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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:AKAP9_BRAF

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: AKAP9_BRAF
	KinaseFusionDB ID: KFG255
	FusionGDB2.0 ID: KFG255
		Hgene	Tgene
	Gene symbol	AKAP9	BRAF
	Gene ID	10142	673
	Gene name	A-kinase anchoring protein 9	B-Raf proto-oncogene, serine/threonine kinase
	Synonyms	AKAP-9\|AKAP350\|AKAP450\|CG-NAP\|HYPERION\|LQT11\|MU-RMS-40.16A\|PPP1R45\|PRKA9\|YOTIAO	B-RAF1\|B-raf\|BRAF-1\|BRAF1\|NS7\|RAFB1
	Cytomap	7q21.2	7q34
	Type of gene	protein-coding	protein-coding
	Description	A-kinase anchor protein 9A kinase (PRKA) anchor protein (yotiao) 9A kinase (PRKA) anchor protein 9A-kinase anchor protein 350 kDaA-kinase anchor protein 450 kDaAKAP 120-like proteinAKAP9-BRAF fusion proteincentrosome- and Golgi-localized PKN-associ	serine/threonine-protein kinase B-raf94 kDa B-raf proteinB-Raf proto-oncogene serine/threonine-protein kinase (p94)B-Raf serine/threonine-proteinmurine sarcoma viral (v-raf) oncogene homolog B1proto-oncogene B-Rafv-raf murine sarcoma viral oncogene
	Modification date	20240407	20240416
	UniProtAcc	Q99996	P15056
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000356239, ENST00000358100, ENST00000359028, ENST00000394564, ENST00000491695,	ENST00000288602,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: AKAP9 [Title/Abstract] AND BRAF [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	AKAP9(91632550)-BRAF(140434354), # samples:1 AKAP9(91632550)-BRAF(140487386), # samples:1 AKAP9(91739875)-BRAF(140513187), # samples:1

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	AKAP9	GO:0031503	protein-containing complex localization	19218243
Hgene	AKAP9	GO:1903358	regulation of Golgi organization	27666745
Tgene	BRAF	GO:0000165	MAPK cascade	18567582\|29433126
Tgene	BRAF	GO:0006468	protein phosphorylation	17563371
Tgene	BRAF	GO:0007173	epidermal growth factor receptor signaling pathway	18567582
Tgene	BRAF	GO:0010828	positive regulation of glucose transmembrane transport	23010278
Tgene	BRAF	GO:0033138	positive regulation of peptidyl-serine phosphorylation	19667065
Tgene	BRAF	GO:0043066	negative regulation of apoptotic process	19667065
Tgene	BRAF	GO:0070374	positive regulation of ERK1 and ERK2 cascade	22065586
Tgene	BRAF	GO:0071277	cellular response to calcium ion	18567582
Tgene	BRAF	GO:0090150	establishment of protein localization to membrane	23010278

Kinase Fusion gene breakpoints across AKAP9 (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 BRAF (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
ChiTaRS5.0	FN170090	AKAP9	chr7	91739875	BRAF	chr7	140513187
ChimerDB4	AY803272	AKAP9	chr7	91632550	BRAF	chr7	140434354
ChimerKB3	.	AKAP9	chr7	91632549	BRAF	chr7	140487384
ChiTaRS5.0	AY803272	AKAP9	chr7	91632550	BRAF	chr7	140487386
ChimerKB3	.	AKAP9	chr7	91470486	BRAF	chr7	140080822
COSMIC	900219	AKAP9	chr7	91632913	BRAF	chr7	140489178

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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)
ENST00000356239	ENST00000288602	AKAP9	chr7	91632550	BRAF	chr7	140487386	4830	1502
ENST00000356239	ENST00000288602	AKAP9	chr7	91632549	BRAF	chr7	140487384	4830	1502

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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

