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Fusion Gene Summary | |
Fusion Gene ORF analysis | |
Fusion Genomic Features | |
Fusion Protein Features | |
Fusion Gene Sequence | |
Fusion Gene PPI analysis | |
Related Drugs | |
Related Diseases |
Fusion gene:LRRK2-MON2 (FusionGDB2 ID:50115) |
Fusion Gene Summary for LRRK2-MON2 |
Fusion gene summary |
Fusion gene information | Fusion gene name: LRRK2-MON2 | Fusion gene ID: 50115 | Hgene | Tgene | Gene symbol | LRRK2 | MON2 | Gene ID | 120892 | 23041 |
Gene name | leucine rich repeat kinase 2 | MON2 homolog, regulator of endosome-to-Golgi trafficking | |
Synonyms | AURA17|DARDARIN|PARK8|RIPK7|ROCO2 | - | |
Cytomap | 12q12 | 12q14.1 | |
Type of gene | protein-coding | protein-coding | |
Description | leucine-rich repeat serine/threonine-protein kinase 2augmented in rheumatoid arthritis 17 | protein MON2 homologMON2 regulator of endosome-to-Golgi trafficking | |
Modification date | 20200329 | 20200313 | |
UniProtAcc | Q5S007 | Q7Z3U7 | |
Ensembl transtripts involved in fusion gene | ENST00000298910, ENST00000343742, ENST00000481256, | ENST00000549378, ENST00000551397, ENST00000552115, ENST00000280379, ENST00000393629, ENST00000393630, ENST00000393632, ENST00000546600, ENST00000552738, | |
Fusion gene scores | * DoF score | 6 X 6 X 4=144 | 15 X 11 X 6=990 |
# samples | 6 | 17 | |
** MAII score | log2(6/144*10)=-1.26303440583379 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(17/990*10)=-2.54189377882927 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
Context | PubMed: LRRK2 [Title/Abstract] AND MON2 [Title/Abstract] AND fusion [Title/Abstract] | ||
Most frequent breakpoint | LRRK2(40637483)-MON2(62972225), # samples:1 | ||
Anticipated loss of major functional domain due to fusion event. | LRRK2-MON2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. LRRK2-MON2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. LRRK2-MON2 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. LRRK2-MON2 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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 |
Hgene | LRRK2 | GO:0000165 | MAPK cascade | 17200152 |
Hgene | LRRK2 | GO:0000186 | activation of MAPKK activity | 19302196 |
Hgene | LRRK2 | GO:0001934 | positive regulation of protein phosphorylation | 22012985 |
Hgene | LRRK2 | GO:0006468 | protein phosphorylation | 25500533 |
Hgene | LRRK2 | GO:0010955 | negative regulation of protein processing | 21370995 |
Hgene | LRRK2 | GO:0018105 | peptidyl-serine phosphorylation | 19576176 |
Hgene | LRRK2 | GO:0018107 | peptidyl-threonine phosphorylation | 21048939 |
Hgene | LRRK2 | GO:0031398 | positive regulation of protein ubiquitination | 16352719|20173330 |
Hgene | LRRK2 | GO:0032092 | positive regulation of protein binding | 21370995 |
Hgene | LRRK2 | GO:0034260 | negative regulation of GTPase activity | 22423108 |
Hgene | LRRK2 | GO:0043068 | positive regulation of programmed cell death | 17200152 |
Hgene | LRRK2 | GO:0046039 | GTP metabolic process | 21048939 |
Hgene | LRRK2 | GO:0046777 | protein autophosphorylation | 16269541|16321986|17200152|17442267 |
Hgene | LRRK2 | GO:1902499 | positive regulation of protein autoubiquitination | 16352719 |
Hgene | LRRK2 | GO:1903125 | negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation | 21850687 |
Hgene | LRRK2 | GO:1903215 | negative regulation of protein targeting to mitochondrion | 21370995 |
Fusion gene breakpoints across LRRK2 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
Fusion gene breakpoints across MON2 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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 | BLCA | TCGA-BT-A20X-01A | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
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Fusion Gene ORF analysis for LRRK2-MON2 |
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 |
5CDS-intron | ENST00000298910 | ENST00000549378 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
5CDS-intron | ENST00000298910 | ENST00000551397 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
5CDS-intron | ENST00000298910 | ENST00000552115 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
5CDS-intron | ENST00000343742 | ENST00000549378 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
5CDS-intron | ENST00000343742 | ENST00000551397 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
5CDS-intron | ENST00000343742 | ENST00000552115 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000298910 | ENST00000280379 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000298910 | ENST00000393629 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000298910 | ENST00000393630 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000298910 | ENST00000393632 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000298910 | ENST00000546600 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000298910 | ENST00000552738 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000343742 | ENST00000280379 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000343742 | ENST00000393629 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000343742 | ENST00000393630 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000343742 | ENST00000393632 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000343742 | ENST00000546600 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
Frame-shift | ENST00000343742 | ENST00000552738 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
intron-3CDS | ENST00000481256 | ENST00000280379 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
intron-3CDS | ENST00000481256 | ENST00000393629 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
intron-3CDS | ENST00000481256 | ENST00000393630 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
intron-3CDS | ENST00000481256 | ENST00000393632 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
intron-3CDS | ENST00000481256 | ENST00000546600 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
intron-3CDS | ENST00000481256 | ENST00000552738 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
intron-intron | ENST00000481256 | ENST00000549378 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
intron-intron | ENST00000481256 | ENST00000551397 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
intron-intron | ENST00000481256 | ENST00000552115 | LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972225 | + |
ORFfinder result based on the fusion transcript sequence of in-frame fusion genes. |
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) |
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 |
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Fusion Genomic Features for LRRK2-MON2 |
FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints. |
Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | 1-p | p (fusion gene breakpoint) |
LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972224 | + | 4.08E-06 | 0.99999595 |
LRRK2 | chr12 | 40637483 | + | MON2 | chr12 | 62972224 | + | 4.08E-06 | 0.99999595 |
Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page. |
Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page. |
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Fusion Protein Features for LRRK2-MON2 |
Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:40637483/:62972225) - 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. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
LRRK2 | MON2 |
FUNCTION: Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Independent of its kinase activity, inhibits the proteosomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29212815). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421}. | FUNCTION: Plays a role in regulating membrane trafficking of cargo proteins. Together with ATP9A and DOP1B, regulates SNX3 retromer-mediated endosomal sorting of WLS away from lysosomal degradation. {ECO:0000269|PubMed:30213940}. |
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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Fusion Gene Sequence for LRRK2-MON2 |
For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
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Fusion Gene PPI Analysis for LRRK2-MON2 |
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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Related Drugs for LRRK2-MON2 |
Drugs targeting genes involved in this fusion gene. (DrugBank Version 5.1.8 2021-05-08) |
Partner | Gene | UniProtAcc | DrugBank ID | Drug name | Drug activity | Drug type | Drug status |
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Related Diseases for LRRK2-MON2 |
Diseases associated with fusion partners. (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |