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Fusion gene ID: 1561 |
FusionGeneSummary for ALK_RPA1 |
 Fusion gene summary |
| Fusion gene information | Fusion gene name: ALK_RPA1 | Fusion gene ID: 1561 | Hgene | Tgene | Gene symbol | ALK | RPA1 | Gene ID | 238 | 25885 |
| Gene name | ALK receptor tyrosine kinase | RNA polymerase I subunit A | |
| Synonyms | CD246|NBLST3 | A190|AFDCIN|RPA1|RPA194|RPO1-4|RPO14 | |
| Cytomap | 2p23.2-p23.1 | 2p11.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | ALK tyrosine kinase receptorCD246 antigenanaplastic lymphoma receptor tyrosine kinasemutant anaplastic lymphoma kinase | DNA-directed RNA polymerase I subunit RPA1DNA-directed RNA polymerase I largest subunitDNA-directed RNA polymerase I subunit ADNA-directed RNA polymerase I subunit A1RNA polymerase I 194 kDa subunitpolymerase (RNA) I polypeptide A, 194kDapolymerase | |
| Modification date | 20180527 | 20180523 | |
| UniProtAcc | Q9UM73 | P27694 | |
| Ensembl transtripts involved in fusion gene | ENST00000389048, ENST00000431873, ENST00000498037, | ENST00000254719, ENST00000573924, | |
| Fusion gene scores | * DoF score | 6 X 6 X 3=108 | 8 X 7 X 3=168 |
| # samples | 6 | 8 | |
| ** MAII score | log2(6/108*10)=-0.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(8/168*10)=-1.0703893278914 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context | PubMed: ALK [Title/Abstract] AND RPA1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Functional or gene categories assigned by FusionGDB annotation | |||
| * 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 | ALK | GO:0016310 | phosphorylation | 9174053 |
| Hgene | ALK | GO:0046777 | protein autophosphorylation | 9174053 |
| 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 |
| ChiTaRS3.1 | BF945806 | ALK | chr2 | 29478958 | - | RPA1 | chr17 | 1779045 | + |
| * 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 |
| intron-3CDS | ENST00000389048 | ENST00000254719 | ALK | chr2 | 29478958 | - | RPA1 | chr17 | 1779045 | + |
| intron-3UTR | ENST00000389048 | ENST00000573924 | ALK | chr2 | 29478958 | - | RPA1 | chr17 | 1779045 | + |
| intron-3CDS | ENST00000431873 | ENST00000254719 | ALK | chr2 | 29478958 | - | RPA1 | chr17 | 1779045 | + |
| intron-3UTR | ENST00000431873 | ENST00000573924 | ALK | chr2 | 29478958 | - | RPA1 | chr17 | 1779045 | + |
| intron-3CDS | ENST00000498037 | ENST00000254719 | ALK | chr2 | 29478958 | - | RPA1 | chr17 | 1779045 | + |
| intron-3UTR | ENST00000498037 | ENST00000573924 | ALK | chr2 | 29478958 | - | RPA1 | chr17 | 1779045 | + |
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FusionProtFeatures for ALK_RPA1 |
| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| ALK | RPA1 |
| Neuronal receptor tyrosine kinase that is essentiallyand transiently expressed in specific regions of the central andperipheral nervous systems and plays an important role in thegenesis and differentiation of the nervous system. Transducessignals from ligands at the cell surface, through specificactivation of the mitogen-activated protein kinase (MAPK) pathway.Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK inducestyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well asof the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptorfor ligands pleiotrophin (PTN), a secreted growth factor, andmidkine (MDK), a PTN-related factor, thus participating in PTN andMDK signal transduction. PTN-binding induces MAPK pathwayactivation, which is important for the anti-apoptotic signaling ofPTN and regulation of cell proliferation. MDK-binding inducesphosphorylation of the ALK target insulin receptor substrate(IRS1), activates mitogen-activated protein kinases (MAPKs) andPI3-kinase, resulting also in cell proliferation induction. DrivesNF-kappa-B activation, probably through IRS1 and the activation ofthe AKT serine/threonine kinase. Recruitment of IRS1 to activatedALK and the activation of NF-kappa-B are essential for theautocrine growth and survival signaling of MDK.{ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720,ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760,ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009,ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:15908427,ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150,ECO:0000269|PubMed:17274988}. | As part of the heterotrimeric replication protein Acomplex (RPA/RP-A), binds and stabilizes single-stranded DNAintermediates, that form during DNA replication or upon DNAstress. It prevents their reannealing and in parallel, recruitsand activates different proteins and complexes involved in DNAmetabolism (PubMed:27723720, PubMed:27723717). Thereby, it playsan essential role both in DNA replication and the cellularresponse to DNA damage (PubMed:9430682). In the cellular responseto DNA damage, the RPA complex controls DNA repair and DNA damagecheckpoint activation. Through recruitment of ATRIP activates theATR kinase a master regulator of the DNA damage response(PubMed:24332808). It is required for the recruitment of the DNAdouble-strand break repair factors RAD51 and RAD52 to chromatin inresponse to DNA damage (PubMed:17765923). Also recruits to sitesof DNA damage proteins like XPA and XPG that are involved innucleotide excision repair and is required for this mechanism ofDNA repair (PubMed:7697716). Plays also a role in base excisionrepair (BER) probably through interaction with UNG(PubMed:9765279). Also recruits SMARCAL1/HARP, which is involvedin replication fork restart, to sites of DNA damage. May also playa role in telomere maintenance (PubMed:17959650). As part of thealternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared tothe RPA2-containing, canonical RPA complex, may not supportchromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNApolymerase alpha but could support DNA synthesis by polymerasedelta in presence of PCNA and replication factor C (RFC), the dualincision/excision reaction of nucleotide excision repair andRAD51-dependent strand exchange (PubMed:19996105).{ECO:0000269|PubMed:12791985, ECO:0000269|PubMed:17765923,ECO:0000269|PubMed:17959650, ECO:0000269|PubMed:19116208,ECO:0000269|PubMed:19996105, ECO:0000269|PubMed:24332808,ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720,ECO:0000269|PubMed:7697716, ECO:0000269|PubMed:7700386,ECO:0000269|PubMed:9430682, ECO:0000269|PubMed:9765279}. |
| 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 ALK_RPA1 |
| 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 ALK_RPA1 |
| 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 |
| - 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 ALK_RPA1 |
| 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 |
| Hgene | ALK | Q9UM73 | DB08865 | Crizotinib | ALK tyrosine kinase receptor | small molecule | approved |
| Hgene | ALK | Q9UM73 | DB09063 | Ceritinib | ALK tyrosine kinase receptor | small molecule | approved |
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RelatedDiseases for ALK_RPA1 |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Hgene | ALK | C0007131 | Non-Small Cell Lung Carcinoma | 28 | CTD_human |
| Hgene | ALK | C0027819 | Neuroblastoma | 12 | CTD_human;ORPHANET |
| Hgene | ALK | C0152013 | Adenocarcinoma of lung (disorder) | 8 | CTD_human |
| Hgene | ALK | C0206180 | Ki-1+ Anaplastic Large Cell Lymphoma | 6 | CTD_human |
| Hgene | ALK | C2751681 | NEUROBLASTOMA, SUSCEPTIBILITY TO, 3 | 4 | UNIPROT |
| Hgene | ALK | C0018199 | Granuloma, Plasma Cell | 3 | CTD_human |
| Hgene | ALK | C0007621 | Neoplastic Cell Transformation | 2 | CTD_human |
| Hgene | ALK | C0027627 | Neoplasm Metastasis | 2 | CTD_human |
| Hgene | ALK | C0001973 | Alcoholic Intoxication, Chronic | 1 | PSYGENET |
| Hgene | ALK | C0006118 | Brain Neoplasms | 1 | CTD_human |
| Hgene | ALK | C0007134 | Renal Cell Carcinoma | 1 | CTD_human |
| Hgene | ALK | C0011570 | Mental Depression | 1 | PSYGENET |
| Hgene | ALK | C0011581 | Depressive disorder | 1 | PSYGENET |
| Hgene | ALK | C0027643 | Neoplasm Recurrence, Local | 1 | CTD_human |
| Hgene | ALK | C0036341 | Schizophrenia | 1 | PSYGENET |
| Hgene | ALK | C0079744 | Diffuse Large B-Cell Lymphoma | 1 | CTD_human |
| Hgene | ALK | C0085269 | Plasma Cell Granuloma, Pulmonary | 1 | CTD_human |
| Hgene | ALK | C0278601 | Inflammatory Breast Carcinoma | 1 | CTD_human |
| Tgene | RPA1 | C0263454 | Chloracne | 1 | CTD_human |
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