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Fusion Protein:ZNF66-MLLT3 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: ZNF66-MLLT3 | FusionPDB ID: 102680 | FusionGDB2.0 ID: 102680 | Hgene | Tgene | Gene symbol | ZNF66 | MLLT3 | Gene ID | 7617 | 4300 |
| Gene name | zinc finger protein 66 | MLLT3 super elongation complex subunit | |
| Synonyms | ZNF66P | AF9|YEATS3 | |
| Cytomap | 19p12 | 9p21.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | putative zinc finger protein 66 | protein AF-9ALL1-fused gene from chromosome 9 proteinKMT2A/MLLT3 fusionKMT2A/MLLT3 fusion proteinYEATS domain-containing protein 3myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog); translocated to, 3myeloid/lymphoid or mixed-lineage leu | |
| Modification date | 20200313 | 20200327 | |
| UniProtAcc | . | P42568 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000344519, ENST00000360204, ENST00000425625, ENST00000594534, | ENST00000355930, ENST00000429426, ENST00000380321, ENST00000475957, ENST00000380338, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 1 X 1 X 1=1 | 18 X 37 X 9=5994 |
| # samples | 1 | 35 | |
| ** MAII score | log2(1/1*10)=3.32192809488736 | log2(35/5994*10)=-4.09809225668125 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: ZNF66 [Title/Abstract] AND MLLT3 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ZNF66(20976684)-MLLT3(20448264), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | ZNF66-MLLT3 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. ZNF66-MLLT3 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. ZNF66-MLLT3 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. ZNF66-MLLT3 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. ZNF66-MLLT3 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF. ZNF66-MLLT3 seems lost the major protein functional domain in Tgene partner, which is a CGC 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 | MLLT3 | GO:0045893 | positive regulation of transcription, DNA-templated | 25417107|27105114 |
| Tgene | MLLT3 | GO:0090090 | negative regulation of canonical Wnt signaling pathway | 19591803 |
| Fusion gene breakpoints across ZNF66 (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 MLLT3 (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 | LUAD | TCGA-69-7980-01A | ZNF66 | chr19 | 20976684 | + | MLLT3 | chr9 | 20448264 | - |
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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) |
| ENST00000360204 | ZNF66 | chr19 | 20976684 | + | ENST00000380338 | MLLT3 | chr9 | 20448264 | - | 7233 | 1024 | 1063 | 2454 | 463 |
| 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 |
| ENST00000360204 | ENST00000380338 | ZNF66 | chr19 | 20976684 | + | MLLT3 | chr9 | 20448264 | - | 0.000171084 | 0.99982893 |
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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 >102680_102680_1_ZNF66-MLLT3_ZNF66_chr19_20976684_ENST00000360204_MLLT3_chr9_20448264_ENST00000380338_length(amino acids)=463AA_BP= MHLEGHPPVNHLRCEKLTFNNPTEDFRRKLLKAGGDPNRSIHTSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSTSFSK PHKLMKEHKEKPSKDSREHKSAFKEPSRDHNKSSKESSKKPKENKPLKEEKIVPKMAFKEPKPMSKEPKPDSNLLTITSGQDKKAPSKRP PISDSEELSAKKRKKSSSEALFKSFSSAPPLILTCSADKKQIKDKSHVKMGKVKIESETSEKKKSTLPPFDDIVDPNDSDVEENISSKSD SEQPSPASSSSSSSSSFTPSQTRQQGPLRSIMKDLHSDDNEEESDEVEDNDNDSEMERPVNRGGSRSRRVSLSDGSDSESSSASSPLHHE PPPPLLKTNNNQILEVKSPIKQSKSDKQIKNGECDKAYLDELVELHRRLMTLRERHILQQIVNLIEETGHFHITNTTFDFDLCSLDKTTV -------------------------------------------------------------- |
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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/chr19:20976684/chr9:20448264) - 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 |
| . | MLLT3 |
| 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: Chromatin reader component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA (PubMed:20159561, PubMed:20471948, PubMed:25417107, PubMed:27105114, PubMed:27545619). Specifically recognizes and binds acylated histone H3, with a preference for histone H3 that is crotonylated (PubMed:25417107, PubMed:27105114, PubMed:27545619, PubMed:30374167, PubMed:30385749). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25417107, PubMed:27105114, PubMed:27545619). Recognizes and binds histone H3 crotonylated at 'Lys-9' (H3K9cr), and with slightly lower affinity histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114). Also recognizes and binds histone H3 acetylated and butyrylated at 'Lys-9' (H3K9ac and H3K9bu, respectively), but with lower affinity than crotonylated histone H3 (PubMed:25417107, PubMed:27105114, PubMed:30385749). In the SEC complex, MLLT3 is required to recruit the complex to crotonylated histones (PubMed:27105114, PubMed:27545619). Recruitment of the SEC complex to crotonylated histones promotes recruitment of DOT1L on active chromatin to deposit histone H3 'Lys-79' methylation (H3K79me) (PubMed:25417107). Plays a key role in hematopoietic stem cell (HSC) maintenance by preserving, rather than confering, HSC stemness (PubMed:31776511). Acts by binding to the transcription start site of active genes in HSCs and sustaining level of H3K79me2, probably by recruiting DOT1L (PubMed:31776511). {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:27545619, ECO:0000269|PubMed:30374167, ECO:0000269|PubMed:30385749, ECO:0000269|PubMed:31776511}. |
