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Fusion Gene Summary | |
Fusion Gene ORF analysis | |
Fusion Genomic Features | |
Fusion Protein Features | |
Fusion Gene Sequence | |
Fusion Gene PPI analysis | |
Related Drugs | |
Related Diseases |
Fusion gene:DHRS1-METTL3 (FusionGDB2 ID:22547) |
Fusion Gene Summary for DHRS1-METTL3 |
Fusion gene summary |
Fusion gene information | Fusion gene name: DHRS1-METTL3 | Fusion gene ID: 22547 | Hgene | Tgene | Gene symbol | DHRS1 | METTL3 | Gene ID | 115817 | 56339 |
Gene name | dehydrogenase/reductase 1 | methyltransferase like 3 | |
Synonyms | SDR19C1 | IME4|M6A|MT-A70|Spo8|hMETTL3 | |
Cytomap | 14q12 | 14q11.2 | |
Type of gene | protein-coding | protein-coding | |
Description | dehydrogenase/reductase SDR family member 1dehydrogenase/reductase (SDR family) member 1short chain dehydrogenase/reductase family 19C member 1 | N6-adenosine-methyltransferase catalytic subunitN6-adenosine-methyltransferase 70 kDa subunitadoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferasemRNA (2'-O-methyladenosine-N(6)-)-methyltransferasemRNA m(6)A methyltransferasemethy | |
Modification date | 20200313 | 20200322 | |
UniProtAcc | Q96LJ7 | Q86U44 | |
Ensembl transtripts involved in fusion gene | ENST00000559088, ENST00000288111, ENST00000396813, | ENST00000298717, ENST00000538267, ENST00000545319, | |
Fusion gene scores | * DoF score | 3 X 3 X 3=27 | 7 X 5 X 7=245 |
# samples | 3 | 7 | |
** MAII score | log2(3/27*10)=0.15200309344505 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | log2(7/245*10)=-1.8073549220576 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
Context | PubMed: DHRS1 [Title/Abstract] AND METTL3 [Title/Abstract] AND fusion [Title/Abstract] | ||
Most frequent breakpoint | DHRS1(24768163)-METTL3(21970045), # samples:3 | ||
Anticipated loss of major functional domain due to fusion event. | DHRS1-METTL3 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 |
Tgene | METTL3 | GO:0006974 | cellular response to DNA damage stimulus | 28297716 |
Tgene | METTL3 | GO:0009048 | dosage compensation by inactivation of X chromosome | 27602518 |
Tgene | METTL3 | GO:0031053 | primary miRNA processing | 25799998 |
Tgene | METTL3 | GO:0034644 | cellular response to UV | 28297716 |
Tgene | METTL3 | GO:0080009 | mRNA methylation | 24316715|27281194|27373337|27627798|28297716 |
Tgene | METTL3 | GO:1990744 | primary miRNA methylation | 25799998 |
Fusion gene breakpoints across DHRS1 (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 METTL3 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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 | LUSC | TCGA-39-5019-01A | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
ChimerDB4 | LUSC | TCGA-39-5019 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
ChimerDB4 | LUSC | TCGA-39-5019-01A | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
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Fusion Gene ORF analysis for DHRS1-METTL3 |
Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
ORF | Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
intron-3CDS | ENST00000559088 | ENST00000298717 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
intron-3UTR | ENST00000559088 | ENST00000538267 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
intron-intron | ENST00000559088 | ENST00000545319 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
In-frame | ENST00000288111 | ENST00000298717 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
5CDS-3UTR | ENST00000288111 | ENST00000538267 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
5CDS-intron | ENST00000288111 | ENST00000545319 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
Frame-shift | ENST00000396813 | ENST00000298717 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
5CDS-3UTR | ENST00000396813 | ENST00000538267 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
5CDS-intron | ENST00000396813 | ENST00000545319 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - |
ORFfinder result based on the fusion transcript sequence of in-frame fusion genes. |
