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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:MET_TFG

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: MET_TFG
	KinaseFusionDB ID: KFG3836
	FusionGDB2.0 ID: KFG3836
		Hgene	Tgene
	Gene symbol	MET	TFG
	Gene ID	8731	10342
	Gene name	RNA guanine-7 methyltransferase	trafficking from ER to golgi regulator
	Synonyms	CMT1\|CMT1c\|MET\|Met\|N7-MTase\|RG7MT1\|cm1p\|hCMT1\|hMet	HMSNP\|SPG57\|TF6\|TRKT3
	Cytomap	18p11.21	3q12.2
	Type of gene	protein-coding	protein-coding
	Description	mRNA cap guanine-N7 methyltransferaseRNA (guanine-7-) methyltransferasehcm1pmRNA (guanine-7-)methyltransferasemRNA (guanine-N(7)-)-methyltransferasemRNA cap methyltransferase	protein TFGTRK-fusedTRK-fused gene proteinTRKT3 oncogene
	Modification date	20240403	20240407
	UniProtAcc	Q9H1A3	Q92734
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000318493, ENST00000397752, ENST00000436117, ENST00000495962, ENST00000539704,	ENST00000481203, ENST00000240851, ENST00000418917, ENST00000476228, ENST00000490574,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: MET [Title/Abstract] AND TFG [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	MET(116412043)-TFG(100455420), # samples:3 TFG(100451516)-MET(116414935), # samples:3

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	MET	GO:0006370	7-methylguanosine mRNA capping	27422871

Kinase Fusion gene breakpoints across MET (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 TFG (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
ChimerDB4	TCGA-FK-A3S3-01A	MET	chr7	116412043	TFG	chr3	100455420
ChimerDB4	TCGA-FK-A3S3	MET	chr7	116412043	TFG	chr3	100455419

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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)
ENST00000397752	ENST00000418917	MET	chr7	116412043	TFG	chr3	100455420	4250	1212
ENST00000397752	ENST00000418917	MET	chr7	116412043	TFG	chr3	100455419	4250	1212

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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

>ENST00000397752_ENST00000418917_MET_chr7_116412043_TFG_chr3_100455420_length(amino acids)=1212
MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVL
EHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL
GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLD
AQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS
AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDL
TIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW
CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAM
NKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF
AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLN
LQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL
LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVS
PTTEMVSNESVDYRATFPEGPPSAPAEDRSGTPDSIASSSSAAHPPGVQPQQPPYTGAQTQAGQMYQQYQQQAGYGAQQPQAPPQQPQQY
GIQYSASYSQQTGPQQPQQFQGYGQQPTSQAPAPAFSGQPQQLPAQPPQQYQASNYPAQTYTAQTSQPTNYTVAPASQPGMAPSQPGAYQ

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

>ENST00000397752_ENST00000418917_MET_chr7_116412043_TFG_chr3_100455419_length(amino acids)=1212
MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVL
EHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL
GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLD
AQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS
AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDL
TIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW
CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAM
NKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF
AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLN
LQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL
LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVS
PTTEMVSNESVDYRATFPEGPPSAPAEDRSGTPDSIASSSSAAHPPGVQPQQPPYTGAQTQAGQMYQQYQQQAGYGAQQPQAPPQQPQQY
GIQYSASYSQQTGPQQPQQFQGYGQQPTSQAPAPAFSGQPQQLPAQPPQQYQASNYPAQTYTAQTSQPTNYTVAPASQPGMAPSQPGAYQ