| 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 | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 4_75 | 75.33333333333333 | 574.0 | Domain | KRAB |
| Tgene | MLLT3 | chr19:20976684 | chr9:20448264 | ENST00000380338 | 2 | 11 | 149_194 | 92.0 | 569.0 | Compositional bias | Note=Poly-Ser | |
| Tgene | MLLT3 | chr19:20976684 | chr9:20448264 | ENST00000380338 | 2 | 11 | 383_391 | 92.0 | 569.0 | Compositional bias | Note=Poly-Ser | |
| Tgene | MLLT3 | chr19:20976684 | chr9:20448264 | ENST00000380338 | 2 | 11 | 466_469 | 92.0 | 569.0 | Compositional bias | Note=Poly-Pro | |
| Tgene | MLLT3 | chr19:20976684 | chr9:20448264 | ENST00000380338 | 2 | 11 | 295_300 | 92.0 | 569.0 | Motif | Nuclear localization signal | |
| Tgene | MLLT3 | chr19:20976684 | chr9:20448264 | ENST00000380338 | 2 | 11 | 106_108 | 92.0 | 569.0 | Region | Histone H3K9cr binding | |
| Tgene | MLLT3 | chr19:20976684 | chr9:20448264 | ENST00000380338 | 2 | 11 | 106_109 | 92.0 | 569.0 | Region | Inhibitor XL-07i 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 | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 145_167 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 1%3B atypical |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 171_195 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 2 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 201_223 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 3 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 229_251 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 4 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 257_279 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 5 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 285_307 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 6 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 313_335 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 7 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 341_363 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 8 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 369_391 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 9 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 397_419 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 10 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 425_447 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 11 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 453_475 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 12 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 481_503 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 13 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 509_531 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 14 |
| Hgene | ZNF66 | chr19:20976684 | chr9:20448264 | ENST00000344519 | + | 3 | 4 | 537_559 | 75.33333333333333 | 574.0 | Zinc finger | C2H2-type 15 |
| Tgene | MLLT3 | chr19:20976684 | chr9:20448264 | ENST00000380338 | 2 | 11 | 1_138 | 92.0 | 569.0 | Domain | YEATS | |
| Tgene | MLLT3 | chr19:20976684 | chr9:20448264 | ENST00000380338 | 2 | 11 | 56_58 | 92.0 | 569.0 | Region | Inhibitor XL-07i binding | |
| Tgene | MLLT3 | chr19:20976684 | chr9:20448264 | ENST00000380338 | 2 | 11 | 78_80 | 92.0 | 569.0 | Region | Histone H3K9cr 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 |
| MLLT3 | APPBP2, MCM6, BCOR, RBM48, EEF1A1, PTN, LRIF1, DOT1L, SGK1, AFF4, AFF1, CDK9, AFF3, ACACA, SIRT1, CCNT1, NIPBL, EAF1, ELL3, PCGF1, MLLT1, EEF2, ELL, MLLT10, CCNT2, RNF2, KMT2A, CHD4, ELL2, PAF1, Cbx8, APP, CDK6, MED26, HSP90B1, EXOSC3, FAM9A, EDA, DENND2D, EPB41L3, XPO1, Aff1, Mllt1, H3F3A, PIP4K2A, EPB41L2, CAMKV, MLLT6, SNX24, BPIFB1, MDK, PES1, EPB41L5, ARRB2, ORF35, ALKBH4, LRRK2, HIST1H3A, KIAA1429, HHT1, DYRK1A, MIIP, VAX1, ZNF572, CCAR2, STH1, TULP3, COIL, FGF11, CT45A5, FGF12, RASA2, NDUFAF4, CREB3L3, SMOC1, SYT2, RNF151, PLCD4, CEP89, DAXX, EPB41L1, PLCD3, KCNE3, SULF2, SKP1, |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| ZNF66 | |
| MLLT3 |  |
| - 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 |
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Related Drugs to ZNF66-MLLT3 |
| 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 ZNF66-MLLT3 |
| 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 |
| Tgene | MLLT3 | C0005586 | Bipolar Disorder | 1 | PSYGENET |
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