>ENST00000356239_ENST00000288602_AKAP9_chr7_91632550_BRAF_chr7_140487386_length(amino acids)=1502
MFSPAFLAEAMEDEERQKKLEAGKAKLAQFRQRKAQSDGQSPSKKQKKKRKTSSSKHDVSAHHDLNIDQSQCNEMYINSSQRVESTVIPE
STIMRTLHSGEITSHEQGFSVELESEISTTADDCSSEVNGCSFVMRTGKPTNLLREEEFGVDDSYSEQGAQDSPTHLEMMESELAGKQHE
IEELNRELEEMRVTYGTEGLQQLQEFEAAIKQRDGIITQLTANLQQARREKDETMREFLELTEQSQKLQIQFQQLQASETLRNSTHSSTA
ADLLQAKQQILTHQQQLEEQDHLLEDYQKKKEDFTMQISFLQEKIKVYEMEQDKKVENSNKEEIQEKETIIEELNTKIIEEEKKTLELKD
KLTTADKLLGELQEQIVQKNQEIKNMKLELTNSKQKERQSSEEIKQLMGTVEELQKRNHKDSQFETDIVQRMEQETQRKLEQLRAELDEM
YGQQIVQMKQELIRQHMAQMEEMKTRHKGEMENALRSYSNITVNEDQIKLMNVAINELNIKLQDTNSQKEKLKEELGLILEEKCALQRQL
EDLVEELSFSREQIQRARQTIAEQESKLNEAHKSLSTVEDLKAEIVSASESRKELELKHEAEVTNYKIKLEMLEKEKNAVLDRMAESQEA
ELERLRTQLLFSHEEELSKLKEDLEIEHRINIEKLKDNLGIHYKQQIDGLQNEMSQKIETMQFEKDNLITKQNQLILEISKLKDLQQSLV
NSKSEEMTLQINELQKEIEILRQEEKEKGTLEQEVQELQLKTELLEKQMKEKENDLQEKFAQLEAENSILKDEKKTLEDMLKIHTPVSQE
ERLIFLDSIKSKSKDSVWEKEIEILIEENEDLKQQCIQLNEEIEKQRNTFSFAEKNFEVNYQELQEEYACLLKVKDDLEDSKNKQELEYK
SKLKALNEELHLQRINPTTVKMKSSVFDEDKTFVAETLEMGEVVEKDTTELMEKLEVTKREKLELSQRLSDLSEQLKQKHGEISFLNEEV
KSLKQEKEQVSLRCRELEIIINHNRAENVQSCDTQVSSLLDGVVTMTSRGAEGSVSKVNKSFGEESKIMVEDKVSFENMTVGEESKQEQL
ILDHLPSVTKESSLRATQPSENDKLQKELNVLKSEQDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSSSED
RNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQ
LAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLS
GSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDER

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

>ENST00000356239_ENST00000288602_AKAP9_chr7_91632549_BRAF_chr7_140487384_length(amino acids)=1502
MFSPAFLAEAMEDEERQKKLEAGKAKLAQFRQRKAQSDGQSPSKKQKKKRKTSSSKHDVSAHHDLNIDQSQCNEMYINSSQRVESTVIPE
STIMRTLHSGEITSHEQGFSVELESEISTTADDCSSEVNGCSFVMRTGKPTNLLREEEFGVDDSYSEQGAQDSPTHLEMMESELAGKQHE
IEELNRELEEMRVTYGTEGLQQLQEFEAAIKQRDGIITQLTANLQQARREKDETMREFLELTEQSQKLQIQFQQLQASETLRNSTHSSTA
ADLLQAKQQILTHQQQLEEQDHLLEDYQKKKEDFTMQISFLQEKIKVYEMEQDKKVENSNKEEIQEKETIIEELNTKIIEEEKKTLELKD
KLTTADKLLGELQEQIVQKNQEIKNMKLELTNSKQKERQSSEEIKQLMGTVEELQKRNHKDSQFETDIVQRMEQETQRKLEQLRAELDEM
YGQQIVQMKQELIRQHMAQMEEMKTRHKGEMENALRSYSNITVNEDQIKLMNVAINELNIKLQDTNSQKEKLKEELGLILEEKCALQRQL
EDLVEELSFSREQIQRARQTIAEQESKLNEAHKSLSTVEDLKAEIVSASESRKELELKHEAEVTNYKIKLEMLEKEKNAVLDRMAESQEA
ELERLRTQLLFSHEEELSKLKEDLEIEHRINIEKLKDNLGIHYKQQIDGLQNEMSQKIETMQFEKDNLITKQNQLILEISKLKDLQQSLV
NSKSEEMTLQINELQKEIEILRQEEKEKGTLEQEVQELQLKTELLEKQMKEKENDLQEKFAQLEAENSILKDEKKTLEDMLKIHTPVSQE
ERLIFLDSIKSKSKDSVWEKEIEILIEENEDLKQQCIQLNEEIEKQRNTFSFAEKNFEVNYQELQEEYACLLKVKDDLEDSKNKQELEYK
SKLKALNEELHLQRINPTTVKMKSSVFDEDKTFVAETLEMGEVVEKDTTELMEKLEVTKREKLELSQRLSDLSEQLKQKHGEISFLNEEV
KSLKQEKEQVSLRCRELEIIINHNRAENVQSCDTQVSSLLDGVVTMTSRGAEGSVSKVNKSFGEESKIMVEDKVSFENMTVGEESKQEQL
ILDHLPSVTKESSLRATQPSENDKLQKELNVLKSEQDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSSSED
RNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQ
LAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLS
GSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDER

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

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/chr7:91632550/chr7:140434354)
- 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
AKAP9 Q99996	BRAF P15056
FUNCTION: Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus. Required to maintain the integrity of the Golgi apparatus (PubMed:10202149, PubMed:15047863). Required for microtubule nucleation at the cis-side of the Golgi apparatus (PubMed:15047863, PubMed:19242490). Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase (PubMed:25657325). In complex with PDE4DIP isoform 13/MMG8/SMYLE, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745, PubMed:28814570). In complex with PDE4DIP isoform 13/MMG8/SMYLE, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension also from the centrosome to the cell periphery (PubMed:29162697). {ECO:0000269\|PubMed:10202149, ECO:0000269\|PubMed:15047863, ECO:0000269\|PubMed:19242490, ECO:0000269\|PubMed:25657325, ECO:0000269\|PubMed:27666745, ECO:0000269\|PubMed:28814570, ECO:0000269\|PubMed:29162697}.; FUNCTION: [Isoform 4]: Associated with the N-methyl-D-aspartate receptor and is specifically found in the neuromuscular junction (NMJ) as well as in neuronal synapses, suggesting a role in the organization of postsynaptic specializations. {ECO:0000269\|PubMed:9482789}.	FUNCTION: Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269\|PubMed:1508179, ECO:0000269\|PubMed:21441910, ECO:0000269\|PubMed:29433126, ECO:0000269\|PubMed:36402789, ECO:0000305}.

