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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:AFAP1L2-RET (FusionGDB2 ID:HG84632TG5979) |
Fusion Gene Summary for AFAP1L2-RET |
Fusion gene summary |
Fusion gene information | Fusion gene name: AFAP1L2-RET | Fusion gene ID: hg84632tg5979 | Hgene | Tgene | Gene symbol | AFAP1L2 | RET | Gene ID | 84632 | 5979 |
Gene name | actin filament associated protein 1 like 2 | ret proto-oncogene | |
Synonyms | CTB-1144G6.4|KIAA1914|XB130 | CDHF12|CDHR16|HSCR1|MEN2A|MEN2B|MTC1|PTC|RET-ELE1 | |
Cytomap | ('AFAP1L2')('RET') 10q25.3 | 10q11.21 | |
Type of gene | protein-coding | protein-coding | |
Description | actin filament-associated protein 1-like 2AFAP1-like protein 2CTB-1144G6.6 | proto-oncogene tyrosine-protein kinase receptor RetRET receptor tyrosine kinasecadherin family member 12cadherin-related family member 16proto-oncogene c-Retrearranged during transfectionret proto-oncogene (multiple endocrine neoplasia and medullary | |
Modification date | 20200313 | 20200322 | |
UniProtAcc | . | P07949 | |
Ensembl transtripts involved in fusion gene | ENST00000304129, ENST00000369271, ENST00000491814, ENST00000545353, | ||
Fusion gene scores | * DoF score | 6 X 6 X 3=108 | 32 X 31 X 11=10912 |
# samples | 6 | 48 | |
** MAII score | log2(6/108*10)=-0.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(48/10912*10)=-4.50673733341565 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
Context | PubMed: AFAP1L2 [Title/Abstract] AND RET [Title/Abstract] AND fusion [Title/Abstract] | ||
Most frequent breakpoint | |||
Anticipated loss of major functional domain due to fusion event. |
* 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 | AFAP1L2 | GO:0006954 | inflammatory response | 17412687 |
Hgene | AFAP1L2 | GO:0007346 | regulation of mitotic cell cycle | 17412687 |
Hgene | AFAP1L2 | GO:0032675 | regulation of interleukin-6 production | 17412687 |
Hgene | AFAP1L2 | GO:0032757 | positive regulation of interleukin-8 production | 17412687 |
Hgene | AFAP1L2 | GO:0045742 | positive regulation of epidermal growth factor receptor signaling pathway | 17412687 |
Hgene | AFAP1L2 | GO:0045893 | positive regulation of transcription, DNA-templated | 17412687 |
Tgene | RET | GO:0030155 | regulation of cell adhesion | 21357690 |
Tgene | RET | GO:0030335 | positive regulation of cell migration | 20702524 |
Tgene | RET | GO:0033619 | membrane protein proteolysis | 21357690 |
Tgene | RET | GO:0033630 | positive regulation of cell adhesion mediated by integrin | 20702524 |
Tgene | RET | GO:0035860 | glial cell-derived neurotrophic factor receptor signaling pathway | 28953886 |
Tgene | RET | GO:0043410 | positive regulation of MAPK cascade | 28846099 |
Fusion gene information * 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 |
ChimerKB4 | . | . | AFAP1L2 | chr10 | 116100490 | - | RET | chr10 | 116100490 | + |
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Fusion Gene ORF analysis for AFAP1L2-RET |
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-intron | ENST00000304129 | ENST00000340058 | AFAP1L2 | chr10 | 116100490 | - | RET | chr10 | 116100490 | + |
intron-intron | ENST00000304129 | ENST00000355710 | AFAP1L2 | chr10 | 116100490 | - | RET | chr10 | 116100490 | + |
intron-intron | ENST00000369271 | ENST00000340058 | AFAP1L2 | chr10 | 116100490 | - | RET | chr10 | 116100490 | + |
intron-intron | ENST00000369271 | ENST00000355710 | AFAP1L2 | chr10 | 116100490 | - | RET | chr10 | 116100490 | + |
intron-intron | ENST00000491814 | ENST00000340058 | AFAP1L2 | chr10 | 116100490 | - | RET | chr10 | 116100490 | + |
intron-intron | ENST00000491814 | ENST00000355710 | AFAP1L2 | chr10 | 116100490 | - | RET | chr10 | 116100490 | + |
intron-intron | ENST00000545353 | ENST00000340058 | AFAP1L2 | chr10 | 116100490 | - | RET | chr10 | 116100490 | + |
intron-intron | ENST00000545353 | ENST00000355710 | AFAP1L2 | chr10 | 116100490 | - | RET | chr10 | 116100490 | + |
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 AFAP1L2-RET |
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) |
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Fusion Protein Features for AFAP1L2-RET |
Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:/:) - 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 |
. | RET |
FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}. | FUNCTION: Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways (PubMed:28846097, PubMed:28953886, PubMed:28846099). Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL (PubMed:28846099). {ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886}. |
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 AFAP1L2-RET |
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 AFAP1L2-RET |
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 AFAP1L2-RET |
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 |
Tgene | RET | P07949 | DB05294 | Vandetanib | Small molecule | Approved | |
Tgene | RET | P07949 | DB05294 | Vandetanib | Small molecule | Approved | |
Tgene | RET | P07949 | DB05294 | Vandetanib | Small molecule | Approved | |
Tgene | RET | P07949 | DB05294 | Vandetanib | Small molecule | Approved | |
Tgene | RET | P07949 | DB05294 | Vandetanib | Small molecule | Approved | |
Tgene | RET | P07949 | DB08896 | Regorafenib | Inhibitor | Small molecule | Approved |
Tgene | RET | P07949 | DB08896 | Regorafenib | Inhibitor | Small molecule | Approved |
Tgene | RET | P07949 | DB08896 | Regorafenib | Inhibitor | Small molecule | Approved |
Tgene | RET | P07949 | DB08896 | Regorafenib | Inhibitor | Small molecule | Approved |
Tgene | RET | P07949 | DB08896 | Regorafenib | Inhibitor | Small molecule | Approved |
Tgene | RET | P07949 | DB00398 | Sorafenib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB00398 | Sorafenib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB00398 | Sorafenib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB00398 | Sorafenib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB00398 | Sorafenib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08875 | Cabozantinib | Antagonist | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08875 | Cabozantinib | Antagonist | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08875 | Cabozantinib | Antagonist | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08875 | Cabozantinib | Antagonist | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08875 | Cabozantinib | Antagonist | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08901 | Ponatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08901 | Ponatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08901 | Ponatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08901 | Ponatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB08901 | Ponatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB09078 | Lenvatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB09078 | Lenvatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB09078 | Lenvatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB09078 | Lenvatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB09078 | Lenvatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB12010 | Fostamatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB12010 | Fostamatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB12010 | Fostamatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB12010 | Fostamatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB12010 | Fostamatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15685 | Selpercatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15685 | Selpercatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15685 | Selpercatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15685 | Selpercatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15685 | Selpercatinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15822 | Pralsetinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15822 | Pralsetinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15822 | Pralsetinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15822 | Pralsetinib | Inhibitor | Small molecule | Approved|Investigational |
Tgene | RET | P07949 | DB15822 | Pralsetinib | Inhibitor | Small molecule | Approved|Investigational |
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Related Diseases for AFAP1L2-RET |
Diseases associated with fusion partners. (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
Hgene | AFAP1L2 | C0007137 | Squamous cell carcinoma | 1 | CTD_human |
Tgene | C1833921 | Familial medullary thyroid carcinoma | 23 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT | |
Tgene | C3888239 | HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 1 | 16 | GENOMICS_ENGLAND;UNIPROT | |
Tgene | C0025268 | Multiple Endocrine Neoplasia Type 2a | 15 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT | |
Tgene | C1708353 | Hereditary Paraganglioma-Pheochromocytoma Syndrome | 12 | CLINGEN | |
Tgene | C0025269 | Multiple Endocrine Neoplasia Type 2b | 10 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT | |
Tgene | C0238463 | Papillary thyroid carcinoma | 3 | CTD_human;ORPHANET | |
Tgene | C1275808 | Congenital central hypoventilation | 3 | CTD_human;GENOMICS_ENGLAND;UNIPROT | |
Tgene | C1859049 | CCHS WITH HIRSCHSPRUNG DISEASE | 3 | CTD_human;ORPHANET | |
Tgene | C0009402 | Colorectal Carcinoma | 2 | CTD_human;UNIPROT | |
Tgene | C0009404 | Colorectal Neoplasms | 2 | CTD_human | |
Tgene | C0019569 | Hirschsprung Disease | 2 | CTD_human | |
Tgene | C0027662 | Multiple Endocrine Neoplasia | 2 | CTD_human;GENOMICS_ENGLAND | |
Tgene | C0085758 | Aganglionosis, Colonic | 2 | CTD_human | |
Tgene | C0266294 | Unilateral agenesis of kidney | 2 | ORPHANET | |
Tgene | C1257840 | Aganglionosis, Rectosigmoid Colon | 2 | CTD_human | |
Tgene | C3661523 | Congenital Intestinal Aganglionosis | 2 | CTD_human | |
Tgene | C0006413 | Burkitt Lymphoma | 1 | CTD_human | |
Tgene | C0031511 | Pheochromocytoma | 1 | CGI;CTD_human;GENOMICS_ENGLAND;UNIPROT | |
Tgene | C0038220 | Status Epilepticus | 1 | CTD_human | |
Tgene | C0040136 | Thyroid Neoplasm | 1 | CGI;CTD_human | |
Tgene | C0151468 | Thyroid Gland Follicular Adenoma | 1 | CTD_human | |
Tgene | C0206693 | Medullary carcinoma | 1 | CTD_human | |
Tgene | C0238462 | Medullary carcinoma of thyroid | 1 | CGI;CTD_human | |
Tgene | C0270823 | Petit mal status | 1 | CTD_human | |
Tgene | C0311335 | Grand Mal Status Epilepticus | 1 | CTD_human | |
Tgene | C0343640 | African Burkitt's lymphoma | 1 | CTD_human | |
Tgene | C0393734 | Complex Partial Status Epilepticus | 1 | CTD_human | |
Tgene | C0549473 | Thyroid carcinoma | 1 | CGI;CTD_human;UNIPROT | |
Tgene | C0740340 | Amyloidosis, Familial | 1 | CTD_human | |
Tgene | C0751522 | Status Epilepticus, Subclinical | 1 | CTD_human | |
Tgene | C0751523 | Non-Convulsive Status Epilepticus | 1 | CTD_human | |
Tgene | C0751524 | Simple Partial Status Epilepticus | 1 | CTD_human | |
Tgene | C1257877 | Pheochromocytoma, Extra-Adrenal | 1 | CTD_human | |
Tgene | C1609433 | Congenital absence of kidneys syndrome | 1 | CTD_human;GENOMICS_ENGLAND;ORPHANET | |
Tgene | C3501843 | Nonmedullary Thyroid Carcinoma | 1 | CTD_human | |
Tgene | C3501844 | Familial Nonmedullary Thyroid Cancer | 1 | CTD_human | |
Tgene | C4721444 | Burkitt Leukemia | 1 | CTD_human |