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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:DRAP1_PTK7

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: DRAP1_PTK7
	KinaseFusionDB ID: KFG1747
	FusionGDB2.0 ID: KFG1747
		Hgene	Tgene
	Gene symbol	DRAP1	PTK7
	Gene ID	10589	5754
	Gene name	DR1 associated protein 1	protein tyrosine kinase 7 (inactive)
	Synonyms	NC2-alpha	CCK-4\|CCK4
	Cytomap	11q13.1	6p21.1
	Type of gene	protein-coding	protein-coding
	Description	dr1-associated corepressornegative co-factor 2-alphanegative cofactor 2 alpha	inactive tyrosine-protein kinase 7PTK7 protein tyrosine kinase 7colon carcinoma kinase 4pseudo tyrosine kinase receptor 7tyrosine-protein kinase-like 7
	Modification date	20240305	20240407
	UniProtAcc	Q14919	Q13308
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000312515, ENST00000376991, ENST00000527119, ENST00000532933,	ENST00000230419, ENST00000349241, ENST00000345201, ENST00000352931, ENST00000481273, ENST00000476760, ENST00000471863,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: DRAP1 [Title/Abstract] AND PTK7 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)

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	DRAP1	GO:0000122	negative regulation of transcription by RNA polymerase II	8670811

Kinase Fusion gene breakpoints across DRAP1 (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 PTK7 (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
CCLE	YD-15	DRAP1	chr11	65688869	PTK7	chr6	43128548

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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)
ENST00000312515	ENST00000349241	DRAP1	chr11	65688869	PTK7	chr6	43128548	1822	214

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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

>ENST00000312515_ENST00000349241_DRAP1_chr11_65688869_PTK7_chr6_43128548_length(amino acids)=214
MAWGGGCDVSSSPSVSVSSDSSSCSESVPDSFLSLLFVPIPPFFRPPLPGFRPLRAPLSPSMWLSSPSPCMSGTDATRSFKKSNCCSSSM
HCFRWDVVMVFAFRDWVTWQAFFNSDSRKSSSAREMMTGTAAATFPISSSVCMIFLIRAGGNRALYFFFLLGISGPLSPRRVQRRRPQPP

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

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/chr11:/chr6:)
- 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
DRAP1 Q14919	PTK7 Q13308
FUNCTION: The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own. {ECO:0000269\|PubMed:8608938, ECO:0000269\|PubMed:8670811}.	FUNCTION: Inactive tyrosine kinase involved in Wnt signaling pathway. Component of both the non-canonical (also known as the Wnt/planar cell polarity signaling) and the canonical Wnt signaling pathway. Functions in cell adhesion, cell migration, cell polarity, proliferation, actin cytoskeleton reorganization and apoptosis. Has a role in embryogenesis, epithelial tissue organization and angiogenesis. {ECO:0000269\|PubMed:18471990, ECO:0000269\|PubMed:20558616, ECO:0000269\|PubMed:20837484, ECO:0000269\|PubMed:21103379, ECO:0000269\|PubMed:21132015}.

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	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	17	31_120	0	941	Domain	Note=Ig-like C2-type 1
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	31_120	0	1015	Domain	Note=Ig-like C2-type 1
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	31_120	0	1031	Domain	Note=Ig-like C2-type 1
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	31_120	0	1071	Domain	Note=Ig-like C2-type 1
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	31_120	0	1079	Domain	Note=Ig-like C2-type 1
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	17	128_218	0	941	Domain	Note=Ig-like C2-type 2
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	128_218	0	1015	Domain	Note=Ig-like C2-type 2
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	128_218	0	1031	Domain	Note=Ig-like C2-type 2
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	128_218	0	1071	Domain	Note=Ig-like C2-type 2
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	128_218	0	1079	Domain	Note=Ig-like C2-type 2
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	17	225_317	0	941	Domain	Note=Ig-like C2-type 3
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	225_317	0	1015	Domain	Note=Ig-like C2-type 3
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	225_317	0	1031	Domain	Note=Ig-like C2-type 3
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	225_317	0	1071	Domain	Note=Ig-like C2-type 3
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	225_317	0	1079	Domain	Note=Ig-like C2-type 3
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	17	309_407	0	941	Domain	Note=Ig-like C2-type 4
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	309_407	0	1015	Domain	Note=Ig-like C2-type 4
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	309_407	0	1031	Domain	Note=Ig-like C2-type 4
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	309_407	0	1071	Domain	Note=Ig-like C2-type 4
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	309_407	0	1079	Domain	Note=Ig-like C2-type 4
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	17	412_497	0	941	Domain	Note=Ig-like C2-type 5
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	412_497	0	1015	Domain	Note=Ig-like C2-type 5
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	412_497	0	1031	Domain	Note=Ig-like C2-type 5
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	412_497	0	1071	Domain	Note=Ig-like C2-type 5
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	412_497	0	1079	Domain	Note=Ig-like C2-type 5
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	17	503_586	0	941	Domain	Note=Ig-like C2-type 6
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	503_586	0	1015	Domain	Note=Ig-like C2-type 6
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	503_586	0	1031	Domain	Note=Ig-like C2-type 6
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	503_586	0	1071	Domain	Note=Ig-like C2-type 6
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	503_586	0	1079	Domain	Note=Ig-like C2-type 6
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	17	578_680	0	941	Domain	Note=Ig-like C2-type 7
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	578_680	0	1015	Domain	Note=Ig-like C2-type 7
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	578_680	0	1031	Domain	Note=Ig-like C2-type 7
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	578_680	0	1071	Domain	Note=Ig-like C2-type 7
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	578_680	0	1079	Domain	Note=Ig-like C2-type 7
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	17	796_1066	0	941	Domain	Note=Protein kinase%3B inactive;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	796_1066	0	1015	Domain	Note=Protein kinase%3B inactive;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	19	796_1066	0	1031	Domain	Note=Protein kinase%3B inactive;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	796_1066	0	1071	Domain	Note=Protein kinase%3B inactive;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	DRAP1	65688869	PTK7	43128548	ENST00000312515	0	20	796_1066	0	1079	Domain	Note=Protein kinase%3B inactive;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 >>>148_DRAP1_PTK7	ENST00000312515	ENST00000349241	DRAP1	chr11	65688869	PTK7	chr6	43128548	MAWGGGCDVSSSPSVSVSSDSSSCSESVPDSFLSLLFVPIPPFFRPPLPGFRPLRAPLSPSMWLSSPSPCMSGTDATRSFKKSNCCSSSM HCFRWDVVMVFAFRDWVTWQAFFNSDSRKSSSAREMMTGTAAATFPISSSVCMIFLIRAGGNRALYFFFLLGISGPLSPRRVQRRRPQPP	214
3D view using mol* of 148_DRAP1_PTK7

