamin species (Probable). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:27771510). Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (By similarity). Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme (PubMed:16769880). Also serves as an aquacob(III)alamin reductase by reducing aquacob(III)alamin to cob(II)alamin; this reduction leads to stimulation of the conversion of apoMTR and aquacob(III)alamin to MTR holoenzyme (PubMed:16769880). {ECO:0000250|UniProtKB:Q8C1A3, ECO:0000269|PubMed:16769880, ECO:0000269|PubMed:17892308, ECO:0000269|PubMed:27771510, ECO:0000305|PubMed:19243433}. |
| 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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 110_165 | 257.6666666666667 | 4968.0 | Domain | MIR 1 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 172_217 | 257.6666666666667 | 4968.0 | Domain | MIR 2 |
| Tgene | MTR | chr1:237551483 | chr1:237044055 | ENST00000366577 | 23 | 33 | 923_1265 | 864.6666666666666 | 1266.0 | Domain | AdoMet activation | |
| Tgene | MTR | chr1:237551483 | chr1:237044055 | ENST00000366577 | 23 | 33 | 1227_1228 | 864.6666666666666 | 1266.0 | Region | S-adenosyl-L-methionine binding |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4412_4445 | 257.6666666666667 | 4968.0 | Coiled coil | Ontology_term=ECO:0000255 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4414_4455 | 257.6666666666667 | 4968.0 | Compositional bias | Note=Glu-rich (acidic) |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 1025_1222 | 257.6666666666667 | 4968.0 | Domain | B30.2/SPRY 2 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 1337_1562 | 257.6666666666667 | 4968.0 | Domain | B30.2/SPRY 3 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 225_280 | 257.6666666666667 | 4968.0 | Domain | MIR 3 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 286_343 | 257.6666666666667 | 4968.0 | Domain | MIR 4 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 351_408 | 257.6666666666667 | 4968.0 | Domain | MIR 5 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 599_809 | 257.6666666666667 | 4968.0 | Domain | B30.2/SPRY 1 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4820_4829 | 257.6666666666667 | 4968.0 | Intramembrane | Pore-forming |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 853_2925 | 257.6666666666667 | 4968.0 | Region | Note=4 X approximate repeats |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 2692_2810 | 257.6666666666667 | 4968.0 | Repeat | Note=3 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 2812_2925 | 257.6666666666667 | 4968.0 | Repeat | Note=4 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 853_966 | 257.6666666666667 | 4968.0 | Repeat | Note=1 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 967_1080 | 257.6666666666667 | 4968.0 | Repeat | Note=2 |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 1_4281 | 257.6666666666667 | 4968.0 | Topological domain | Cytoplasmic |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4871_4967 | 257.6666666666667 | 4968.0 | Topological domain | Cytoplasmic |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4282_4302 | 257.6666666666667 | 4968.0 | Transmembrane | Helical |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4504_4524 | 257.6666666666667 | 4968.0 | Transmembrane | Helical |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4580_4600 | 257.6666666666667 | 4968.0 | Transmembrane | Helical |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4730_4750 | 257.6666666666667 | 4968.0 | Transmembrane | Helical |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4769_4789 | 257.6666666666667 | 4968.0 | Transmembrane | Helical |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 4850_4870 | 257.6666666666667 | 4968.0 | Transmembrane | Helical |
| Tgene | MTR | chr1:237551483 | chr1:237044055 | ENST00000366577 | 23 | 33 | 19_338 | 864.6666666666666 | 1266.0 | Domain | Hcy-binding | |
| Tgene | MTR | chr1:237551483 | chr1:237044055 | ENST00000366577 | 23 | 33 | 371_632 | 864.6666666666666 | 1266.0 | Domain | Pterin-binding | |
| Tgene | MTR | chr1:237551483 | chr1:237044055 | ENST00000366577 | 23 | 33 | 662_759 | 864.6666666666666 | 1266.0 | Domain | B12-binding N-terminal | |
| Tgene | MTR | chr1:237551483 | chr1:237044055 | ENST00000366577 | 23 | 33 | 772_907 | 864.6666666666666 | 1266.0 | Domain | B12-binding | |
| Tgene | MTR | chr1:237551483 | chr1:237044055 | ENST00000366577 | 23 | 33 | 382_384 | 864.6666666666666 | 1266.0 | Region | Substrate binding | |
| Tgene | MTR | chr1:237551483 | chr1:237044055 | ENST00000366577 | 23 | 33 | 782_786 | 864.6666666666666 | 1266.0 | Region | Methylcob(III)alamin binding |
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Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| RYR2 | |
| MTR |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| Hgene | RYR2 | chr1:237551483 | chr1:237044055 | ENST00000366574 | + | 10 | 105 | 3581_3610 | 257.6666666666667 | 4968.0 | CALM |
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Related Drugs to RYR2-MTR |
| 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 RYR2-MTR |
| 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 |
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