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

AKAP9

91632549

BRAF

140487384

ENST00000356239

457_717

380

767

Domain

Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159

Tgene

AKAP9

91632550

BRAF

140487386

ENST00000356239

457_717

380

767

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 >>>19_AKAP9_BRAF	ENST00000356239	ENST00000288602	AKAP9	chr7	91632549	BRAF	chr7	140487384	MFSPAFLAEAMEDEERQKKLEAGKAKLAQFRQRKAQSDGQSPSKKQKKKRKTSSSKHDVSAHHDLNIDQSQCNEMYINSSQRVESTVIPE STIMRTLHSGEITSHEQGFSVELESEISTTADDCSSEVNGCSFVMRTGKPTNLLREEEFGVDDSYSEQGAQDSPTHLEMMESELAGKQHE IEELNRELEEMRVTYGTEGLQQLQEFEAAIKQRDGIITQLTANLQQARREKDETMREFLELTEQSQKLQIQFQQLQASETLRNSTHSSTA ADLLQAKQQILTHQQQLEEQDHLLEDYQKKKEDFTMQISFLQEKIKVYEMEQDKKVENSNKEEIQEKETIIEELNTKIIEEEKKTLELKD KLTTADKLLGELQEQIVQKNQEIKNMKLELTNSKQKERQSSEEIKQLMGTVEELQKRNHKDSQFETDIVQRMEQETQRKLEQLRAELDEM YGQQIVQMKQELIRQHMAQMEEMKTRHKGEMENALRSYSNITVNEDQIKLMNVAINELNIKLQDTNSQKEKLKEELGLILEEKCALQRQL EDLVEELSFSREQIQRARQTIAEQESKLNEAHKSLSTVEDLKAEIVSASESRKELELKHEAEVTNYKIKLEMLEKEKNAVLDRMAESQEA ELERLRTQLLFSHEEELSKLKEDLEIEHRINIEKLKDNLGIHYKQQIDGLQNEMSQKIETMQFEKDNLITKQNQLILEISKLKDLQQSLV NSKSEEMTLQINELQKEIEILRQEEKEKGTLEQEVQELQLKTELLEKQMKEKENDLQEKFAQLEAENSILKDEKKTLEDMLKIHTPVSQE ERLIFLDSIKSKSKDSVWEKEIEILIEENEDLKQQCIQLNEEIEKQRNTFSFAEKNFEVNYQELQEEYACLLKVKDDLEDSKNKQELEYK SKLKALNEELHLQRINPTTVKMKSSVFDEDKTFVAETLEMGEVVEKDTTELMEKLEVTKREKLELSQRLSDLSEQLKQKHGEISFLNEEV KSLKQEKEQVSLRCRELEIIINHNRAENVQSCDTQVSSLLDGVVTMTSRGAEGSVSKVNKSFGEESKIMVEDKVSFENMTVGEESKQEQL ILDHLPSVTKESSLRATQPSENDKLQKELNVLKSEQDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSSSED RNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQ LAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLS GSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDER	1502
3D view using mol* of 19_AKAP9_BRAF