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) |
ENST00000288111 | DHRS1 | chr14 | 24768163 | - | ENST00000298717 | METTL3 | chr14 | 21970045 | - | 1567 | 427 | 277 | 1446 | 389 |
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 |
ENST00000288111 | ENST00000298717 | DHRS1 | chr14 | 24768163 | - | METTL3 | chr14 | 21970045 | - | 0.001945056 | 0.998055 |
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Fusion Genomic Features for DHRS1-METTL3 |
FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints. |
Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | 1-p | p (fusion gene breakpoint) |
Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page. |
Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page. |
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Fusion Protein Features for DHRS1-METTL3 |
Go to FGviewer for the breakpoints of chr14:24768163-chr14:21970045 - FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
DHRS1 | METTL3 |
FUNCTION: The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:27627798, PubMed:27373337, PubMed:27281194, PubMed:28297716, PubMed:30428350, PubMed:29506078, PubMed:29348140, PubMed:9409616). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (PubMed:27627798, PubMed:27373337, PubMed:27281194). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:28297716, PubMed:9409616). M6A acts as a key regulator of mRNA stability: methylation is completed upon the release of mRNA into the nucleoplasm and promotes mRNA destabilization and degradation (PubMed:28637692). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs (By similarity). M6A regulates the length of the circadian clock: acts as an early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop (By similarity). M6A also regulates circadian regulation of hepatic lipid metabolism (PubMed:30428350). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). Also required for oogenesis (By similarity). Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites (PubMed:28297716). M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation (By similarity). Inhibits the type I interferon response by mediating m6A methylation of IFNB (PubMed:30559377). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (PubMed:25799998). Mediates m6A methylation of Xist RNA, thereby participating in random X inactivation: m6A methylation of Xist leads to target YTHDC1 reader on Xist and promote transcription repression activity of Xist (PubMed:27602518). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (PubMed:25799998). Acts as a positive regulator of mRNA translation independently of the methyltransferase activity: promotes translation by interacting with the translation initiation machinery in the cytoplasm (PubMed:27117702). Its overexpression in a number of cancer cells suggests that it may participate in cancer cell proliferation by promoting mRNA translation (PubMed:27117702). {ECO:0000250|UniProtKB:Q8C3P7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:25799998, ECO:0000269|PubMed:26321680, ECO:0000269|PubMed:26593424, ECO:0000269|PubMed:27117702, ECO:0000269|PubMed:27281194, ECO:0000269|PubMed:27373337, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:27627798, ECO:0000269|PubMed:28297716, ECO:0000269|PubMed:28637692, ECO:0000269|PubMed:29348140, ECO:0000269|PubMed:29506078, ECO:0000269|PubMed:30428350, ECO:0000269|PubMed:30559377, ECO:0000269|PubMed:9409616}. |
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. |
- In-frame and 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 |
Tgene | METTL3 | chr14:24768163 | chr14:21970045 | ENST00000298717 | 2 | 11 | 377_378 | 241.0 | 581.0 | Region | S-adenosyl-L-methionine binding | |
Tgene | METTL3 | chr14:24768163 | chr14:21970045 | ENST00000298717 | 2 | 11 | 396_410 | 241.0 | 581.0 | Region | Gate loop 1 | |
Tgene | METTL3 | chr14:24768163 | chr14:21970045 | ENST00000298717 | 2 | 11 | 465_478 | 241.0 | 581.0 | Region | Positively charged region required for RNA-binding | |
Tgene | METTL3 | chr14:24768163 | chr14:21970045 | ENST00000298717 | 2 | 11 | 507_515 | 241.0 | 581.0 | Region | Gate loop 2 | |
