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Kinase Fusion Gene:AHNAK_RPS6KA4 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: AHNAK_RPS6KA4 | KinaseFusionDB ID: KFG239 | FusionGDB2.0 ID: KFG239 | Hgene | Tgene | Gene symbol | AHNAK | RPS6KA4 | Gene ID | 79026 | 8986 | |
| Gene name | AHNAK nucleoprotein | ribosomal protein S6 kinase A4 | ||||||||||
| Synonyms | AHNAK1|AHNAKRS|PM227 | MSK2|RSK-B|S6K-alpha-4 | ||||||||||
| Cytomap | 11q12.3 | 11q13.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | neuroblast differentiation-associated protein AHNAKAHNAK-relateddesmoyokin | ribosomal protein S6 kinase alpha-490 kDa ribosomal protein S6 kinase 4mitogen- and stress-activated protein kinase 2nuclear mitogen- and stress-activated protein kinase 2ribosomal protein S6 kinase, 90kDa, polypeptide 4ribosomal protein kinase B | ||||||||||
| Modification date | 20240407 | 20240403 | ||||||||||
| UniProtAcc | Q09666 | O75676 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000525875, ENST00000257247, ENST00000378024, ENST00000530124, | ENST00000294261, ENST00000334205, ENST00000528057, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: AHNAK [Title/Abstract] AND RPS6KA4 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | AHNAK(62259204)-RPS6KA4(64132773), # samples:3 | |||||||||||
| 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 | RPS6KA4 | GO:0006355 | regulation of DNA-templated transcription | 9792677 |
| Tgene | RPS6KA4 | GO:0006468 | protein phosphorylation | 9792677 |
| Tgene | RPS6KA4 | GO:0035556 | intracellular signal transduction | 9792677 |
| Kinase Fusion gene breakpoints across AHNAK (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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| Kinase Fusion gene breakpoints across RPS6KA4 (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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Kinase Fusion Gene Sample Information |
| Kinase Fusion gene information. |
| Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE) * 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 | Sample | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp |
| ChimerDB4 | TCGA-A8-A09E-01A | AHNAK | chr11 | 62259204 | RPS6KA4 | chr11 | 64132773 |
| ChimerDB4 | TCGA-A8-A09E | AHNAK | chr11 | 62259203 | RPS6KA4 | chr11 | 64132772 |
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Kinase Fusion ORF Analysis |
| Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Seq length (transcript) | Seq length (amino acids) |
| ENST00000257247 | ENST00000528057 | AHNAK | chr11 | 62259204 | RPS6KA4 | chr11 | 64132773 | 2805 | 465 |
| ENST00000257247 | ENST00000528057 | AHNAK | chr11 | 62259203 | RPS6KA4 | chr11 | 64132772 | 2805 | 465 |
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Kinase Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq >ENST00000257247_ENST00000528057_AHNAK_chr11_62259204_RPS6KA4_chr11_64132773_length(amino acids)=465 MQGLDWVALAARKIPAPFRPQIRSELDVGNFAEEFTRLEPVYSPPGSPPPGDPRIFQGYSFVAPSILFDHNNAVMTDGLEAPGAGDRPGR AAVARSAMMQYELDLREPALGQGSFSVCRRCRQRQSGQEFAVKILSRRLEANTQREVAALRLCQSHPNVVNLHEVHHDQLHTYLVLELLR GGELLEHIRKKRHFSESEASQILRSLVSAVSFMHEEAGVVHRDLKPENILYADDTPGAPVKIIDFGFARLRPQSPGVPMQTPCFTLQYAA PELLAQQGYDESCDLWSLGVILYMMLSGQVPFQGASGQGGQSQAAEIMCKIREGRFSLDGEAWQGVSEEAKELVRGLLTVDPAKRLKLEG LRGSSWLQDGSARSSPPLRTPDVLESSGPAVRSGLNATFMAFNRGKREGFFLKSVENAPLAKRRKQKLRSATASRRGSPAPANPGRAPVA -------------------------------------------------------------- >ENST00000257247_ENST00000528057_AHNAK_chr11_62259203_RPS6KA4_chr11_64132772_length(amino acids)=465 MQGLDWVALAARKIPAPFRPQIRSELDVGNFAEEFTRLEPVYSPPGSPPPGDPRIFQGYSFVAPSILFDHNNAVMTDGLEAPGAGDRPGR AAVARSAMMQYELDLREPALGQGSFSVCRRCRQRQSGQEFAVKILSRRLEANTQREVAALRLCQSHPNVVNLHEVHHDQLHTYLVLELLR GGELLEHIRKKRHFSESEASQILRSLVSAVSFMHEEAGVVHRDLKPENILYADDTPGAPVKIIDFGFARLRPQSPGVPMQTPCFTLQYAA PELLAQQGYDESCDLWSLGVILYMMLSGQVPFQGASGQGGQSQAAEIMCKIREGRFSLDGEAWQGVSEEAKELVRGLLTVDPAKRLKLEG LRGSSWLQDGSARSSPPLRTPDVLESSGPAVRSGLNATFMAFNRGKREGFFLKSVENAPLAKRRKQKLRSATASRRGSPAPANPGRAPVA -------------------------------------------------------------- |