PDB file >>>TKFP_32_AKAP9_BRAF	ENST00000356239	ENST00000288602	AKAP9	chr7	91632550	BRAF	chr7	140487386	MFSPAFLAEAMEDEERQKKLEAGKAKLAQFRQRKAQSDGQSPSKKQKKKRKTSSSKHDVSAHHDLNIDQSQCNEMYINSSQRVESTVIPE STIMRTLHSGEITSHEQGFSVELESEISTTADDCSSEVNGCSFVMRTGKPTNLLREEEFGVDDSYSEQGAQDSPTHLEMMESELAGKQHE IEELNRELEEMRVTYGTEGLQQLQEFEAAIKQRDGIITQLTANLQQARREKDETMREFLELTEQSQKLQIQFQQLQASETLRNSTHSSTA ADLLQAKQQILTHQQQLEEQDHLLEDYQKKKEDFTMQISFLQEKIKVYEMEQDKKVENSNKEEIQEKETIIEELNTKIIEEEKKTLELKD KLTTADKLLGELQEQIVQKNQEIKNMKLELTNSKQKERQSSEEIKQLMGTVEELQKRNHKDSQFETDIVQRMEQETQRKLEQLRAELDEM YGQQIVQMKQELIRQHMAQMEEMKTRHKGEMENALRSYSNITVNEDQIKLMNVAINELNIKLQDTNSQKEKLKEELGLILEEKCALQRQL EDLVEELSFSREQIQRARQTIAEQESKLNEAHKSLSTVEDLKAEIVSASESRKELELKHEAEVTNYKIKLEMLEKEKNAVLDRMAESQEA ELERLRTQLLFSHEEELSKLKEDLEIEHRINIEKLKDNLGIHYKQQIDGLQNEMSQKIETMQFEKDNLITKQNQLILEISKLKDLQQSLV NSKSEEMTLQINELQKEIEILRQEEKEKGTLEQEVQELQLKTELLEKQMKEKENDLQEKFAQLEAENSILKDEKKTLEDMLKIHTPVSQE ERLIFLDSIKSKSKDSVWEKEIEILIEENEDLKQQCIQLNEEIEKQRNTFSFAEKNFEVNYQELQEEYACLLKVKDDLEDSKNKQELEYK SKLKALNEELHLQRINPTTVKMKSSVFDEDKTFVAETLEMGEVVEKDTTELMEKLEVTKREKLELSQRLSDLSEQLKQKHGEISFLNEEV KSLKQEKEQVSLRCRELEIIINHNRAENVQSCDTQVSSLLDGVVTMTSRGAEGSVSKVNKSFGEESKIMVEDKVSFENMTVGEESKQEQL ILDHLPSVTKESSLRATQPSENDKLQKELNVLKSEQDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSSSED RNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQ LAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLS GSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDER	1502_AKAP9_BRAF
PDB file >>>TKFP_33_AKAP9_BRAF	ENST00000356239	ENST00000288602	AKAP9	chr7	91632549	BRAF	chr7	140487384	MFSPAFLAEAMEDEERQKKLEAGKAKLAQFRQRKAQSDGQSPSKKQKKKRKTSSSKHDVSAHHDLNIDQSQCNEMYINSSQRVESTVIPE STIMRTLHSGEITSHEQGFSVELESEISTTADDCSSEVNGCSFVMRTGKPTNLLREEEFGVDDSYSEQGAQDSPTHLEMMESELAGKQHE IEELNRELEEMRVTYGTEGLQQLQEFEAAIKQRDGIITQLTANLQQARREKDETMREFLELTEQSQKLQIQFQQLQASETLRNSTHSSTA ADLLQAKQQILTHQQQLEEQDHLLEDYQKKKEDFTMQISFLQEKIKVYEMEQDKKVENSNKEEIQEKETIIEELNTKIIEEEKKTLELKD KLTTADKLLGELQEQIVQKNQEIKNMKLELTNSKQKERQSSEEIKQLMGTVEELQKRNHKDSQFETDIVQRMEQETQRKLEQLRAELDEM YGQQIVQMKQELIRQHMAQMEEMKTRHKGEMENALRSYSNITVNEDQIKLMNVAINELNIKLQDTNSQKEKLKEELGLILEEKCALQRQL EDLVEELSFSREQIQRARQTIAEQESKLNEAHKSLSTVEDLKAEIVSASESRKELELKHEAEVTNYKIKLEMLEKEKNAVLDRMAESQEA ELERLRTQLLFSHEEELSKLKEDLEIEHRINIEKLKDNLGIHYKQQIDGLQNEMSQKIETMQFEKDNLITKQNQLILEISKLKDLQQSLV NSKSEEMTLQINELQKEIEILRQEEKEKGTLEQEVQELQLKTELLEKQMKEKENDLQEKFAQLEAENSILKDEKKTLEDMLKIHTPVSQE ERLIFLDSIKSKSKDSVWEKEIEILIEENEDLKQQCIQLNEEIEKQRNTFSFAEKNFEVNYQELQEEYACLLKVKDDLEDSKNKQELEYK SKLKALNEELHLQRINPTTVKMKSSVFDEDKTFVAETLEMGEVVEKDTTELMEKLEVTKREKLELSQRLSDLSEQLKQKHGEISFLNEEV KSLKQEKEQVSLRCRELEIIINHNRAENVQSCDTQVSSLLDGVVTMTSRGAEGSVSKVNKSFGEESKIMVEDKVSFENMTVGEESKQEQL ILDHLPSVTKESSLRATQPSENDKLQKELNVLKSEQDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSSSED RNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQ LAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLS GSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDER	1502_AKAP9_BRAF

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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

AKAP9_BRAF does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/19_AKAP9_BRAF.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.