Tgene | METTL3 | chr14:24768163 | chr14:21970045 | ENST00000298717 | 2 | 11 | 536_539 | 241.0 | 581.0 | Region | S-adenosyl-L-methionine binding | |
Tgene | METTL3 | chr14:24768163 | chr14:21970045 | ENST00000298717 | 2 | 11 | 549_550 | 241.0 | 581.0 | Region | S-adenosyl-L-methionine binding |
- In-frame and 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 |
Tgene | METTL3 | chr14:24768163 | chr14:21970045 | ENST00000298717 | 2 | 11 | 210_215 | 241.0 | 581.0 | Motif | Nuclear localization signal |
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Fusion Gene Sequence for DHRS1-METTL3 |
For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
>In-frame_ENST00000288111_ENST00000298717_TCGA-39-5019-01A_DHRS1_chr14_24768163_-_METTL3_chr14_21970045_length(transcript)=1567nt_BP=427nt TACTACGTCATAGTTCCGCGCCGCCCCAGCCGGGCGGGGTGGGTGTGTCACCCAGATCGCTCCGCCCCCATCCGCAGGTTCTAACTTTGG CCTGGGACTCTGCCCCTCTACCTCAGCACAGAATCGCCCCGGGTCCTACTACAGAATCAATCCTTGAACACTGCCTCCACGTCGCCGGCT CAATCTGGGCGAGAACCCAGACTTCCACCGCAGCCCCGCAATCTGCAGACCTCAGCGGCAGCGCAGGTGGCAGACCTGCCTCCTTTGCCT GTGAGTCATGGCAGCTCCCATGAATGGCCAAGTGTGTGTGGTGACTGGTGCCTCCAGGGGTATTGGCCGTGGCATTGCCTTGCAGCTCTG CAAAGCAGGCGCCACAGTTTACATCACTGGCCGCCATCTGGACACCCTTCGCGTTGTTGCTCAGGAGGTCAGTCAGGAGATCCTAGAGCT ATTAAATACTACAACAGCCAAGGAACAATCCATTGTTGAAAAATTTCGCTCTCGAGGTCGGGCCCAAGTGCAAGAATTCTGTGACTATGG AACCAAGGAGGAGTGCATGAAAGCCAGTGATGCTGATCGACCCTGTCGCAAGCTGCACTTCAGACGAATTATCAATAAACACACTGATGA GTCTTTAGGTGACTGCTCTTTCCTTAATACATGTTTCCACATGGATACCTGCAAGTATGTTCACTATGAAATTGATGCTTGCATGGATTC TGAGGCCCCTGGCAGCAAAGACCACACGCCAAGCCAGGAGCTTGCTCTTACACAGAGTGTCGGAGGTGATTCCAGTGCAGACCGACTCTT CCCACCTCAGTGGATCTGTTGTGATATCCGCTACCTGGACGTCAGTATCTTGGGCAAGTTTGCAGTTGTGATGGCTGACCCACCCTGGGA TATTCACATGGAACTGCCCTATGGGACCCTGACAGATGATGAGATGCGCAGGCTCAACATACCCGTACTACAGGATGATGGCTTTCTCTT CCTCTGGGTCACAGGCAGGGCCATGGAGTTGGGGAGAGAATGTCTAAATCTCTGGGGGTATGAACGGGTAGATGAAATTATTTGGGTGAA GACAAATCAACTGCAACGCATCATTCGGACAGGCCGTACAGGTCACTGGTTGAACCATGGGAAGGAACACTGCTTGGTTGGTGTCAAAGG AAATCCCCAAGGCTTCAACCAGGGTCTGGATTGTGATGTGATCGTAGCTGAGGTTCGTTCCACCAGTCATAAACCAGATGAAATCTATGG CATGATTGAAAGACTATCTCCTGGCACTCGCAAGATTGAGTTATTTGGACGACCACACAATGTGCAACCCAACTGGATCACCCTTGGAAA CCAACTGGATGGGATCCACCTACTAGACCCAGATGTGGTTGCACGGTTCAAGCAAAGGTACCCAGATGGTATCATCTCTAAACCTAAGAA TTTATAGAAGCACTTCCTTACAGAGCTAAGAATCCATAGCCATGGCTCTGTAAGCTAAACCTGAAGAGTGATATTTGTACAATAGCTTTC >In-frame_ENST00000288111_ENST00000298717_TCGA-39-5019-01A_DHRS1_chr14_24768163_-_METTL3_chr14_21970045_length(amino acids)=389AA_start in transcript=277_stop in transcript=1446 MAAPMNGQVCVVTGASRGIGRGIALQLCKAGATVYITGRHLDTLRVVAQEVSQEILELLNTTTAKEQSIVEKFRSRGRAQVQEFCDYGTK EECMKASDADRPCRKLHFRRIINKHTDESLGDCSFLNTCFHMDTCKYVHYEIDACMDSEAPGSKDHTPSQELALTQSVGGDSSADRLFPP QWICCDIRYLDVSILGKFAVVMADPPWDIHMELPYGTLTDDEMRRLNIPVLQDDGFLFLWVTGRAMELGRECLNLWGYERVDEIIWVKTN QLQRIIRTGRTGHWLNHGKEHCLVGVKGNPQGFNQGLDCDVIVAEVRSTSHKPDEIYGMIERLSPGTRKIELFGRPHNVQPNWITLGNQL -------------------------------------------------------------- |
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Fusion Gene PPI Analysis for DHRS1-METTL3 |
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 (BIOGRID-3.4.160) |
Hgene | Hgene's interactors | Tgene | Tgene's interactors |
- Retained PPIs in in-frame fusion. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
Tgene | METTL3 | chr14:24768163 | chr14:21970045 | ENST00000298717 | 2 | 11 | 450_454 | 241.0 | 581.0 | METTL14 | |
Tgene | METTL3 | chr14:24768163 | chr14:21970045 | ENST00000298717 | 2 | 11 | 464_480 | 241.0 | 581.0 | METTL14 |
- Lost PPIs in in-frame fusion. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
- Retained PPIs, but lost function due to frame-shift fusion. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs for DHRS1-METTL3 |
Drugs targeting genes involved in this fusion gene. (DrugBank Version 5.1.8 2021-05-08) |
Partner | Gene | UniProtAcc | DrugBank ID | Drug name | Drug activity | Drug type | Drug status |
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Related Diseases for DHRS1-METTL3 |
Diseases associated with fusion partners. (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |