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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:AFAP1_NTRK2

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: AFAP1_NTRK2
	KinaseFusionDB ID: KFG213
	FusionGDB2.0 ID: KFG213
		Hgene	Tgene
	Gene symbol	AFAP1	NTRK2
	Gene ID	60312	4915
	Gene name	actin filament associated protein 1	neurotrophic receptor tyrosine kinase 2
	Synonyms	AFAP\|AFAP-110\|AFAP110	DEE58\|EIEE58\|GP145-TrkB\|OBHD\|TRKB\|trk-B
	Cytomap	4p16.1	9q21.33
	Type of gene	protein-coding	protein-coding
	Description	actin filament-associated protein 1110 kDa actin filament-associated proteinactin filament-associated protein, 110 kDa	BDNF/NT-3 growth factors receptorBDNF-tropomyosine receptor kinase Bneurotrophic tyrosine kinase receptor type 2tropomyosin-related kinase Btyrosine kinase receptor B
	Modification date	20240305	20240411
	UniProtAcc	Q8N4X5	Q16620
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000513842, ENST00000358461, ENST00000360265, ENST00000382543, ENST00000420658,	ENST00000277120, ENST00000304053, ENST00000323115, ENST00000359847, ENST00000376208, ENST00000376213, ENST00000376214, ENST00000395866, ENST00000395882,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: AFAP1 [Title/Abstract] AND NTRK2 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	NTRK2(87342874)-AFAP1(7776630), # samples:2 AFAP1(7780489)-NTRK2(87356807), # 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

Kinase Fusion gene breakpoints across AFAP1 (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 NTRK2 (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-HT-7680-01A	AFAP1	chr4	7780489	NTRK2	chr9	87356807
ChimerDB4	TCGA-HT-7680	AFAP1	chr4	7780488	NTRK2	chr9	87356806

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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)
ENST00000360265	ENST00000376214	AFAP1	chr4	7780489	NTRK2	chr9	87356807	5391	1016
ENST00000360265	ENST00000376214	AFAP1	chr4	7780488	NTRK2	chr9	87356806	5391	1016

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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

>ENST00000360265_ENST00000376214_AFAP1_chr4_7780489_NTRK2_chr9_87356807_length(amino acids)=1016
MQITGSNNTLPLLLSAMEELIVELRLFLELLDHEYLTSTVREKKAVITNILLRIQSSKGFDVKDHAQKQETANSLPAPPQMPLPEIPQPW
LPPDSGPPPLPTSSLPEGYYEEAVPLSPGKAPEYITSNYDSDAMSSSYESYDEEEEDGKGKKTRHQWPSEEASMDLVKDAKICAFLLRKK
RFGQWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCNITYIPKDSKKKKHELKITQQGTDPLVLAVQSKEQAEQWLKVIKEAYSGCSGP
VDSECPPPPSSPVHKAELEKKLSSERPSSDGEGVVENGITTCNGKEQVKRKKSSKSEAKGTVSKVTGKKITKIISLGKKKPSTDEQTSSA
EEDVPTCGYLNVLSNSRWRERWCRVKDNKLIFHKDRTDLKTHIVSIPLRGCEVIPGLDSKHPLTFRLLRNGQEVAVLEASSSEDMGRWIG
ILLAETGSSTDPEALHYDYIDVEMSASVIQTAKQTFCFMNRRVISANPYLGGTSNGYAHPSGTALHYDDVPCINGSLKGKKPPVASNGVT
GKGKTLSSQPKKADPAAVVKRTGSSANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLF
LLKLARHSKFGMKDFSWFGFGKVKSRQGVGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKP
DTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMV
FEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDY
YRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHM

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

>ENST00000360265_ENST00000376214_AFAP1_chr4_7780488_NTRK2_chr9_87356806_length(amino acids)=1016
MQITGSNNTLPLLLSAMEELIVELRLFLELLDHEYLTSTVREKKAVITNILLRIQSSKGFDVKDHAQKQETANSLPAPPQMPLPEIPQPW
LPPDSGPPPLPTSSLPEGYYEEAVPLSPGKAPEYITSNYDSDAMSSSYESYDEEEEDGKGKKTRHQWPSEEASMDLVKDAKICAFLLRKK
RFGQWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCNITYIPKDSKKKKHELKITQQGTDPLVLAVQSKEQAEQWLKVIKEAYSGCSGP
VDSECPPPPSSPVHKAELEKKLSSERPSSDGEGVVENGITTCNGKEQVKRKKSSKSEAKGTVSKVTGKKITKIISLGKKKPSTDEQTSSA
EEDVPTCGYLNVLSNSRWRERWCRVKDNKLIFHKDRTDLKTHIVSIPLRGCEVIPGLDSKHPLTFRLLRNGQEVAVLEASSSEDMGRWIG
ILLAETGSSTDPEALHYDYIDVEMSASVIQTAKQTFCFMNRRVISANPYLGGTSNGYAHPSGTALHYDDVPCINGSLKGKKPPVASNGVT
GKGKTLSSQPKKADPAAVVKRTGSSANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLF
LLKLARHSKFGMKDFSWFGFGKVKSRQGVGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKP
DTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMV
FEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDY
YRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHM

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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/chr4:87342874/chr9:7776630)
- 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
AFAP1 Q8N4X5	NTRK2 Q16620
FUNCTION: May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation. {ECO:0000269\|PubMed:17412687}.	FUNCTION: Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (PubMed:7574684, PubMed:15494731). Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. {ECO:0000250\|UniProtKB:P15209, ECO:0000269\|PubMed:15494731, ECO:0000269\|PubMed:7574684}.

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).

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

- 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
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	7	12	295_365	230	322	Domain	Note=Ig-like C2-type 2
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	7	12	295_365	230	322	Domain	Note=Ig-like C2-type 2
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	10	20	538_807	386	823	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	10	21	538_807	386	839	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	7	12	538_807	230	322	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	7	12	538_807	386	478	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	7	17	538_807	386	823	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	8	13	538_807	386	478	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	8	14	538_807	386	538	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	8	15	538_807	386	554	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780488	NTRK2	87356806	ENST00000360265	8	19	538_807	386	839	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	10	20	538_807	386	823	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	10	21	538_807	386	839	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	7	12	538_807	230	322	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	7	12	538_807	386	478	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	7	17	538_807	386	823	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	8	13	538_807	386	478	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	8	14	538_807	386	538	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	8	15	538_807	386	554	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	AFAP1	7780489	NTRK2	87356807	ENST00000360265	8	19	538_807	386	839	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159

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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 >>>7_AFAP1_NTRK2	ENST00000360265	ENST00000376214	AFAP1	chr4	7780488	NTRK2	chr9	87356806	MQITGSNNTLPLLLSAMEELIVELRLFLELLDHEYLTSTVREKKAVITNILLRIQSSKGFDVKDHAQKQETANSLPAPPQMPLPEIPQPW LPPDSGPPPLPTSSLPEGYYEEAVPLSPGKAPEYITSNYDSDAMSSSYESYDEEEEDGKGKKTRHQWPSEEASMDLVKDAKICAFLLRKK RFGQWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCNITYIPKDSKKKKHELKITQQGTDPLVLAVQSKEQAEQWLKVIKEAYSGCSGP VDSECPPPPSSPVHKAELEKKLSSERPSSDGEGVVENGITTCNGKEQVKRKKSSKSEAKGTVSKVTGKKITKIISLGKKKPSTDEQTSSA EEDVPTCGYLNVLSNSRWRERWCRVKDNKLIFHKDRTDLKTHIVSIPLRGCEVIPGLDSKHPLTFRLLRNGQEVAVLEASSSEDMGRWIG ILLAETGSSTDPEALHYDYIDVEMSASVIQTAKQTFCFMNRRVISANPYLGGTSNGYAHPSGTALHYDDVPCINGSLKGKKPPVASNGVT GKGKTLSSQPKKADPAAVVKRTGSSANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLF LLKLARHSKFGMKDFSWFGFGKVKSRQGVGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKP DTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMV FEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDY YRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHM	1016
3D view using mol* of 7_AFAP1_NTRK2

