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	Kinase Fusion Gene Summary
	Kinase Fusion Gene Sample Information
	Kinase Fusion ORF Analysis
	Kinase Fusion Amino Acid Sequences
	Multiple Sequence Alignment of All Fusion Protein Isoforms
	Kinase Fusion Protein Functional Features
	Kinase Fusion Protein Structures
	Comparison of Fusion Protein Isoforms
	Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB
	pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.
	Ramachandran Plot of Kinase Fusion Protein Structure
	Potential Active Site Information
	Virtual Screening Results
	Kinase-Substrate Information
	Related Drugs with This Kinase Fusion Protein
	Related Disease with This Kinase Fusion Protein
	Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:RET_GOLGA5

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: RET_GOLGA5
	KinaseFusionDB ID: KFG5345
	FusionGDB2.0 ID: KFG5345
		Hgene	Tgene
	Gene symbol	RET	GOLGA5
	Gene ID	5979	440270
	Gene name	ret proto-oncogene
	Synonyms	CDHF12\|CDHR16\|HSCR1\|MEN2A\|MEN2B\|MTC1\|PTC\|RET-ELE1
	Cytomap	10q11.21
	Type of gene	protein-coding
	Description	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	20240416
	UniProtAcc	P07949	Q8TBA6
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000340058, ENST00000355710,	ENST00000163416, ENST00000355976,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: RET [Title/Abstract] AND GOLGA5 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	GOLGA5(93282767)-RET(43612030), # samples:2

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	RET	GO:0030155	regulation of cell adhesion	21357690
Hgene	RET	GO:0030335	positive regulation of cell migration	20702524
Hgene	RET	GO:0033619	membrane protein proteolysis	21357690
Hgene	RET	GO:0033630	positive regulation of cell adhesion mediated by integrin	20702524
Hgene	RET	GO:0035860	glial cell-derived neurotrophic factor receptor signaling pathway	24560924\|25242331\|28953886\|31535977
Hgene	RET	GO:0043410	positive regulation of MAPK cascade	28846099

Kinase Fusion gene breakpoints across RET (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Kinase Fusion gene breakpoints across GOLGA5 (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
ChimerKB3	.	RET	chr10	43610184	GOLGA5	chr14	93286052
COSMIC	2043279	RET	chr10	43610184	GOLGA5	chr14	93286053
COSMIC	2043280	RET	chr10	43610184	GOLGA5	chr14	93286053

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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)
ENST00000355710	ENST00000163416	RET	chr10	43610184	GOLGA5	chr14	93286053	3590	946
ENST00000355710	ENST00000163416	RET	chr10	43610184	GOLGA5	chr14	93286052	3590	946

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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

>ENST00000355710_ENST00000163416_RET_chr10_43610184_GOLGA5_chr14_93286053_length(amino acids)=946
MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE
DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR
PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP
TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR
NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS
TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR
CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC
DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILDMEAQQVN
EAESAREQLQDLHDQIAGQKASKQELETELERLKQEFHYIEEDLYRTKNTLQSRIKDRDEEIQKLRNQLTNKTLSNSSQSELENRLHQLT
ETLIQKQTMLESLSTEKNSLVFQLERLEQQMNSASGSSSNGSSINMSGIDNGEGTRLRNVPVLFNDTETNLAGMYGKVRKAASSIDQFSI

--------------------------------------------------------------

>ENST00000355710_ENST00000163416_RET_chr10_43610184_GOLGA5_chr14_93286052_length(amino acids)=946
MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE
DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR
PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP
TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR
NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS
TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR
CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC
DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILDMEAQQVN
EAESAREQLQDLHDQIAGQKASKQELETELERLKQEFHYIEEDLYRTKNTLQSRIKDRDEEIQKLRNQLTNKTLSNSSQSELENRLHQLT
ETLIQKQTMLESLSTEKNSLVFQLERLEQQMNSASGSSSNGSSINMSGIDNGEGTRLRNVPVLFNDTETNLAGMYGKVRKAASSIDQFSI

--------------------------------------------------------------

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/chr10:93282767/chr14:43612030)
- 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 P07949	GOLGA5 Q8TBA6
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}.	FUNCTION: Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport. {ECO:0000269\|PubMed:12538640, ECO:0000269\|PubMed:15718469}.

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
download page
* 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).