Multiple Sequence Alignment of All Fusion Protein Isoforms |
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Kinase 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/chr11:62259204/chr11:64132773) - 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 |
| AHNAK | RPS6KA4 |
| FUNCTION: May be required for neuronal cell differentiation. | FUNCTION: Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}. |
| 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 domain in the 5'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| Tgene | AHNAK | 62259203 | RPS6KA4 | 64132772 | ENST00000257247 | 7 | 17 | 302_371 | 302 | 773 | Domain | Note=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618 |
| Tgene | AHNAK | 62259204 | RPS6KA4 | 64132773 | ENST00000257247 | 7 | 17 | 302_371 | 302 | 773 | Domain | Note=AGC-kinase C-terminal;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00618 |
| Tgene | AHNAK | 62259203 | RPS6KA4 | 64132772 | ENST00000257247 | 7 | 17 | 411_674 | 302 | 773 | Domain | Note=Protein kinase 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Tgene | AHNAK | 62259204 | RPS6KA4 | 64132773 | ENST00000257247 | 7 | 17 | 411_674 | 302 | 773 | Domain | Note=Protein kinase 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
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Kinase Fusion Protein Structures |
| CIF files of the predicted kinase fusion proteins * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB) | Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | AA seq | Len(AA seq) |
| PDB file >>>TKFP_23_AHNAK_RPS6KA4 | ENST00000257247 | ENST00000528057 | AHNAK | chr11 | 62259204 | RPS6KA4 | chr11 | 64132773 | MQGLDWVALAARKIPAPFRPQIRSELDVGNFAEEFTRLEPVYSPPGSPPPGDPRIFQGYSFVAPSILFDHNNAVMTDGLEAPGAGDRPGR AAVARSAMMQYELDLREPALGQGSFSVCRRCRQRQSGQEFAVKILSRRLEANTQREVAALRLCQSHPNVVNLHEVHHDQLHTYLVLELLR GGELLEHIRKKRHFSESEASQILRSLVSAVSFMHEEAGVVHRDLKPENILYADDTPGAPVKIIDFGFARLRPQSPGVPMQTPCFTLQYAA PELLAQQGYDESCDLWSLGVILYMMLSGQVPFQGASGQGGQSQAAEIMCKIREGRFSLDGEAWQGVSEEAKELVRGLLTVDPAKRLKLEG LRGSSWLQDGSARSSPPLRTPDVLESSGPAVRSGLNATFMAFNRGKREGFFLKSVENAPLAKRRKQKLRSATASRRGSPAPANPGRAPVA | 465_AHNAK_RPS6KA4 |
| 3D view using mol* of TKFP_23_AHNAK_RPS6KA4 | ||||||||||
| PDB file >>>TKFP_24_AHNAK_RPS6KA4 | ENST00000257247 | ENST00000528057 | AHNAK | chr11 | 62259203 | RPS6KA4 | chr11 | 64132772 | MQGLDWVALAARKIPAPFRPQIRSELDVGNFAEEFTRLEPVYSPPGSPPPGDPRIFQGYSFVAPSILFDHNNAVMTDGLEAPGAGDRPGR AAVARSAMMQYELDLREPALGQGSFSVCRRCRQRQSGQEFAVKILSRRLEANTQREVAALRLCQSHPNVVNLHEVHHDQLHTYLVLELLR GGELLEHIRKKRHFSESEASQILRSLVSAVSFMHEEAGVVHRDLKPENILYADDTPGAPVKIIDFGFARLRPQSPGVPMQTPCFTLQYAA PELLAQQGYDESCDLWSLGVILYMMLSGQVPFQGASGQGGQSQAAEIMCKIREGRFSLDGEAWQGVSEEAKELVRGLLTVDPAKRLKLEG LRGSSWLQDGSARSSPPLRTPDVLESSGPAVRSGLNATFMAFNRGKREGFFLKSVENAPLAKRRKQKLRSATASRRGSPAPANPGRAPVA | 465_AHNAK_RPS6KA4 |
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Comparison of Fusion Protein Isoforms |
| Superimpose the 3D Structures Among All Fusion Protein Isoforms * Download the pdb file and open it from the molstar online viewer. |
| Comparison of the Secondary Structures of Fusion Protein Isoforms |
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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB |
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pLDDT score distribution |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. * The blue color at the bottom marks the best active site residues. |
| TKFP_23_AHNAK_RPS6KA4.png |
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Potential Active Site Information |
| The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite. |
| Kinase Fusion AA seq ID in KinaseFusionDB | Site score | Size | Dscore | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| TKFP_23_AHNAK_RPS6KA4 | 1.036 | 195 | 1.107 | 572.81 | 0.615 | 0.648 | 0.843 | 1.03 | 0.682 | 1.511 | 0.943 | Chain A: 34,35,38,39,40,41,43,60,62,65,67,68,69,70 ,71,75,88,89,90,92,93,105,107,112,113,114,115,116, 117,119,134,135,136,137,138,139,140,141,169,170,17 1 |
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Ramachandran Plot of Kinase Fusion Protein Structure |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide. |
| TKFP_23_AHNAK_RPS6KA4_ramachandran.png |
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Virtual Screening Results |
| Distribution of the average docking score across all approved kinase inhibitors. Distribution of the number of occurrence across all approved kinase inhibitors. |
| 5'-kinase fusion protein case |
| 3'-kinase fusion protein case |
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| Drug information from DrugBank of the top 20 interacting small molecules. * The detailed information of individual kinase inhibitors are available in the download page. |
| Fusion gene name info | Drug | Docking score | Glide g score | Glide energy |
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Kinase-Substrate Information of AHNAK_RPS6KA4 |
| Phosphorylation target of the kinase (phosphosite, 03-17-2024) |
| Kinase | Kinase UniProt Acc | Kinase species | Substrate | Substrate UniProt Acc | Substrate phosphorylated residues | Substrate phosphorylated sites (+/-7AA) | Domain |
| RPS6KA4 | O75676 | human | H3C1 | P68431 | S28 | ATkAArksAPATGGV | Histone |
| RPS6KA4 | O75676 | human | CREB1 | P16220 | S119 | EILsRRPsyRkILND | pKID |
| RPS6KA4 | O75676 | human | ATXN1 | P54253 | S775 | AtRKRRWsAPESRKL | |
| RPS6KA4 | O75676 | human | RELA | Q04206 | S276 | sMQLRRPsDRELsEP | RHD_dimer |
| RPS6KA4 | O75676 | human | RPS6KA4 | O75676 | S196 | EEkERtFsFCGTIEY | Pkinase |
| Biological Network Integration of This Kinase and Substrates (GeneMANIA website) |
| Enriched GO biological processes of the phosphorylation target genes of the kinase |
| Kinase | GOID | GO term | P.adjust |
| RPS6KA4 | ID | Description | 0.00e+00 |
| RPS6KA4 | GO:0035729 | cellular response to hepatocyte growth factor stimulus | 1.34e-03 |
| RPS6KA4 | GO:0035728 | response to hepatocyte growth factor | 1.34e-03 |
| RPS6KA4 | GO:0070498 | interleukin-1-mediated signaling pathway | 2.90e-03 |
| RPS6KA4 | GO:0071347 | cellular response to interleukin-1 | 2.42e-02 |
| RPS6KA4 | GO:0007613 | memory | 2.42e-02 |
| RPS6KA4 | GO:0070555 | response to interleukin-1 | 2.42e-02 |
| RPS6KA4 | GO:0014074 | response to purine-containing compound | 2.42e-02 |
| RPS6KA4 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 2.42e-02 |
| RPS6KA4 | GO:1901654 | response to ketone | 4.11e-02 |
| RPS6KA4 | GO:0051091 | positive regulation of DNA-binding transcription factor activity | 4.45e-02 |
| RPS6KA4 | GO:0007611 | learning or memory | 4.45e-02 |
| RPS6KA4 | GO:0060430 | lung saccule development | 4.45e-02 |
| RPS6KA4 | GO:0070391 | response to lipoteichoic acid | 4.45e-02 |
| RPS6KA4 | GO:0071223 | cellular response to lipoteichoic acid | 4.45e-02 |
| RPS6KA4 | GO:0050890 | cognition | 4.45e-02 |
| RPS6KA4 | GO:0033234 | negative regulation of protein sumoylation | 4.45e-02 |