19_AKAP9_BRAF.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.

19_AKAP9_BRAF_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
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Neratinib	-8.1484	-8.3307	-47.0437
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Neratinib	-8.1484	-8.3307	-47.0437
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Acalabrutinib	-7.941789999999999	-7.955889999999999	-43.7382
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Acalabrutinib	-7.941789999999999	-7.955889999999999	-43.7382
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Pexidartinib	-7.915210000000001	-8.616010000000001	-41.0086
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Pexidartinib	-7.915210000000001	-8.616010000000001	-41.0086
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Midostaurin	-7.58125	-7.58125	-49.4291
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Neratinib	-7.467860000000001	-7.653760000000001	-44.7525
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Zanubrutinib	-7.46563	-7.46563	-41.9919
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Ibrutinib	-7.266660000000001	-7.266660000000001	-48.1168
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Acalabrutinib	-6.72611	-6.74021	-46.118
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Acalabrutinib	-6.72611	-6.74021	-46.118
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Midostaurin	-6.6803	-6.6803	-48.7289
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Midostaurin	-6.2609900000000005	-6.2609900000000005	-50.1829
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Netarsudil	-6.12105	-6.13215	-47.983999999999995
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Netarsudil	-6.12105	-6.13215	-47.983999999999995
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Axitinib	-6.0109699999999995	-6.01417	-41.2245
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Lapatinib	-5.9949699999999995	-6.0837699999999995	-52.9724
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Lapatinib	-5.94945	-6.03825	-52.824
19_AKAP9_BRAF_vsw_1-DOCK_HTVS_1-001	Pralsetinib	-5.8501199999999995	-5.9416199999999995	-46.9968

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Kinase-Substrate Information of AKAP9_BRAF

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
BRAF	P15056	human	SLC9A1	P19634	T653	LRsYNRHtLVADPyE	NEXCaM_BD
BRAF	P15056	human	EEF1A1	P68104	T88	EtSkyyVtIIDAPGH	GTP_EFTU
BRAF	P15056	human	BRAF	P15056	S465	tVGQRIGsGsFGtVY	PK_Tyr_Ser-Thr
BRAF	P15056	human	MAP2K1	Q02750	S222	LIDsMANsFVGtRSY	Pkinase
BRAF	P15056	human	EEF1A2	Q05639	S21	GHVDSGkstttGHLI	GTP_EFTU
BRAF	P15056	human	MAP2K1	Q02750	S218	VsGQLIDsMANsFVG	Pkinase
BRAF	P15056	human	TTK	P33981	S281	VPVNLLNsPDCDVkt
BRAF	P15056	human	BAD	Q92934	S99	PFrGrsRsAPPNLWA	Bcl-2_BAD
BRAF	P15056	human	MAP2K2	P36507	S222	VsGQLIDsMANsFVG	Pkinase
BRAF	P15056	human	BAD	Q92934	S75	EIRsRHssyPAGtED	Bcl-2_BAD
BRAF	P15056	human	NANOG	Q9H9S0	S68	LIQDsPDsStsPKGK
BRAF	P15056	human	EEF1A1	P68104	S21	GHVDSGkstttGHLI	GTP_EFTU
BRAF	P15056	human	BRAF	P15056	S614	SHQFEQLsGSILWMA	PK_Tyr_Ser-Thr
BRAF	P15056	human	BAD	Q92934	S118	GRELRRMsDEFVDsF	Bcl-2_BAD
BRAF	P15056	human	BRAF	P15056	S467	GQRIGsGsFGtVYkG	PK_Tyr_Ser-Thr
BRAF	P15056	human	BRAF	P15056	T373	APNVHINtIEPVNID
BRAF	P15056	human	MAP2K2	P36507	S226	LIDsMANsFVGtRSY	Pkinase
BRAF	P15056	human	TTK	P33981	S436	VFSVskQsPPIsTSk
BRAF	P15056	human	BAD	Q92934	S134	KGLPRPKsAGtAtQM	Bcl-2_BAD

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
BRAF	ID	Description	0.00e+00
BRAF	GO:0048679	regulation of axon regeneration	5.62e-05
BRAF	GO:0030878	thyroid gland development	5.62e-05
BRAF	GO:0035270	endocrine system development	5.62e-05
BRAF	GO:0070570	regulation of neuron projection regeneration	5.62e-05
BRAF	GO:0048538	thymus development	1.42e-04
BRAF	GO:0031103	axon regeneration	1.42e-04
BRAF	GO:0060324	face development	1.42e-04
BRAF	GO:0031102	neuron projection regeneration	1.74e-04
BRAF	GO:0050772	positive regulation of axonogenesis	3.79e-04
BRAF	GO:0048678	response to axon injury	4.26e-04
BRAF	GO:0060502	epithelial cell proliferation involved in lung morphogenesis	5.02e-04
BRAF	GO:0060439	trachea morphogenesis	5.09e-04
BRAF	GO:0048534	hematopoietic or lymphoid organ development	5.09e-04
BRAF	GO:0033674	positive regulation of kinase activity	5.09e-04
BRAF	GO:0048308	organelle inheritance	7.57e-04
BRAF	GO:0048313	Golgi inheritance	7.57e-04
BRAF	GO:0061684	chaperone-mediated autophagy	7.57e-04
BRAF	GO:1903358	regulation of Golgi organization	8.17e-04
BRAF	GO:0051347	positive regulation of transferase activity	8.44e-04
BRAF	GO:0060438	trachea development	9.59e-04
BRAF	GO:2000641	regulation of early endosome to late endosome transport	9.59e-04
BRAF	GO:0010720	positive regulation of cell development	9.59e-04
BRAF	GO:0050770	regulation of axonogenesis	1.21e-03
BRAF	GO:1903034	regulation of response to wounding	1.55e-03
BRAF	GO:0044342	type B pancreatic cell proliferation	1.85e-03
BRAF	GO:0031099	regeneration	1.92e-03
BRAF	GO:0002520	immune system development	2.09e-03
BRAF	GO:1903649	regulation of cytoplasmic transport	2.16e-03
BRAF	GO:0043550	regulation of lipid kinase activity	3.11e-03
BRAF	GO:0050769	positive regulation of neurogenesis	3.35e-03
BRAF	GO:0045022	early endosome to late endosome transport	3.60e-03
BRAF	GO:0060428	lung epithelium development	3.60e-03
BRAF	GO:0035987	endodermal cell differentiation	4.20e-03
BRAF	GO:0098927	vesicle-mediated transport between endosomal compartments	4.20e-03
BRAF	GO:0048009	insulin-like growth factor receptor signaling pathway	4.60e-03
BRAF	GO:0051962	positive regulation of nervous system development	4.69e-03
BRAF	GO:0060425	lung morphogenesis	4.69e-03
BRAF	GO:0018105	peptidyl-serine phosphorylation	4.74e-03
BRAF	GO:0001706	endoderm formation	5.11e-03
BRAF	GO:0018209	peptidyl-serine modification	5.11e-03
BRAF	GO:0046902	regulation of mitochondrial membrane permeability	5.41e-03
BRAF	GO:0070371	ERK1 and ERK2 cascade	6.22e-03
BRAF	GO:0048645	animal organ formation	6.22e-03
BRAF	GO:0035019	somatic stem cell population maintenance	6.45e-03
BRAF	GO:0006414	translational elongation	6.46e-03
BRAF	GO:0071260	cellular response to mechanical stimulus	6.46e-03
BRAF	GO:0010506	regulation of autophagy	6.46e-03
BRAF	GO:0031346	positive regulation of cell projection organization	6.46e-03
BRAF	GO:0090559	regulation of membrane permeability	6.84e-03