712712712712

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

Hgene

RET

43610184

GOLGA5

93286052

ENST00000355710

168_272

1073

Domain

Note=Cadherin;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00043

Hgene

RET

43610184

GOLGA5

93286052

ENST00000355710

168_272

1115

Domain

Note=Cadherin;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00043

Hgene

RET

43610184

GOLGA5

93286053

ENST00000355710

168_272

1073

Domain

Note=Cadherin;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00043

Hgene

RET

43610184

GOLGA5

93286053

ENST00000355710

168_272

1115

Domain

Note=Cadherin;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00043

- 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

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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 >>>227_RET_GOLGA5	ENST00000355710	ENST00000163416	RET	chr10	43610184	GOLGA5	chr14	93286052	MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILDMEAQQVN EAESAREQLQDLHDQIAGQKASKQELETELERLKQEFHYIEEDLYRTKNTLQSRIKDRDEEIQKLRNQLTNKTLSNSSQSELENRLHQLT ETLIQKQTMLESLSTEKNSLVFQLERLEQQMNSASGSSSNGSSINMSGIDNGEGTRLRNVPVLFNDTETNLAGMYGKVRKAASSIDQFSI	946
3D view using mol* of 227_RET_GOLGA5

PDB file >>>HKFP_329_RET_GOLGA5	ENST00000355710	ENST00000163416	RET	chr10	43610184	GOLGA5	chr14	93286053	MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILDMEAQQVN EAESAREQLQDLHDQIAGQKASKQELETELERLKQEFHYIEEDLYRTKNTLQSRIKDRDEEIQKLRNQLTNKTLSNSSQSELENRLHQLT ETLIQKQTMLESLSTEKNSLVFQLERLEQQMNSASGSSSNGSSINMSGIDNGEGTRLRNVPVLFNDTETNLAGMYGKVRKAASSIDQFSI	946_RET_GOLGA5
PDB file >>>HKFP_330_RET_GOLGA5	ENST00000355710	ENST00000163416	RET	chr10	43610184	GOLGA5	chr14	93286052	MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILDMEAQQVN EAESAREQLQDLHDQIAGQKASKQELETELERLKQEFHYIEEDLYRTKNTLQSRIKDRDEEIQKLRNQLTNKTLSNSSQSELENRLHQLT ETLIQKQTMLESLSTEKNSLVFQLERLEQQMNSASGSSSNGSSINMSGIDNGEGTRLRNVPVLFNDTETNLAGMYGKVRKAASSIDQFSI	946_RET_GOLGA5

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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

RET_GOLGA5 does not have any known PDB structures.

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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.

227_RET_GOLGA5.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

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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.

227_RET_GOLGA5_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
227_RET_GOLGA5-DOCK_HTVS_1-001	Erlotinib	10000.0	10000.0	12.3779
227_RET_GOLGA5-DOCK_HTVS_1-001	Tofacitinib	10000.0	10000.0	15.2283
227_RET_GOLGA5-DOCK_HTVS_1-001	Tofacitinib	10000.0	10000.0	15.2283
227_RET_GOLGA5-DOCK_HTVS_1-001	Binimetinib	10000.0	10000.0	9.6528
227_RET_GOLGA5-DOCK_HTVS_1-001	Binimetinib	10000.0	10000.0	9.6528
227_RET_GOLGA5-DOCK_HTVS_1-001	Crizotinib	10000.5	10000.0	28.1426
227_RET_GOLGA5-DOCK_HTVS_1-001	Crizotinib	10000.5	10000.0	28.1426
227_RET_GOLGA5-DOCK_HTVS_1-001	Asciminib	10000.5	10000.0	24.7277
227_RET_GOLGA5-DOCK_HTVS_1-001	Asciminib	10000.5	10000.0	36.2928
227_RET_GOLGA5-DOCK_HTVS_1-001	Asciminib	10000.5	10000.0	26.7426
227_RET_GOLGA5-DOCK_HTVS_1-001	Afatinib	10001.8	10000.0	30.7559
227_RET_GOLGA5-DOCK_HTVS_1-001	Afatinib	10001.8	10000.0	30.7559
227_RET_GOLGA5-DOCK_HTVS_1-001	Afatinib	10001.8	10000.0	30.7559
227_RET_GOLGA5-DOCK_HTVS_1-001	Sirolimus
227_RET_GOLGA5-DOCK_HTVS_1-001	Sirolimus
227_RET_GOLGA5-DOCK_HTVS_1-001	Sirolimus
227_RET_GOLGA5-DOCK_HTVS_1-001	Sirolimus
227_RET_GOLGA5-DOCK_HTVS_1-001	Sirolimus
227_RET_GOLGA5-DOCK_HTVS_1-001	Sirolimus
227_RET_GOLGA5-DOCK_HTVS_1-001	Sirolimus

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Kinase-Substrate Information of RET_GOLGA5