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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/chr7:116412043/chr3:100455420)
- 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
MET Q9H1A3	TFG Q92734
FUNCTION: Protein-histidine N-methyltransferase that specifically catalyzes 1-methylhistidine (pros-methylhistidine) methylation of target proteins (PubMed:33563959, PubMed:34562450). Mediates methylation of proteins with a His-x-His (HxH) motif (where 'x' is preferably a small amino acid) (PubMed:33563959). Catalyzes methylation of target proteins such as S100A9, NDUFB3, SLC39A5, SLC39A7, ARMC6 and DNAJB12; 1-methylhistidine modification may affect the binding of zinc and other metals to its target proteins (PubMed:33563959, PubMed:34562450). Constitutes the main methyltransferase for the 1-methylhistidine modification in cell (PubMed:33563959). {ECO:0000269\|PubMed:33563959, ECO:0000269\|PubMed:34562450}.	FUNCTION: Plays a role in the normal dynamic function of the endoplasmic reticulum (ER) and its associated microtubules (PubMed:23479643, PubMed:27813252). Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:21478858). {ECO:0000269\|PubMed:21478858, ECO:0000269\|PubMed:23479643, ECO:0000269\|PubMed:27813252}.

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).

1009102710091027100910271009102710091027100910271009102710091027

Partner	Hgeneene	Hbp	Tgeneene	Tbp	ENST	BPexon	TotalExon	Protein feature loci	BPloci	TotalLen	Feature	Note
Hgene	MET	116412043	TFG	100455419	ENST00000397752	14	21	563_655	1	1391	Domain	Note=IPT/TIG 1
Hgene	MET	116412043	TFG	100455419	ENST00000397752	14	21	563_655	1	1409	Domain	Note=IPT/TIG 1
Hgene	MET	116412043	TFG	100455420	ENST00000397752	14	21	563_655	1	1391	Domain	Note=IPT/TIG 1
Hgene	MET	116412043	TFG	100455420	ENST00000397752	14	21	563_655	1	1409	Domain	Note=IPT/TIG 1
Hgene	MET	116412043	TFG	100455419	ENST00000397752	14	21	657_739	1	1391	Domain	Note=IPT/TIG 2
Hgene	MET	116412043	TFG	100455419	ENST00000397752	14	21	657_739	1	1409	Domain	Note=IPT/TIG 2
Hgene	MET	116412043	TFG	100455420	ENST00000397752	14	21	657_739	1	1391	Domain	Note=IPT/TIG 2
Hgene	MET	116412043	TFG	100455420	ENST00000397752	14	21	657_739	1	1409	Domain	Note=IPT/TIG 2
Hgene	MET	116412043	TFG	100455419	ENST00000397752	14	21	742_836	1	1391	Domain	Note=IPT/TIG 3
Hgene	MET	116412043	TFG	100455419	ENST00000397752	14	21	742_836	1	1409	Domain	Note=IPT/TIG 3
Hgene	MET	116412043	TFG	100455420	ENST00000397752	14	21	742_836	1	1391	Domain	Note=IPT/TIG 3
Hgene	MET	116412043	TFG	100455420	ENST00000397752	14	21	742_836	1	1409	Domain	Note=IPT/TIG 3
Hgene	MET	116412043	TFG	100455419	ENST00000397752	14	21	27_515	1	1391	Domain	Note=Sema;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00352
Hgene	MET	116412043	TFG	100455419	ENST00000397752	14	21	27_515	1	1409	Domain	Note=Sema;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00352
Hgene	MET	116412043	TFG	100455420	ENST00000397752	14	21	27_515	1	1391	Domain	Note=Sema;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00352
Hgene	MET	116412043	TFG	100455420	ENST00000397752	14	21	27_515	1	1409	Domain	Note=Sema;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00352

- 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 >>>169_MET_TFG	ENST00000397752	ENST00000418917	MET	chr7	116412043	TFG	chr3	100455419	MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVL EHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLD AQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDL TIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAM NKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLN LQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVS PTTEMVSNESVDYRATFPEGPPSAPAEDRSGTPDSIASSSSAAHPPGVQPQQPPYTGAQTQAGQMYQQYQQQAGYGAQQPQAPPQQPQQY GIQYSASYSQQTGPQQPQQFQGYGQQPTSQAPAPAFSGQPQQLPAQPPQQYQASNYPAQTYTAQTSQPTNYTVAPASQPGMAPSQPGAYQ	1212
3D view using mol* of 169_MET_TFG