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Related Drugs to AKAP9_BRAF

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 AKAP9-BRAF 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
AKAP9-BRAF AND Trametinib		30792255	2019-03-01	10.1542/peds.2018-2469	Giant Congenital Melanocytic Nevus Treated With Trametinib.
AKAP9-BRAF AND Brigatinib	HIP1-ALK AND Brigatinib	34687488	2021-11	10.1002/gcc.23005	Clinicopathological features and resistance mechanisms in HIP1-ALK-rearranged lung cancer: A multicenter study.

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Related Diseases to AKAP9_BRAF

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene	Tgene	Disease	Source	PMID
AKAP9	BRAF	Thyroid Gland Papillary Carcinoma	MyCancerGenome
AKAP9	BRAF	Low-Grade Glioma	MyCancerGenome
AKAP9	BRAF	Nos	MyCancerGenome
AKAP9	BRAF	Pancreatic Adenocarcinoma	MyCancerGenome
AKAP9	BRAF	Pilocytic Astrocytoma	MyCancerGenome
AKAP9	BRAF	Astrocytoma	MyCancerGenome

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	AKAP9	C2678483	Long Qt Syndrome 11	4	CLINGEN;CTD_human;GENOMICS_ENGLAND;UNIPROT
Tgene	BRAF	C0025202	melanoma	24	CGI;CTD_human;UNIPROT
Tgene	BRAF	C1275081	Cardio-facio-cutaneous syndrome	14	CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Tgene	BRAF	C0009402	Colorectal Carcinoma	8	CTD_human;UNIPROT
Tgene	BRAF	C0028326	Noonan Syndrome	8	CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET
Tgene	BRAF	C0238463	Papillary thyroid carcinoma	8	CTD_human;ORPHANET
Tgene	BRAF	C0040136	Thyroid Neoplasm	6	CGI;CTD_human
Tgene	BRAF	C0151468	Thyroid Gland Follicular Adenoma	6	CTD_human
Tgene	BRAF	C0175704	LEOPARD Syndrome	6	CLINGEN;GENOMICS_ENGLAND
Tgene	BRAF	C0549473	Thyroid carcinoma	6	CGI;CTD_human
Tgene	BRAF	C3150970	NOONAN SYNDROME 7	5	CTD_human;GENOMICS_ENGLAND;UNIPROT
Tgene	BRAF	C0009404	Colorectal Neoplasms	4	CTD_human
Tgene	BRAF	C3150971	LEOPARD SYNDROME 3	4	CTD_human;GENOMICS_ENGLAND;UNIPROT
Tgene	BRAF	C1519086	Pilomyxoid astrocytoma	3	ORPHANET
Tgene	BRAF	C0004565	Melanoma, B16	2	CTD_human
Tgene	BRAF	C0009075	Melanoma, Cloudman S91	2	CTD_human
Tgene	BRAF	C0018598	Melanoma, Harding-Passey	2	CTD_human
Tgene	BRAF	C0023443	Hairy Cell Leukemia	2	CGI;ORPHANET
Tgene	BRAF	C0025205	Melanoma, Experimental	2	CTD_human
Tgene	BRAF	C0033578	Prostatic Neoplasms	2	CTD_human
Tgene	BRAF	C0152013	Adenocarcinoma of lung (disorder)	2	CGI;CTD_human
Tgene	BRAF	C0376358	Malignant neoplasm of prostate	2	CTD_human
Tgene	BRAF	C0587248	Costello syndrome (disorder)	2	CLINGEN;CTD_human
Tgene	BRAF	C3501843	Nonmedullary Thyroid Carcinoma	2	CTD_human
Tgene	BRAF	C3501844	Familial Nonmedullary Thyroid Cancer	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