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
RET	Q15300	human	STAT3	P40763	Y705	DPGsAAPyLktKFIC
RET	Q15300	human	RET	Q15300	Y586	TWIENKLyGRISHAF
RET	P07949	human	RET	P07949	Y981	DNCSEEMyRLMLQCW	PK_Tyr_Ser-Thr
RET	P07949	human	PTK2	Q05397	Y925	DRsNDkVyENVtGLV	Focal_AT
RET	P07949	human	RET	P07949	Y1090	TNTGFPRyPNDSVyA
RET	P07949	human	ATF4	P18848	T107	LGIDDLEtMPDDLLt
RET	P07949	human	PTK2	Q05397	Y577	yMEDstyyKAsKGKL	PK_Tyr_Ser-Thr
RET	P07949	human	ATF4	P18848	T115	MPDDLLttLDDtCDL
RET	P07949	human	MAPK9	P45984	Y185	tNFMMtPyVVtRYYR	Pkinase
RET	P07949	human	RET	P07949	Y1096	RyPNDSVyANWMLSP
RET	P07949	human	MAPK8	P45983	Y185	tsFMMtPyVVtRYYR	Pkinase
RET	P07949	human	PIK3R1	P27986	Y203	PVIPAAVySEMIsLA	RhoGAP
RET	P07949	human	RET	P07949	Y826	SRKVGPGyLGSGGSR	PK_Tyr_Ser-Thr
RET	P07949	human	RET	P07949	Y1015	MMVKRRDyLDLAAST
RET	P07949	human	PDPK1	O15530	Y9	ARTTSQLyDAVPIQS
RET	P07949	human	ATF4	P18848	T114	tMPDDLLttLDDtCD
RET	P07949	human	DOK1	Q99704	Y398	ARVkEEGyELPyNPA
RET	P07949	human	RET	P07949	Y809	LIVEyAKyGSLRGFL	PK_Tyr_Ser-Thr
RET	P07949	human	PTK2	Q05397	Y861	PIGNQHIyQPVGKPD
RET	P07949	human	ATF4	P18848	T119	LLttLDDtCDLFAPL
RET	P07949	human	RET	P07949	Y1029	TPSDSLIyDDGLSEE
RET	P07949	human	RET	P07949	Y687	AQAFPVsysSSGARR
RET	P07949	human	PLCG1	P19174	Y783	EGRNPGFyVEANPMP
RET	P07949	human	MAPK3	P27361	T202	HDHtGFLtEyVAtRW	Pkinase
RET	P07949	human	AFAP1L2	Q8N4X5	Y54	SSSsDEEyIyMNKVt
RET	P07949	human	AKT1	P31749	Y315	tFCGtPEyLAPEVLE	Pkinase
RET	P07949	human	RET	P07949	Y806	PLLLIVEyAKyGSLR	PK_Tyr_Ser-Thr
RET	P07949	human	RET	P07949	Y900	FGLSRDVyEEDsyVK	PK_Tyr_Ser-Thr
RET	P07949	human	MAPK1	P28482	Y187	HtGFLtEyVAtRWyr	Pkinase
RET	P07949	human	RET	P07949	Y905	DVyEEDsyVKRsQGR	PK_Tyr_Ser-Thr
RET	P07949	human	PTK2	Q05397	Y576	RyMEDstyyKAsKGK	PK_Tyr_Ser-Thr
RET	P07949	human	MAPK3	P27361	Y204	HtGFLtEyVAtRWyr	Pkinase
RET	P07949	human	RET	P07949	Y1062	TWIENkLyGMsDPNW
RET	P07949	human	MAPK14	Q16539	Y182	tDDEMtGyVAtRWYR	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
RET	ID	Description	0.00e+00
RET	GO:0071276	cellular response to cadmium ion	8.65e-08
RET	GO:0070849	response to epidermal growth factor	1.02e-07
RET	GO:0038127	ERBB signaling pathway	1.02e-07
RET	GO:0043434	response to peptide hormone	1.02e-07
RET	GO:0048009	insulin-like growth factor receptor signaling pathway	1.02e-07
RET	GO:0046686	response to cadmium ion	1.64e-07
RET	GO:0018105	peptidyl-serine phosphorylation	2.35e-07
RET	GO:0018209	peptidyl-serine modification	2.58e-07
RET	GO:0071375	cellular response to peptide hormone stimulus	2.58e-07
RET	GO:0071248	cellular response to metal ion	7.74e-07
RET	GO:1901653	cellular response to peptide	7.74e-07
RET	GO:0071241	cellular response to inorganic substance	1.52e-06
RET	GO:0007173	epidermal growth factor receptor signaling pathway	1.57e-06
RET	GO:0060416	response to growth hormone	1.79e-06
RET	GO:0034599	cellular response to oxidative stress	2.31e-06
RET	GO:0008286	insulin receptor signaling pathway	2.80e-06
RET	GO:0032868	response to insulin	2.80e-06
RET	GO:0002764	immune response-regulating signaling pathway	3.49e-06
RET	GO:0043491	phosphatidylinositol 3-kinase/protein kinase B signal transduction	3.92e-06
RET	GO:0034198	cellular response to amino acid starvation	4.22e-06
RET	GO:1990928	response to amino acid starvation	5.08e-06
RET	GO:0009411	response to UV	5.10e-06
RET	GO:0038093	Fc receptor signaling pathway	5.10e-06
RET	GO:0062197	cellular response to chemical stress	5.10e-06
RET	GO:0034614	cellular response to reactive oxygen species	5.10e-06
RET	GO:0031663	lipopolysaccharide-mediated signaling pathway	5.49e-06
RET	GO:0061517	macrophage proliferation	5.72e-06
RET	GO:0002768	immune response-regulating cell surface receptor signaling pathway	7.56e-06
RET	GO:0010038	response to metal ion	9.07e-06
RET	GO:0050900	leukocyte migration	1.56e-05
RET	GO:0006979	response to oxidative stress	1.59e-05
RET	GO:0010759	positive regulation of macrophage chemotaxis	1.59e-05
RET	GO:0000302	response to reactive oxygen species	1.59e-05
RET	GO:0032869	cellular response to insulin stimulus	1.59e-05
RET	GO:0071674	mononuclear cell migration	1.59e-05
RET	GO:0051347	positive regulation of transferase activity	1.69e-05
RET	GO:0034764	positive regulation of transmembrane transport	1.90e-05
RET	GO:0071222	cellular response to lipopolysaccharide	2.26e-05
RET	GO:0001503	ossification	2.28e-05
RET	GO:0002685	regulation of leukocyte migration	2.28e-05
RET	GO:0051403	stress-activated MAPK cascade	2.28e-05
RET	GO:0031098	stress-activated protein kinase signaling cascade	2.63e-05
RET	GO:0071219	cellular response to molecule of bacterial origin	2.63e-05
RET	GO:0038095	Fc-epsilon receptor signaling pathway	2.75e-05
RET	GO:0060396	growth hormone receptor signaling pathway	2.75e-05
RET	GO:0018107	peptidyl-threonine phosphorylation	2.76e-05
RET	GO:0048863	stem cell differentiation	2.76e-05
RET	GO:0002757	immune response-activating signaling pathway	2.76e-05
RET	GO:0071378	cellular response to growth hormone stimulus	2.79e-05

