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Fusion Protein:KDM4A-EGLN1 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: KDM4A-EGLN1 | FusionPDB ID: 41779 | FusionGDB2.0 ID: 41779 | Hgene | Tgene | Gene symbol | KDM4A | EGLN1 | Gene ID | 9682 | 54583 |
| Gene name | lysine demethylase 4A | egl-9 family hypoxia inducible factor 1 | |
| Synonyms | JHDM3A|JMJD2|JMJD2A|TDRD14A | C1orf12|ECYT3|HALAH|HIF-PH2|HIFPH2|HPH-2|HPH2|PHD2|SM20|ZMYND6 | |
| Cytomap | 1p34.2-p34.1 | 1q42.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | lysine-specific demethylase 4AjmjC domain-containing histone demethylation protein 3Ajumonji C domain-containing histone demethylase 3Ajumonji domain containing 2jumonji domain containing 2Ajumonji domain-containing protein 2Alysine (K)-specific dem | egl nine homolog 1HIF-prolyl hydroxylase 2egl nine-like protein 1hypoxia-inducible factor prolyl hydroxylase 2prolyl hydroxylase domain-containing protein 2zinc finger MYND domain-containing protein 6 | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | O75164 | Q9GZT9 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000463151, ENST00000372396, | ENST00000366641, ENST00000476717, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 13 X 11 X 10=1430 | 7 X 4 X 5=140 |
| # samples | 15 | 7 | |
| ** MAII score | log2(15/1430*10)=-3.25298074116987 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(7/140*10)=-1 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: KDM4A [Title/Abstract] AND EGLN1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | KDM4A(44126083)-EGLN1(231509845), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | KDM4A-EGLN1 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. KDM4A-EGLN1 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. KDM4A-EGLN1 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. KDM4A-EGLN1 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 | KDM4A | GO:0016577 | histone demethylation | 16024779 |
| Hgene | KDM4A | GO:0045892 | negative regulation of transcription, DNA-templated | 16024779 |
| Hgene | KDM4A | GO:0070544 | histone H3-K36 demethylation | 21914792 |
| Tgene | EGLN1 | GO:0001666 | response to hypoxia | 16956324 |
| Tgene | EGLN1 | GO:0018401 | peptidyl-proline hydroxylation to 4-hydroxy-L-proline | 11598268 |
| Tgene | EGLN1 | GO:0032364 | oxygen homeostasis | 16956324 |
| Tgene | EGLN1 | GO:0043433 | negative regulation of DNA-binding transcription factor activity | 16956324 |
| Tgene | EGLN1 | GO:0071731 | response to nitric oxide | 21601578 |
| Fusion gene breakpoints across KDM4A (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 EGLN1 (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 | LUSC | TCGA-43-8115-01A | KDM4A | chr1 | 44126083 | + | EGLN1 | chr1 | 231509845 | - |
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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) |
| ENST00000372396 | KDM4A | chr1 | 44126083 | + | ENST00000366641 | EGLN1 | chr1 | 231509845 | - | 3613 | 563 | 134 | 952 | 272 |
| 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 |
| ENST00000372396 | ENST00000366641 | KDM4A | chr1 | 44126083 | + | EGLN1 | chr1 | 231509845 | - | 0.000193508 | 0.99980646 |
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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 >41779_41779_1_KDM4A-EGLN1_KDM4A_chr1_44126083_ENST00000372396_EGLN1_chr1_231509845_ENST00000366641_length(amino acids)=272AA_BP=143 MASESETLNPSARIMTFYPTMEEFRNFSRYIAYIESQGAHRAGLAKVVPPKEWKPRASYDDIDDLVIPAPIQQLVTGQSGLFTQYNIQKK AMTVREFRKIANSDKYCTPRYSEFEELERKYWKNLTFNPPIYGADVNGTLYEKAMVACYPGNGTGYVRHVDNPNGDGRCVTCIYYLNKDW DAKVSGGILRIFPEGKAQFADIEPKFDRLLFFWSDRRNPHEVQPAYATRYAITVWYFDADERARAKVKYLTGEKGVRVELNKPSDSVGKD -------------------------------------------------------------- |
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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/chr1:44126083/chr1:231509845) - 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 |
| KDM4A | EGLN1 |
| FUNCTION: Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code (PubMed:26741168). Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively. {ECO:0000269|PubMed:16024779, ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:26741168}.; FUNCTION: [Isoform 2]: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain. {ECO:0000269|PubMed:21694756}. | FUNCTION: Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif. {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:12351678, ECO:0000269|PubMed:15897452, ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:21792862, ECO:0000269|PubMed:25129147}. |
| 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 | KDM4A | chr1:44126083 | chr1:231509845 | ENST00000372396 | + | 4 | 22 | 14_56 | 143.0 | 1065.0 | Domain | JmjN |
| - 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 | KDM4A | chr1:44126083 | chr1:231509845 | ENST00000372396 | + | 4 | 22 | 142_308 | 143.0 | 1065.0 | Domain | JmjC |
| Hgene | KDM4A | chr1:44126083 | chr1:231509845 | ENST00000372396 | + | 4 | 22 | 897_954 | 143.0 | 1065.0 | Domain | Note=Tudor 1 |
| Hgene | KDM4A | chr1:44126083 | chr1:231509845 | ENST00000372396 | + | 4 | 22 | 955_1011 | 143.0 | 1065.0 | Domain | Note=Tudor 2 |
| Hgene | KDM4A | chr1:44126083 | chr1:231509845 | ENST00000372396 | + | 4 | 22 | 709_767 | 143.0 | 1065.0 | Zinc finger | Note=PHD-type 1 |
| Hgene | KDM4A | chr1:44126083 | chr1:231509845 | ENST00000372396 | + | 4 | 22 | 772_805 | 143.0 | 1065.0 | Zinc finger | C2HC pre-PHD-type |
| Hgene | KDM4A | chr1:44126083 | chr1:231509845 | ENST00000372396 | + | 4 | 22 | 828_885 | 143.0 | 1065.0 | Zinc finger | PHD-type 2 |
| Tgene | EGLN1 | chr1:44126083 | chr1:231509845 | ENST00000366641 | 0 | 5 | 291_392 | 297.0 | 427.0 | Domain | Fe2OG dioxygenase | |
| Tgene | EGLN1 | chr1:44126083 | chr1:231509845 | ENST00000366641 | 0 | 5 | 241_251 | 297.0 | 427.0 | Region | Beta(2)beta(3) 'finger-like' loop | |
| Tgene | EGLN1 | chr1:44126083 | chr1:231509845 | ENST00000366641 | 0 | 5 | 6_20 | 297.0 | 427.0 | Region | Note=Required for nuclear export | |
| Tgene | EGLN1 | chr1:44126083 | chr1:231509845 | ENST00000366641 | 0 | 5 | 21_58 | 297.0 | 427.0 | Zinc finger | MYND-type |
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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 |
| KDM4A | |
| EGLN1 |
| - 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 | KDM4A | chr1:44126083 | chr1:231509845 | ENST00000372396 | + | 4 | 22 | 597_638 | 143.0 | 1065.0 | NCOR1 |
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Related Drugs to KDM4A-EGLN1 |
| 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 KDM4A-EGLN1 |
| 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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