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Fusion gene ID: 18514 |
FusionGeneSummary for KDM6A_RPS6KA3 |
 Fusion gene summary |
| Fusion gene information | Fusion gene name: KDM6A_RPS6KA3 | Fusion gene ID: 18514 | Hgene | Tgene | Gene symbol | KDM6A | RPS6KA3 | Gene ID | 7403 | 6197 |
| Gene name | lysine demethylase 6A | ribosomal protein S6 kinase A3 | |
| Synonyms | KABUK2|UTX|bA386N14.2 | CLS|HU-3|ISPK-1|MAPKAPK1B|MRX19|RSK|RSK2|S6K-alpha3|p90-RSK2|pp90RSK2 | |
| Cytomap | Xp11.3 | Xp22.12 | |
| Type of gene | protein-coding | protein-coding | |
| Description | lysine-specific demethylase 6AbA386N14.2 (ubiquitously transcribed X chromosome tetratricopeptide repeat protein (UTX))histone demethylase UTXlysine (K)-specific demethylase 6Aubiquitously transcribed tetratricopeptide repeat protein X-linkedubiquito | ribosomal protein S6 kinase alpha-3MAP kinase-activated protein kinase 1bMAPK-activated protein kinase 1bMAPKAP kinase 1bMAPKAPK-1bRSK-2S6K-alpha-3insulin-stimulated protein kinase 1p90-RSK 3ribosomal S6 kinase 2ribosomal protein S6 kinase, 90kD | |
| Modification date | 20180523 | 20180523 | |
| UniProtAcc | O15550 | P51812 | |
| Ensembl transtripts involved in fusion gene | ENST00000377967, ENST00000382899, ENST00000536777, ENST00000543216, ENST00000479423, | ENST00000379565, ENST00000544447, ENST00000379548, ENST00000540702, ENST00000479809, | |
| Fusion gene scores | * DoF score | 13 X 7 X 9=819 | 4 X 4 X 2=32 |
| # samples | 12 | 4 | |
| ** MAII score | log2(12/819*10)=-2.77082904603249 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(4/32*10)=0.321928094887362 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | |
| Context | PubMed: KDM6A [Title/Abstract] AND RPS6KA3 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Functional or gene categories assigned by FusionGDB annotation | Tumor suppressor gene involved fusion gene, retained protein feature but frameshift. DDR (DNA damage repair) gene involved fusion gene, in-frame but not retained their domain. | ||
| * 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 | RPS6KA3 | GO:0043154 | negative regulation of cysteine-type endopeptidase activity involved in apoptotic process | 18402937 |
| Fusion gene information from three resources (ChiTars (NAR, 2018), tumorfusions (NAR, 2018), Gao et al. (Cell, 2018)) * 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. |
| Data type | Source | Cancer type | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| TCGA | RV | SARC | TCGA-DX-A3UC-01A | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| * LD: Li Ding group's fusion gene list RV: Roel Verhaak group's fusion gene list ChiTaRs fusion database |
| 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 |
| Frame-shift | ENST00000377967 | ENST00000379565 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-5UTR | ENST00000377967 | ENST00000544447 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-intron | ENST00000377967 | ENST00000379548 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-5UTR | ENST00000377967 | ENST00000540702 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-intron | ENST00000377967 | ENST00000479809 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| Frame-shift | ENST00000382899 | ENST00000379565 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-5UTR | ENST00000382899 | ENST00000544447 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-intron | ENST00000382899 | ENST00000379548 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-5UTR | ENST00000382899 | ENST00000540702 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-intron | ENST00000382899 | ENST00000479809 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| Frame-shift | ENST00000536777 | ENST00000379565 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-5UTR | ENST00000536777 | ENST00000544447 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-intron | ENST00000536777 | ENST00000379548 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-5UTR | ENST00000536777 | ENST00000540702 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-intron | ENST00000536777 | ENST00000479809 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| Frame-shift | ENST00000543216 | ENST00000379565 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-5UTR | ENST00000543216 | ENST00000544447 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-intron | ENST00000543216 | ENST00000379548 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-5UTR | ENST00000543216 | ENST00000540702 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| 5CDS-intron | ENST00000543216 | ENST00000479809 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| intron-3CDS | ENST00000479423 | ENST00000379565 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| intron-5UTR | ENST00000479423 | ENST00000544447 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| intron-intron | ENST00000479423 | ENST00000379548 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| intron-5UTR | ENST00000479423 | ENST00000540702 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
| intron-intron | ENST00000479423 | ENST00000479809 | KDM6A | chrX | 44950109 | + | RPS6KA3 | chrX | 20252932 | - |
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FusionProtFeatures for KDM6A_RPS6KA3 |
| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| KDM6A | RPS6KA3 |
| Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code(PubMed:17851529, PubMed:17713478, PubMed:17761849). Demethylatestrimethylated and dimethylated but not monomethylated H3 'Lys-27'(PubMed:17851529, PubMed:17713478, PubMed:17761849). Plays acentral role in regulation of posterior development, by regulatingHOX gene expression (PubMed:17851529). Demethylation of 'Lys-27'of histone H3 is concomitant with methylation of 'Lys-4' ofhistone H3, and regulates the recruitment of the PRC1 complex andmonoubiquitination of histone H2A (PubMed:17761849). Plays ademethylase-independent role in chromatin remodeling to regulateT-box family member-dependent gene expression (By similarity).{ECO:0000250|UniProtKB:O70546, ECO:0000269|PubMed:17713478,ECO:0000269|PubMed:17761849, ECO:0000269|PubMed:17851529,ECO:0000269|PubMed:18003914}. | Serine/threonine-protein kinase that acts downstream ofERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenicand stress-induced activation of the transcription factors CREB1,ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 andEIF4B phosphorylation, and mediates cellular proliferation,survival, and differentiation by modulating mTOR signaling andrepressing pro-apoptotic function of BAD and DAPK1. In fibroblast,is required for EGF-stimulated phosphorylation of CREB1 andhistone H3 at 'Ser-10', which results in the subsequenttranscriptional activation of several immediate-early genes. Inresponse to mitogenic stimulation (EGF and PMA), phosphorylatesand activates NR4A1/NUR77 and ETV1/ER81 transcription factors andthe cofactor CREBBP. Upon insulin-derived signal, acts indirectlyon the transcription regulation of several genes byphosphorylating GSK3B at 'Ser-9' and inhibiting its activity.Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation byfacilitating assembly of the preinitiation complex. In response toinsulin, phosphorylates EIF4B, enhancing EIF4B affinity for theEIF3 complex and stimulating cap-dependent translation. Isinvolved in the mTOR nutrient-sensing pathway by directlyphosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2ability to suppress mTOR signaling, and mediates phosphorylationof RPTOR, which regulates mTORC1 activity and may promoterapamycin-sensitive signaling independently of the PI3K/AKTpathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellatecells by phosphorylating CEBPB in response to the hepatotoxincarbon tetrachloride (CCl4). Is involved in cell cycle regulationby phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1Bassociation with 14-3-3 proteins and prevents its translocation tothe nucleus and inhibition of G1 progression. In LPS-stimulateddendritic cells, is involved in TLR4-induced macropinocytosis, andin myeloma cells, acts as effector of FGFR3-mediatedtransformation signaling, after direct phosphorylation at Tyr-529by FGFR3. Negatively regulates EGF-induced MAPK1/3 phosphorylationvia phosphorylation of SOS1. Phosphorylates SOS1 at 'Ser-1134' and'Ser-1161' that create YWHAB and YWHAE binding sites and whichcontribute to the negative regulation of MAPK1/3 phosphorylation(By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630).{ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156,ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362,ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121,ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835,ECO:0000269|PubMed:9770464}. |
| 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 |
| - 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 |
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FusionGeneSequence for KDM6A_RPS6KA3 |
| For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. (nt: nucleotides, aa: amino acids) |
| * Fusion amino acid sequences. |
| * Fusion transcript sequences (only coding sequence (CDS) region). |
| * Fusion transcript sequences (Full-length transcript). |
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FusionGenePPI for KDM6A_RPS6KA3 |
| 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 |
| KDM6A | TLE1, KMT2D, KMT2C, NCOA6, N4BP2, PAXIP1, PPP6R3, ZNF281, PROSER1, ASH2L, RBBP5, WDR5, HIST3H3, WDR82, HIST1H3A, SRF, TBX5, NKX2-5, GATA4, SMARCA4, HIST2H3C, SMAD9, TP53, MAFA, MAFB, RNF2, ATM, MSH6, FNTA, PTEN, EYA2, ARHGAP22, FOXA1 | RPS6KA3 | PEA15, CREBBP, MAPK1, MAPK3, PDPK1, MAPK14, H2AFX, NEDD4, EIF3C, ATP5J, BARX1, MASP1, SMS, ESR1, YBX1, NFATC1, NFKBIA, TRAF2, MAPT, HSP90AA1, HIST1H3A, HMGN1, FGFR1, DFFA, HSPA8, NAPRT, RASAL1, CSE1L, GDA, NPEPPS, TGM2, SLC9A3R1, RPS6KA1, EGFR, ZMYM5, KIAA1456, TMEM139, HNRNPH1, STIP1, NTRK1, GBA, CDC37, MISP, FGFR2, FYN, TRIM11, IL17RA, WDYHV1, SPRED2, PPP6R2, STRADB, NDEL1, IRGC |
| - Retained PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - 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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RelatedDrugs for KDM6A_RPS6KA3 |
| Drugs targeting genes involved in this fusion gene. (DrugBank Version 5.1.0 2018-04-02) |
| Partner | Gene | UniProtAcc | DrugBank ID | Drug name | Drug activity | Drug type | Drug status |
| Tgene | RPS6KA3 | P51812 | DB00945 | Acetylsalicylic acid | Ribosomal protein S6 kinase alpha-3 | small molecule | approved|vet_approved |
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RelatedDiseases for KDM6A_RPS6KA3 |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Hgene | KDM6A | C0005695 | Bladder Neoplasm | 1 | CTD_human |
| Hgene | KDM6A | C0007138 | Carcinoma, Transitional Cell | 1 | CTD_human |
| Hgene | KDM6A | C0010606 | Adenoid Cystic Carcinoma | 1 | CTD_human |
| Hgene | KDM6A | C0279626 | Squamous cell carcinoma of esophagus | 1 | CTD_human |
| Tgene | RPS6KA3 | C0265252 | Coffin-Lowry syndrome | 6 | CTD_human;ORPHANET;UNIPROT |
| Tgene | RPS6KA3 | C0796225 | Mental Retardation, X-Linked 19 | 2 | UNIPROT |
| Tgene | RPS6KA3 | C0005941 | Bone Diseases, Developmental | 1 | CTD_human |
| Tgene | RPS6KA3 | C0027626 | Neoplasm Invasiveness | 1 | CTD_human |
| Tgene | RPS6KA3 | C0027627 | Neoplasm Metastasis | 1 | CTD_human |
| Tgene | RPS6KA3 | C0033922 | Psychomotor Disorders | 1 | CTD_human |
| Tgene | RPS6KA3 | C2239176 | Liver carcinoma | 1 | CTD_human |
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