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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:AFAP1L2-RET (FusionGDB2 ID:HG84632TG5979)

Fusion Gene Summary for AFAP1L2-RET

check button Fusion gene summary
Fusion gene informationFusion gene name: AFAP1L2-RET
Fusion gene ID: hg84632tg5979
HgeneTgene
Gene symbol

AFAP1L2

RET

Gene ID

84632

5979

Gene nameactin filament associated protein 1 like 2ret proto-oncogene
SynonymsCTB-1144G6.4|KIAA1914|XB130CDHF12|CDHR16|HSCR1|MEN2A|MEN2B|MTC1|PTC|RET-ELE1
Cytomap('AFAP1L2')('RET')

10q25.3

10q11.21

Type of geneprotein-codingprotein-coding
Descriptionactin filament-associated protein 1-like 2AFAP1-like protein 2CTB-1144G6.6proto-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 date2020031320200322
UniProtAcc.

P07949

Ensembl transtripts involved in fusion geneENST00000304129, ENST00000369271, 
ENST00000491814, ENST00000545353, 
Fusion gene scores* DoF score6 X 6 X 3=10832 X 31 X 11=10912
# samples 648
** MAII scorelog2(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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneAFAP1L2

GO:0006954

inflammatory response

17412687

HgeneAFAP1L2

GO:0007346

regulation of mitotic cell cycle

17412687

HgeneAFAP1L2

GO:0032675

regulation of interleukin-6 production

17412687

HgeneAFAP1L2

GO:0032757

positive regulation of interleukin-8 production

17412687

HgeneAFAP1L2

GO:0045742

positive regulation of epidermal growth factor receptor signaling pathway

17412687

HgeneAFAP1L2

GO:0045893

positive regulation of transcription, DNA-templated

17412687

TgeneRET

GO:0030155

regulation of cell adhesion

21357690

TgeneRET

GO:0030335

positive regulation of cell migration

20702524

TgeneRET

GO:0033619

membrane protein proteolysis

21357690

TgeneRET

GO:0033630

positive regulation of cell adhesion mediated by integrin

20702524

TgeneRET

GO:0035860

glial cell-derived neurotrophic factor receptor signaling pathway

28953886

TgeneRET

GO:0043410

positive regulation of MAPK cascade

28846099



check button 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerKB4..AFAP1L2chr10

116100490

-RETchr10

116100490

+


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Fusion Gene ORF analysis for AFAP1L2-RET

check button 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.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
intron-intronENST00000304129ENST00000340058AFAP1L2chr10

116100490

-RETchr10

116100490

+
intron-intronENST00000304129ENST00000355710AFAP1L2chr10

116100490

-RETchr10

116100490

+
intron-intronENST00000369271ENST00000340058AFAP1L2chr10

116100490

-RETchr10

116100490

+
intron-intronENST00000369271ENST00000355710AFAP1L2chr10

116100490

-RETchr10

116100490

+
intron-intronENST00000491814ENST00000340058AFAP1L2chr10

116100490

-RETchr10

116100490

+
intron-intronENST00000491814ENST00000355710AFAP1L2chr10

116100490

-RETchr10

116100490

+
intron-intronENST00000545353ENST00000340058AFAP1L2chr10

116100490

-RETchr10

116100490

+
intron-intronENST00000545353ENST00000355710AFAP1L2chr10

116100490

-RETchr10

116100490

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)

check buttonDeepORF 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.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score

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Fusion Genomic Features for AFAP1L2-RET


check buttonFusionAI 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.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)


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Fusion Protein Features for AFAP1L2-RET


check button 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
.RET

P07949

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}.

check buttonRetention 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

download page


* 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.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for AFAP1L2-RET


check button 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


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for AFAP1L2-RET


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational

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Related Diseases for AFAP1L2-RET


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneAFAP1L2C0007137Squamous cell carcinoma1CTD_human
TgeneC1833921Familial medullary thyroid carcinoma23CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC3888239HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 116GENOMICS_ENGLAND;UNIPROT
TgeneC0025268Multiple Endocrine Neoplasia Type 2a15CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC1708353Hereditary Paraganglioma-Pheochromocytoma Syndrome12CLINGEN
TgeneC0025269Multiple Endocrine Neoplasia Type 2b10CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC0238463Papillary thyroid carcinoma3CTD_human;ORPHANET
TgeneC1275808Congenital central hypoventilation3CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneC1859049CCHS WITH HIRSCHSPRUNG DISEASE3CTD_human;ORPHANET
TgeneC0009402Colorectal Carcinoma2CTD_human;UNIPROT
TgeneC0009404Colorectal Neoplasms2CTD_human
TgeneC0019569Hirschsprung Disease2CTD_human
TgeneC0027662Multiple Endocrine Neoplasia2CTD_human;GENOMICS_ENGLAND
TgeneC0085758Aganglionosis, Colonic2CTD_human
TgeneC0266294Unilateral agenesis of kidney2ORPHANET
TgeneC1257840Aganglionosis, Rectosigmoid Colon2CTD_human
TgeneC3661523Congenital Intestinal Aganglionosis2CTD_human
TgeneC0006413Burkitt Lymphoma1CTD_human
TgeneC0031511Pheochromocytoma1CGI;CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneC0038220Status Epilepticus1CTD_human
TgeneC0040136Thyroid Neoplasm1CGI;CTD_human
TgeneC0151468Thyroid Gland Follicular Adenoma1CTD_human
TgeneC0206693Medullary carcinoma1CTD_human
TgeneC0238462Medullary carcinoma of thyroid1CGI;CTD_human
TgeneC0270823Petit mal status1CTD_human
TgeneC0311335Grand Mal Status Epilepticus1CTD_human
TgeneC0343640African Burkitt's lymphoma1CTD_human
TgeneC0393734Complex Partial Status Epilepticus1CTD_human
TgeneC0549473Thyroid carcinoma1CGI;CTD_human;UNIPROT
TgeneC0740340Amyloidosis, Familial1CTD_human
TgeneC0751522Status Epilepticus, Subclinical1CTD_human
TgeneC0751523Non-Convulsive Status Epilepticus1CTD_human
TgeneC0751524Simple Partial Status Epilepticus1CTD_human
TgeneC1257877Pheochromocytoma, Extra-Adrenal1CTD_human
TgeneC1609433Congenital absence of kidneys syndrome1CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneC3501843Nonmedullary Thyroid Carcinoma1CTD_human
TgeneC3501844Familial Nonmedullary Thyroid Cancer1CTD_human
TgeneC4721444Burkitt Leukemia1CTD_human