PDB file >>>HKFP_247_MET_TFG	ENST00000397752	ENST00000418917	MET	chr7	116412043	TFG	chr3	100455420	MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVL EHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLD AQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDL TIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAM NKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLN LQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVS PTTEMVSNESVDYRATFPEGPPSAPAEDRSGTPDSIASSSSAAHPPGVQPQQPPYTGAQTQAGQMYQQYQQQAGYGAQQPQAPPQQPQQY GIQYSASYSQQTGPQQPQQFQGYGQQPTSQAPAPAFSGQPQQLPAQPPQQYQASNYPAQTYTAQTSQPTNYTVAPASQPGMAPSQPGAYQ	1212_MET_TFG
PDB file >>>HKFP_248_MET_TFG	ENST00000397752	ENST00000418917	MET	chr7	116412043	TFG	chr3	100455419	MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVL EHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLD AQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDL TIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAM NKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLN LQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVS PTTEMVSNESVDYRATFPEGPPSAPAEDRSGTPDSIASSSSAAHPPGVQPQQPPYTGAQTQAGQMYQQYQQQAGYGAQQPQAPPQQPQQY GIQYSASYSQQTGPQQPQQFQGYGQQPTSQAPAPAFSGQPQQLPAQPPQQYQASNYPAQTYTAQTSQPTNYTVAPASQPGMAPSQPGAYQ	1212_MET_TFG

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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

MET_TFG 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.

169_MET_TFG.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.

169_MET_TFG_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
169_MET_TFG-DOCK_HTVS_1-001	Tepotinib	-7.141789999999999	-7.1428899999999995	-57.2009
169_MET_TFG-DOCK_HTVS_1-001	Everolimus	-6.82707	-6.828469999999999	-51.7874
169_MET_TFG-DOCK_HTVS_1-001	Mobocertinib	-6.640910000000001	-6.648610000000001	-66.3634
169_MET_TFG-DOCK_HTVS_1-001	Everolimus	-6.631189999999999	-6.6325899999999995	-61.9944
169_MET_TFG-DOCK_HTVS_1-001	Everolimus	-6.60716	-6.608560000000001	-53.9441
169_MET_TFG-DOCK_HTVS_1-001	Temsirolimus	-6.44602	-6.44742	-49.9161
169_MET_TFG-DOCK_HTVS_1-001	Temsirolimus	-6.17204	-6.17344	-54.3719
169_MET_TFG-DOCK_HTVS_1-001	Larotrectinib	-6.14275	-6.14275	-45.9442
169_MET_TFG-DOCK_HTVS_1-001	Trametinib	-6.0381599999999995	-6.0381599999999995	-47.417
169_MET_TFG-DOCK_HTVS_1-001	Lapatinib	-6.02355	-6.11235	-62.4881
169_MET_TFG-DOCK_HTVS_1-001	Nilotinib	-5.99044	-6.91524	-55.5456
169_MET_TFG-DOCK_HTVS_1-001	Nilotinib	-5.99044	-6.91524	-55.5456
169_MET_TFG-DOCK_HTVS_1-001	Everolimus	-5.94487	-5.946269999999999	-53.0965
169_MET_TFG-DOCK_HTVS_1-001	Temsirolimus	-5.94302	-5.94442	-55.2467
169_MET_TFG-DOCK_HTVS_1-001	Temsirolimus	-5.932259999999999	-5.93366	-53.433
169_MET_TFG-DOCK_HTVS_1-001	Lapatinib	-5.92518	-6.01398	-58.4314
169_MET_TFG-DOCK_HTVS_1-001	Temsirolimus	-5.91164	-5.9130400000000005	-53.556999999999995
169_MET_TFG-DOCK_HTVS_1-001	Cobimetinib	-5.905480000000001	-5.90828	-42.7542
169_MET_TFG-DOCK_HTVS_1-001	Encorafenib	-5.8719	-6.2604	-56.6778
169_MET_TFG-DOCK_HTVS_1-001	Encorafenib	-5.86341	-6.25191	-56.7528