PDB file >>>TKFP_14_AFAP1_NTRK2	ENST00000360265	ENST00000376214	AFAP1	chr4	7780489	NTRK2	chr9	87356807	MQITGSNNTLPLLLSAMEELIVELRLFLELLDHEYLTSTVREKKAVITNILLRIQSSKGFDVKDHAQKQETANSLPAPPQMPLPEIPQPW LPPDSGPPPLPTSSLPEGYYEEAVPLSPGKAPEYITSNYDSDAMSSSYESYDEEEEDGKGKKTRHQWPSEEASMDLVKDAKICAFLLRKK RFGQWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCNITYIPKDSKKKKHELKITQQGTDPLVLAVQSKEQAEQWLKVIKEAYSGCSGP VDSECPPPPSSPVHKAELEKKLSSERPSSDGEGVVENGITTCNGKEQVKRKKSSKSEAKGTVSKVTGKKITKIISLGKKKPSTDEQTSSA EEDVPTCGYLNVLSNSRWRERWCRVKDNKLIFHKDRTDLKTHIVSIPLRGCEVIPGLDSKHPLTFRLLRNGQEVAVLEASSSEDMGRWIG ILLAETGSSTDPEALHYDYIDVEMSASVIQTAKQTFCFMNRRVISANPYLGGTSNGYAHPSGTALHYDDVPCINGSLKGKKPPVASNGVT GKGKTLSSQPKKADPAAVVKRTGSSANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLF LLKLARHSKFGMKDFSWFGFGKVKSRQGVGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKP DTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMV FEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDY YRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHM	1016_AFAP1_NTRK2
PDB file >>>TKFP_15_AFAP1_NTRK2	ENST00000360265	ENST00000376214	AFAP1	chr4	7780488	NTRK2	chr9	87356806	MQITGSNNTLPLLLSAMEELIVELRLFLELLDHEYLTSTVREKKAVITNILLRIQSSKGFDVKDHAQKQETANSLPAPPQMPLPEIPQPW LPPDSGPPPLPTSSLPEGYYEEAVPLSPGKAPEYITSNYDSDAMSSSYESYDEEEEDGKGKKTRHQWPSEEASMDLVKDAKICAFLLRKK RFGQWTKLLCVIKDTKLLCYKSSKDQQPQMELPLQGCNITYIPKDSKKKKHELKITQQGTDPLVLAVQSKEQAEQWLKVIKEAYSGCSGP VDSECPPPPSSPVHKAELEKKLSSERPSSDGEGVVENGITTCNGKEQVKRKKSSKSEAKGTVSKVTGKKITKIISLGKKKPSTDEQTSSA EEDVPTCGYLNVLSNSRWRERWCRVKDNKLIFHKDRTDLKTHIVSIPLRGCEVIPGLDSKHPLTFRLLRNGQEVAVLEASSSEDMGRWIG ILLAETGSSTDPEALHYDYIDVEMSASVIQTAKQTFCFMNRRVISANPYLGGTSNGYAHPSGTALHYDDVPCINGSLKGKKPPVASNGVT GKGKTLSSQPKKADPAAVVKRTGSSANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLF LLKLARHSKFGMKDFSWFGFGKVKSRQGVGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKP DTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMV FEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDY YRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHM	1016_AFAP1_NTRK2

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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

AFAP1_NTRK2 does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/7_AFAP1_NTRK2.png

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.

7_AFAP1_NTRK2.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.