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Related Drugs to RET_GOLGA5

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 RET-GOLGA5 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 RET_GOLGA5

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
Hgene	RET	C1833921	Familial medullary thyroid carcinoma	23	CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Hgene	RET	C3888239	HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 1	16	GENOMICS_ENGLAND;UNIPROT
Hgene	RET	C0025268	Multiple Endocrine Neoplasia Type 2a	15	CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Hgene	RET	C1708353	Hereditary Paraganglioma-Pheochromocytoma Syndrome	12	CLINGEN
Hgene	RET	C0025269	Multiple Endocrine Neoplasia Type 2b	10	CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Hgene	RET	C0238463	Papillary thyroid carcinoma	3	CTD_human;ORPHANET
Hgene	RET	C1275808	Congenital central hypoventilation	3	CTD_human;GENOMICS_ENGLAND;UNIPROT
Hgene	RET	C1859049	CCHS WITH HIRSCHSPRUNG DISEASE	3	CTD_human;ORPHANET
Hgene	RET	C0009402	Colorectal Carcinoma	2	CTD_human;UNIPROT
Hgene	RET	C0009404	Colorectal Neoplasms	2	CTD_human
Hgene	RET	C0019569	Hirschsprung Disease	2	CTD_human
Hgene	RET	C0027662	Multiple Endocrine Neoplasia	2	CTD_human;GENOMICS_ENGLAND
Hgene	RET	C0085758	Aganglionosis, Colonic	2	CTD_human
Hgene	RET	C0266294	Unilateral agenesis of kidney	2	ORPHANET
Hgene	RET	C1257840	Aganglionosis, Rectosigmoid Colon	2	CTD_human
Hgene	RET	C3661523	Congenital Intestinal Aganglionosis	2	CTD_human
Tgene	GOLGA5	C0238463	Papillary thyroid carcinoma	2	ORPHANET

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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