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Kinase-Substrate Information of MET_TFG

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
MET	P08581	human	MST1R	Q04912	Y1353	SALLGDHyVQLPATy
MET	P08581	human	FIS1	Q9Y3D6	Y38	sKSTQFEyAWCLVRS	Fis1_TPR_N
MET	P08581	human	IRS1	P35568	Y612	tLHtDDGyMPMsPGV
MET	P08581	human	PTK2	Q05397	Y925	DRsNDkVyENVtGLV	Focal_AT
MET	P08581	human	MET	P08581	Y1349	stFIGEHyVHVNAty
MET	P08581	human	MET	P08581	Y1365	NVKCVAPyPsLLssE
MET	P08581	human	IRS1	P35568	Y896	EPKsPGEyVNIEFGS
MET	P08581	human	PTK2	Q05397	Y577	yMEDstyyKAsKGKL	PK_Tyr_Ser-Thr
MET	P08581	human	RHOA	P61586	Y42	VPTVFENyVADIEVD	Ras
MET	P08581	human	MST1R	Q04912	Y1360	yVQLPATyMNLGPST
MET	P08581	human	MST1R	Q04912	Y1238	RDILDREyysVQQHR	PK_Tyr_Ser-Thr
MET	P08581	human	IQGAP1	P46940	Y1510	LVkLQQtyAALNskA	RasGAP_C
MET	P08581	human	PTK2	Q05397	Y407	IIDEEDtytMPSTRD
MET	P08581	human	MET	P08581	Y1230	FGLARDMyDkEyysV	PK_Tyr_Ser-Thr
MET	P08581	human	PARP1	P09874	Y907	MVSKSANyCHTSQGD	PARP
MET	P08581	human	SHC1	P29353	Y427	ELFDDPsyVNVQNLD
MET	P08581	human	MET	P08581	Y1356	yVHVNAtyVNVKCVA
MET	P08581	human	PTK2	Q05397	Y5	___MAAAyLDPNLNH
MET	P08581	human	PTK2	Q05397	Y397	sVsEtDDyAEIIDEE
MET	P08581	human	PTK2	Q05397	Y861	PIGNQHIyQPVGKPD
MET	P08581	human	PBK	Q96KB5	Y74	NPICNDHyRsVyQkR	Pkinase
MET	P08581	human	PTK2	Q05397	Y194	ALEKKSNyEVLEkDV	FERM_M
MET	P08581	human	MET	P08581	Y1234	RDMyDkEyysVHNkt	PK_Tyr_Ser-Thr
MET	P08581	human	PTK2	Q05397	Y576	RyMEDstyyKAsKGK	PK_Tyr_Ser-Thr
MET	P08581	human	INSR	P06213	Y1185	FGMTRDIyEtDyyRk	PK_Tyr_Ser-Thr
MET	P08581	human	MET	P08581	Y1235	DMyDkEyysVHNktG	PK_Tyr_Ser-Thr
MET	P08581	human	GSK3B	P49841	Y56	DRPQEVSyTDTKVIG	Pkinase
MET	P08581	human	MST1R	Q04912	Y1239	DILDREyysVQQHRH	PK_Tyr_Ser-Thr