7_AFAP1_NTRK2_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
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Upadacitinib	-7.48223	-7.483230000000001	-19.9182
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Larotrectinib	-7.0564100000000005	-7.0564100000000005	-44.8198
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Binimetinib	-6.46828	-6.47698	-44.8788
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Binimetinib	-6.46828	-6.47698	-44.8788
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Tofacitinib	-6.45286	-6.46436	-35.1756
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Tofacitinib	-6.45286	-6.46436	-35.1756
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Pralsetinib	-6.05066	-6.14216	-35.5261
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Afatinib	-5.97342	-6.15572	-44.9156
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Afatinib	-5.97342	-6.15572	-44.9156
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Afatinib	-5.97202	-6.15572	-44.9156
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Pralsetinib	-5.83248	-5.92398	-31.1376
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Tofacitinib	-5.82808	-5.839580000000001	-14.4993
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Tofacitinib	-5.82808	-5.839580000000001	-14.4993
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Acalabrutinib	-5.70958	-5.72368	-29.5498
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Acalabrutinib	-5.70958	-5.72368	-29.5498
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Larotrectinib	-5.50849	-5.50849	-30.9749
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Osimertinib	-5.450019999999999	-5.45772	-39.0181
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Larotrectinib	-5.37021	-5.37021	-37.9296
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Upadacitinib	-5.3673	-5.3683	-15.5968
7_AFAP1_NTRK2-DOCK_HTVS_1-001	Pexidartinib	-5.35471	-6.05551	-42.621

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Kinase-Substrate Information of AFAP1_NTRK2

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
NTRK2	Q16620	human	NTRK2	Q16620	Y516	PVIENPQyFGITNSQ
NTRK2	Q16620	human	SHC3	Q92529-2	Y218	GDGSDHPyyNSIPSK
NTRK2	Q16620	human	SHC3	Q92529-2	Y256	FAGKEQTyyQGRHLG
NTRK2	Q16620	human	KCNA3	P22001	Y499	EGEEQSQyMHVGsCQ
NTRK2	Q16620	human	KCNA3	P22001	Y161	PSFDAILyyyQSGGR	BTB_2
NTRK2	Q16620	human	KCNA3	P22001	Y162	SFDAILyyyQSGGRI	BTB_2
NTRK2	Q16620	human	SHC3	Q92529-2	Y301	PTGEAPTyVNTQQIP
NTRK2	Q16620	human	SHC3	Q92529-2	Y257	AGKEQTyyQGRHLGD
NTRK2	Q16620	human	SHC3	Q92529-2	Y283	RQGSSDIySTPEGKL
NTRK2	Q16620	human	SHC3	Q92529-2	Y219	DGSDHPyyNSIPSKM
NTRK2	Q16620	human	KCNA3	P22001	Y163	FDAILyyyQSGGRIR	BTB_2