PDB file >>>TKFP_241_DRAP1_PTK7	ENST00000312515	ENST00000349241	DRAP1	chr11	65688869	PTK7	chr6	43128548	MAWGGGCDVSSSPSVSVSSDSSSCSESVPDSFLSLLFVPIPPFFRPPLPGFRPLRAPLSPSMWLSSPSPCMSGTDATRSFKKSNCCSSSM HCFRWDVVMVFAFRDWVTWQAFFNSDSRKSSSAREMMTGTAAATFPISSSVCMIFLIRAGGNRALYFFFLLGISGPLSPRRVQRRRPQPP	214_DRAP1_PTK7

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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

DRAP1_PTK7 does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/148_DRAP1_PTK7.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.

148_DRAP1_PTK7.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.

148_DRAP1_PTK7_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
148_DRAP1_PTK7-DOCK_HTVS_1-001	Gilteritinib	-6.7614600000000005	-6.78786	-45.3753
148_DRAP1_PTK7-DOCK_HTVS_1-001	Gilteritinib	-6.7614600000000005	-6.78786	-45.3753
148_DRAP1_PTK7-DOCK_HTVS_1-001	Netarsudil	-6.55812	-6.56922	-46.2623
148_DRAP1_PTK7-DOCK_HTVS_1-001	Netarsudil	-6.55812	-6.56922	-46.2623
148_DRAP1_PTK7-DOCK_HTVS_1-001	Netarsudil	-6.553889999999999	-6.564989999999999	-43.8581
148_DRAP1_PTK7-DOCK_HTVS_1-001	Netarsudil	-6.553889999999999	-6.564989999999999	-43.8581
148_DRAP1_PTK7-DOCK_HTVS_1-001	Tepotinib	-6.29662	-6.29772	-43.0294
148_DRAP1_PTK7-DOCK_HTVS_1-001	Encorafenib	-6.29082	-6.67932	-44.3793
148_DRAP1_PTK7-DOCK_HTVS_1-001	Abemaciclib	-6.24011	-6.44221	-42.0404
148_DRAP1_PTK7-DOCK_HTVS_1-001	Abemaciclib	-6.24011	-6.44221	-42.0404
148_DRAP1_PTK7-DOCK_HTVS_1-001	Abemaciclib	-6.24011	-6.44221	-42.0404
148_DRAP1_PTK7-DOCK_HTVS_1-001	Abemaciclib	-6.24011	-6.44221	-42.0404
148_DRAP1_PTK7-DOCK_HTVS_1-001	Encorafenib	-6.20777	-6.59627	-43.827
148_DRAP1_PTK7-DOCK_HTVS_1-001	Midostaurin	-5.94931	-5.94931	-34.5863
148_DRAP1_PTK7-DOCK_HTVS_1-001	Mobocertinib	-5.92959	-5.93729	-47.748999999999995
148_DRAP1_PTK7-DOCK_HTVS_1-001	Ruxolitinib	-5.90941	-5.90941	-26.6248
148_DRAP1_PTK7-DOCK_HTVS_1-001	Cobimetinib	-5.89613	-5.89893	-37.037
148_DRAP1_PTK7-DOCK_HTVS_1-001	Upadacitinib	-5.67621	-5.67721	-27.0531
148_DRAP1_PTK7-DOCK_HTVS_1-001	Tofacitinib	-5.6721900000000005	-5.68369	-28.2983
148_DRAP1_PTK7-DOCK_HTVS_1-001	Tofacitinib	-5.6721900000000005	-5.68369	-28.2983

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Kinase-Substrate Information of DRAP1_PTK7

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

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

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Related Drugs to DRAP1_PTK7

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 DRAP1-PTK7 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 DRAP1_PTK7

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

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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