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
MET	ID	Description	0.00e+00
MET	GO:0033674	positive regulation of kinase activity	4.44e-07
MET	GO:0051347	positive regulation of transferase activity	9.31e-07
MET	GO:0071375	cellular response to peptide hormone stimulus	5.90e-06
MET	GO:1901653	cellular response to peptide	1.35e-05
MET	GO:0032869	cellular response to insulin stimulus	2.06e-05
MET	GO:0043434	response to peptide hormone	2.06e-05
MET	GO:0032868	response to insulin	6.57e-05
MET	GO:0045860	positive regulation of protein kinase activity	7.26e-05
MET	GO:0008286	insulin receptor signaling pathway	8.83e-05
MET	GO:0005979	regulation of glycogen biosynthetic process	8.83e-05
MET	GO:0010962	regulation of glucan biosynthetic process	8.83e-05
MET	GO:0043467	regulation of generation of precursor metabolites and energy	1.23e-04
MET	GO:0070873	regulation of glycogen metabolic process	1.40e-04
MET	GO:0032885	regulation of polysaccharide biosynthetic process	1.41e-04
MET	GO:0045936	negative regulation of phosphate metabolic process	1.52e-04
MET	GO:0010563	negative regulation of phosphorus metabolic process	1.52e-04
MET	GO:0005978	glycogen biosynthetic process	1.72e-04
MET	GO:0009250	glucan biosynthetic process	1.72e-04
MET	GO:0032881	regulation of polysaccharide metabolic process	1.72e-04
MET	GO:0016051	carbohydrate biosynthetic process	4.12e-04
MET	GO:0000271	polysaccharide biosynthetic process	4.65e-04
MET	GO:0005977	glycogen metabolic process	6.80e-04
MET	GO:0044042	glucan metabolic process	7.00e-04
MET	GO:0031016	pancreas development	7.00e-04
MET	GO:1900543	negative regulation of purine nucleotide metabolic process	7.39e-04
MET	GO:0045980	negative regulation of nucleotide metabolic process	8.69e-04
MET	GO:0006112	energy reserve metabolic process	8.90e-04
MET	GO:0043491	phosphatidylinositol 3-kinase/protein kinase B signal transduction	9.74e-04
MET	GO:0005976	polysaccharide metabolic process	1.25e-03
MET	GO:0043255	regulation of carbohydrate biosynthetic process	1.32e-03
MET	GO:0007173	epidermal growth factor receptor signaling pathway	1.35e-03
MET	GO:0045725	positive regulation of glycogen biosynthetic process	1.35e-03
MET	GO:0015980	energy derivation by oxidation of organic compounds	1.44e-03
MET	GO:0062012	regulation of small molecule metabolic process	1.44e-03
MET	GO:0070875	positive regulation of glycogen metabolic process	1.59e-03
MET	GO:0038127	ERBB signaling pathway	1.79e-03
MET	GO:0001952	regulation of cell-matrix adhesion	1.79e-03
MET	GO:0071902	positive regulation of protein serine/threonine kinase activity	2.45e-03
MET	GO:1903578	regulation of ATP metabolic process	2.89e-03
MET	GO:0030010	establishment of cell polarity	3.21e-03
MET	GO:0070507	regulation of microtubule cytoskeleton organization	3.41e-03
MET	GO:1902410	mitotic cytokinetic process	3.41e-03
MET	GO:0051897	positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3.91e-03
MET	GO:0043410	positive regulation of MAPK cascade	4.19e-03
MET	GO:2000058	regulation of ubiquitin-dependent protein catabolic process	4.21e-03
MET	GO:0001667	ameboidal-type cell migration	4.74e-03
MET	GO:0006109	regulation of carbohydrate metabolic process	4.74e-03
MET	GO:0035305	negative regulation of dephosphorylation	5.05e-03
MET	GO:0031334	positive regulation of protein-containing complex assembly	5.26e-03

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Related Drugs to MET_TFG

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 MET-TFG 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 MET_TFG

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
Tgene	TFG	C3714897	SPASTIC PARAPLEGIA 57, AUTOSOMAL RECESSIVE	5	CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Tgene	TFG	C1858338	Neuropathy, hereditary motor and sensory, Okinawa type	4	CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Tgene	TFG	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