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
NTRK2	ID	Description	0.00e+00
NTRK2	GO:0021537	telencephalon development	3.61e-02
NTRK2	GO:0030900	forebrain development	3.61e-02
NTRK2	GO:0099550	trans-synaptic signalin	1.59e-03
NTRK2	GO:0048935	peripheral nervous system neuron development	3.61e-02
NTRK2	GO:0060221	retinal rod cell differentiation	3.61e-02
NTRK2	GO:2000811	negative regulation of anoikis	3.61e-02
NTRK2	GO:0021554	optic nerve development	3.61e-02
NTRK2	GO:2000209	regulation of anoikis	3.61e-02
NTRK2	GO:0022038	corpus callosum development	3.61e-02
NTRK2	GO:0014047	glutamate secretion	3.61e-02
NTRK2	GO:0022011	myelination in peripheral nervous system	3.61e-02
NTRK2	GO:0032292	peripheral nervous system axon ensheathment	3.61e-02
NTRK2	GO:1902430	negative regulation of amyloid-beta formation	3.61e-02
NTRK2	GO:0060219	camera-type eye photoreceptor cell differentiation	3.61e-02
NTRK2	GO:0014044	Schwann cell development	3.61e-02
NTRK2	GO:1902992	negative regulation of amyloid precursor protein catabolic process	3.61e-02
NTRK2	GO:0042462	eye photoreceptor cell development	3.61e-02
NTRK2	GO:0043276	anoikis	3.61e-02
NTRK2	GO:0014037	Schwann cell differentiation	3.74e-02
NTRK2	GO:0038179	neurotrophin signaling pathway	3.74e-02
NTRK2	GO:1990090	cellular response to nerve growth factor stimulus	3.75e-02
NTRK2	GO:0001754	eye photoreceptor cell differentiation	3.75e-02
NTRK2	GO:1902003	regulation of amyloid-beta formation	3.75e-02
NTRK2	GO:1990089	response to nerve growth factor	3.75e-02
NTRK2	GO:0042461	photoreceptor cell development	3.75e-02
NTRK2	GO:1902991	regulation of amyloid precursor protein catabolic process	3.75e-02
NTRK2	GO:0034205	amyloid-beta formation	3.75e-02
NTRK2	GO:0021545	cranial nerve development	3.75e-02
NTRK2	GO:0051965	positive regulation of synapse assembly	3.75e-02
NTRK2	GO:0046530	photoreceptor cell differentiation	3.75e-02
NTRK2	GO:0050435	amyloid-beta metabolic process	3.75e-02
NTRK2	GO:0060042	retina morphogenesis in camera-type eye	3.75e-02
NTRK2	GO:0015800	acidic amino acid transport	3.75e-02
NTRK2	GO:0042490	mechanoreceptor differentiation	3.75e-02
NTRK2	GO:0042987	amyloid precursor protein catabolic process	3.75e-02
NTRK2	GO:0019226	transmission of nerve impulse	3.75e-02
NTRK2	GO:0050772	positive regulation of axonogenesis	4.05e-02
NTRK2	GO:0003407	neural retina development	4.05e-02
NTRK2	GO:0007422	peripheral nervous system development	4.05e-02
NTRK2	GO:0001570	vasculogenesis	4.05e-02
NTRK2	GO:0071230	cellular response to amino acid stimulus	4.05e-02
NTRK2	GO:0021954	central nervous system neuron development	4.05e-02
NTRK2	GO:0071229	cellular response to acid chemical	4.05e-02
NTRK2	GO:0042982	amyloid precursor protein metabolic process	4.05e-02
NTRK2	GO:0021675	nerve development	4.05e-02
NTRK2	GO:0006835	dicarboxylic acid transport	4.05e-02
NTRK2	GO:0033138	positive regulation of peptidyl-serine phosphorylation	4.05e-02
NTRK2	GO:0007631	feeding behavior	4.05e-02
NTRK2	GO:0048709	oligodendrocyte differentiation	4.05e-02

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Related Drugs to AFAP1_NTRK2

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 AFAP1-NTRK2 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 AFAP1_NTRK2

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	NTRK2	C0011570	Mental Depression	5	PSYGENET
Tgene	NTRK2	C0011581	Depressive disorder	5	PSYGENET
Tgene	NTRK2	C0041696	Unipolar Depression	5	PSYGENET
Tgene	NTRK2	C0525045	Mood Disorders	5	PSYGENET
Tgene	NTRK2	C1269683	Major Depressive Disorder	5	PSYGENET
Tgene	NTRK2	C3151303	Obesity, Hyperphagia, and Developmental Delay	4	CTD_human;GENOMICS_ENGLAND;UNIPROT
Tgene	NTRK2	C0005586	Bipolar Disorder	3	CTD_human;PSYGENET
Tgene	NTRK2	C4693367	EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 58	3	GENOMICS_ENGLAND;UNIPROT
Tgene	NTRK2	C0009171	Cocaine Abuse	2	CTD_human
Tgene	NTRK2	C0036341	Schizophrenia	2	PSYGENET
Tgene	NTRK2	C0038220	Status Epilepticus	2	CTD_human
Tgene	NTRK2	C0236736	Cocaine-Related Disorders	2	CTD_human
Tgene	NTRK2	C0270823	Petit mal status	2	CTD_human
Tgene	NTRK2	C0311335	Grand Mal Status Epilepticus	2	CTD_human
Tgene	NTRK2	C0393734	Complex Partial Status Epilepticus	2	CTD_human
Tgene	NTRK2	C0600427	Cocaine Dependence	2	CTD_human
Tgene	NTRK2	C0751217	Hyperkinesia, Generalized	2	CTD_human
Tgene	NTRK2	C0751522	Status Epilepticus, Subclinical	2	CTD_human
Tgene	NTRK2	C0751523	Non-Convulsive Status Epilepticus	2	CTD_human
Tgene	NTRK2	C0751524	Simple Partial Status Epilepticus	2	CTD_human
Tgene	NTRK2	C3887506	Hyperkinesia	2	CTD_human

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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