| RPS6KA4 | GO:0061370 | testosterone biosynthetic process | 4.45e-02 |
| RPS6KA4 | GO:0010944 | negative regulation of transcription by competitive promoter binding | 4.45e-02 |
| RPS6KA4 | GO:0002357 | defense response to tumor cell | 4.45e-02 |
| RPS6KA4 | GO:0032494 | response to peptidoglycan | 4.45e-02 |
| RPS6KA4 | GO:1904321 | response to forskolin | 4.45e-02 |
| RPS6KA4 | GO:1904322 | cellular response to forskolin | 4.45e-02 |
| RPS6KA4 | GO:0032793 | positive regulation of CREB transcription factor activity | 4.45e-02 |
| RPS6KA4 | GO:0051090 | regulation of DNA-binding transcription factor activity | 4.45e-02 |
| RPS6KA4 | GO:0050862 | positive regulation of T cell receptor signaling pathway | 4.45e-02 |
| RPS6KA4 | GO:1901522 | positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus | 4.45e-02 |
| RPS6KA4 | GO:0016202 | regulation of striated muscle tissue development | 4.45e-02 |
| RPS6KA4 | GO:0043434 | response to peptide hormone | 4.45e-02 |
| RPS6KA4 | GO:0070431 | nucleotide-binding oligomerization domain containing 2 signaling pathway | 4.45e-02 |
| RPS6KA4 | GO:0009410 | response to xenobiotic stimulus | 4.45e-02 |
| RPS6KA4 | GO:0048732 | gland development | 4.45e-02 |
| RPS6KA4 | GO:0010720 | positive regulation of cell development | 4.45e-02 |
| RPS6KA4 | GO:1902004 | positive regulation of amyloid-beta formation | 4.45e-02 |
| RPS6KA4 | GO:0010224 | response to UV-B | 4.45e-02 |
| RPS6KA4 | GO:0010566 | regulation of ketone biosynthetic process | 4.45e-02 |
| RPS6KA4 | GO:0032495 | response to muramyl dipeptide | 4.45e-02 |
| RPS6KA4 | GO:0033762 | response to glucagon | 4.45e-02 |
| RPS6KA4 | GO:0048634 | regulation of muscle organ development | 4.45e-02 |
| RPS6KA4 | GO:0033233 | regulation of protein sumoylation | 4.45e-02 |
| RPS6KA4 | GO:0071294 | cellular response to zinc ion | 4.45e-02 |
| RPS6KA4 | GO:1901863 | positive regulation of muscle tissue development | 4.45e-02 |
| RPS6KA4 | GO:0035994 | response to muscle stretch | 4.45e-02 |
| RPS6KA4 | GO:1902894 | negative regulation of miRNA transcription | 4.45e-02 |
| RPS6KA4 | GO:1902993 | positive regulation of amyloid precursor protein catabolic process | 4.45e-02 |
| RPS6KA4 | GO:1904996 | positive regulation of leukocyte adhesion to vascular endothelial cell | 4.45e-02 |
| RPS6KA4 | GO:2000629 | negative regulation of miRNA metabolic process | 4.45e-02 |
| RPS6KA4 | GO:0045672 | positive regulation of osteoclast differentiation | 4.45e-02 |
| RPS6KA4 | GO:0050857 | positive regulation of antigen receptor-mediated signaling pathway | 4.45e-02 |
| RPS6KA4 | GO:0060479 | lung cell differentiation | 4.45e-02 |
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Related Drugs to AHNAK_RPS6KA4 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
| Distribution of the number of studies mentioning AHNAK-RPS6KA4 and kinase inhibitors the PubMed Abstract (04-01-2024) |
| Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
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Related Diseases to AHNAK_RPS6KA4 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Related diseases from the literature mentioned this fusion gene and drug. (PubMed, 04-01-2024) |
| MeSH ID | MeSH term |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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Clinical Trials of the Found Drugs/Small Molecules |
| Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024) |
| Clinical Trials from clinicaltrials.gov (06-17-2024) |
| Fusion Gene | Kinase Inhibitor | NCT ID | Study Status | Phases | Disease | # Enrolment | Date |
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