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Fusion Protein:PKN1-LDLR

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: PKN1-LDLR
	FusionPDB ID: 65773
	FusionGDB2.0 ID: 65773
		Hgene	Tgene
	Gene symbol	PKN1	LDLR
	Gene ID	5585	3949
	Gene name	protein kinase N1	low density lipoprotein receptor
	Synonyms	DBK\|PAK-1\|PAK1\|PKN\|PKN-ALPHA\|PRK1\|PRKCL1	FH\|FHC\|FHCL1\|LDLCQ2
	Cytomap	19p13.12	19p13.2
	Type of gene	protein-coding	protein-coding
	Description	serine/threonine-protein kinase N1protease-activated kinase 1protein kinase C-like 1protein kinase C-like PKNprotein kinase C-related kinase 1protein kinase PKN-alphaserine-threonine kinase Nserine/threonine protein kinase N	low-density lipoprotein receptorLDL receptorlow-density lipoprotein receptor class A domain-containing protein 3
	Modification date	20200329	20200322
	UniProtAcc	.	Q5SW96 Main function of 5'-partner protein: FUNCTION: Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Required for trafficking of LRP2 to the endocytic recycling compartment which is necessary for LRP2 proteolysis, releasing a tail fragment which translocates to the nucleus and mediates transcriptional repression (By similarity). {ECO:0000250\|UniProtKB:D3ZAR1, ECO:0000269\|PubMed:15728179}.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000242783, ENST00000342216, ENST00000587429,	ENST00000560628, ENST00000455727, ENST00000535915, ENST00000545707, ENST00000557933, ENST00000558013, ENST00000558518,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	10 X 7 X 8=560	4 X 6 X 4=96
	# samples	12	5
	** MAII score	log2(12/560*10)=-2.22239242133645 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(5/96*10)=-0.941106310946431 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: PKN1 [Title/Abstract] AND LDLR [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: PKN1 [Title/Abstract] AND LDLR [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	PKN1(14557373)-LDLR(11227535), # samples:2
Anticipated loss of major functional domain due to fusion event.	PKN1-LDLR seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. PKN1-LDLR seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. PKN1-LDLR seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. PKN1-LDLR seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. PKN1-LDLR seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. PKN1-LDLR seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. PKN1-LDLR seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. PKN1-LDLR seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF. PKN1-LDLR seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.

* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

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	PKN1	GO:0006357	regulation of transcription by RNA polymerase II	12514133
Hgene	PKN1	GO:0006468	protein phosphorylation	17332740
Hgene	PKN1	GO:0035407	histone H3-T11 phosphorylation	18066052

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:14557373/chr19:11227535)
- 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.

Retention analysis results 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, are available here.

Fusion gene breakpoints across PKN1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across LDLR (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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Fusion Amino Acid Sequences

Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	Seq length (transcript)	BP loci (transcript)	Predicted start (transcript)	Predicted stop (transcript)	Seq length (amino acids)
ENST00000242783	PKN1	chr19	14557373	+	ENST00000558518	LDLR	chr19	11227535	+	2500	775	165	1652	495
ENST00000242783	PKN1	chr19	14557373	+	ENST00000557933	LDLR	chr19	11227535	+	1924	775	165	1916	583
ENST00000242783	PKN1	chr19	14557373	+	ENST00000455727	LDLR	chr19	11227535	+	1821	775	165	1652	495
ENST00000242783	PKN1	chr19	14557373	+	ENST00000535915	LDLR	chr19	11227535	+	1875	775	165	1652	495
ENST00000242783	PKN1	chr19	14557373	+	ENST00000545707	LDLR	chr19	11227535	+	1794	775	165	1499	444
ENST00000242783	PKN1	chr19	14557373	+	ENST00000558013	LDLR	chr19	11227535	+	2143	775	165	1646	493
ENST00000342216	PKN1	chr19	14557373	+	ENST00000558518	LDLR	chr19	11227535	+	2384	659	31	1536	501
ENST00000342216	PKN1	chr19	14557373	+	ENST00000557933	LDLR	chr19	11227535	+	1808	659	31	1800	589
ENST00000342216	PKN1	chr19	14557373	+	ENST00000455727	LDLR	chr19	11227535	+	1705	659	31	1536	501
ENST00000342216	PKN1	chr19	14557373	+	ENST00000535915	LDLR	chr19	11227535	+	1759	659	31	1536	501
ENST00000342216	PKN1	chr19	14557373	+	ENST00000545707	LDLR	chr19	11227535	+	1678	659	31	1383	450
ENST00000342216	PKN1	chr19	14557373	+	ENST00000558013	LDLR	chr19	11227535	+	2027	659	31	1530	499

DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	No-coding score	Coding score
ENST00000242783	ENST00000558518	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.022305634	0.9776944
ENST00000242783	ENST00000557933	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.10431041	0.8956896
ENST00000242783	ENST00000455727	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.025160855	0.97483915
ENST00000242783	ENST00000535915	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.026398083	0.97360194
ENST00000242783	ENST00000545707	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.012469866	0.9875301
ENST00000242783	ENST00000558013	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.022939015	0.977061
ENST00000342216	ENST00000558518	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.04011812	0.95988184
ENST00000342216	ENST00000557933	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.11569983	0.88430023
ENST00000342216	ENST00000455727	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.038374744	0.9616252
ENST00000342216	ENST00000535915	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.04130113	0.9586988
ENST00000342216	ENST00000545707	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.021241404	0.9787586
ENST00000342216	ENST00000558013	PKN1	chr19	14557373	+	LDLR	chr19	11227535	+	0.033702962	0.96629703

Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for PKN1-LDLR

+/-13 AA sequence from the breakpoints of the fusion protein sequences.

Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Length(fusion protein)	BP in fusion protein	Peptide
PKN1	chr19	14557373	LDLR	chr19	11227535	659	209	GQLENQAAPDDTQDLLSGRLYWVDSK
PKN1	chr19	14557373	LDLR	chr19	11227535	775	203	GQLENQAAPDDTQDLLSGRLYWVDSK

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Potential FusionNeoAntigen Information of PKN1-LDLR in HLA I

Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

PKN1-LDLR_14557373_11227535.msa

Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)

Fusion gene	Hchr	Hbp	Tgene	Tchr	Tbp	HLA I	FusionNeoAntigen peptide	Binding score	Immunogenic score	Neoantigen start (at BP 13)	Neoantigen end (at BP 13)
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A66:01	DTQDLLSGR	0.9983	0.553	10	19
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A26:03	DTQDLLSGR	0.9916	0.5465	10	19
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B44:03	QDLLSGRLY	0.9399	0.8416	12	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:03	APDDTQDLL	0.8432	0.9728	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A68:08	DTQDLLSGR	0.8368	0.5094	10	19
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:08	APDDTQDLL	0.8282	0.9659	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B07:05	APDDTQDLL	0.8003	0.598	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:13	TQDLLSGRL	0.7098	0.915	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B38:01	TQDLLSGRL	0.6888	0.9518	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:02	APDDTQDLL	0.5777	0.982	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:04	APDDTQDLL	0.5777	0.982	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B13:01	TQDLLSGRL	0.4506	0.9571	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B81:01	APDDTQDLL	0.1975	0.6209	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B82:01	APDDTQDLL	0.1136	0.5119	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B44:02	QDLLSGRLYW	0.997	0.6148	12	22
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:01	TQDLLSGRLY	0.9955	0.5661	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:25	TQDLLSGRLY	0.9786	0.6567	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A32:13	QDLLSGRLYW	0.9371	0.903	12	22
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A66:01	DDTQDLLSGR	0.8788	0.6447	9	19
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A68:24	DDTQDLLSGR	0.8433	0.663	9	19
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A68:03	DDTQDLLSGR	0.8312	0.6264	9	19
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A68:05	DDTQDLLSGR	0.7998	0.635	9	19
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A32:13	TQDLLSGRLYW	0.9941	0.9148	11	22
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:04	QAAPDDTQDLL	0.9784	0.9883	5	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:02	QAAPDDTQDLL	0.9784	0.9883	5	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:10	APDDTQDL	0.5343	0.9597	7	15
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C05:09	TQDLLSGRL	0.9998	0.8881	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:15	TQDLLSGRL	0.9996	0.9763	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C05:09	APDDTQDLL	0.9969	0.9818	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C04:10	APDDTQDLL	0.9962	0.8615	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C04:07	APDDTQDLL	0.996	0.8965	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:15	APDDTQDLL	0.99	0.9853	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C01:17	AAPDDTQDL	0.9558	0.9817	6	15
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:09	TQDLLSGRL	0.8104	0.7493	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B07:12	APDDTQDLL	0.7826	0.7884	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C01:30	AAPDDTQDL	0.7662	0.9785	6	15
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:08	TQDLLSGRL	0.757	0.9033	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:05	TQDLLSGRL	0.6835	0.894	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:12	APDDTQDLL	0.5777	0.982	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:08	APDDTQDLL	0.4786	0.9709	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:09	APDDTQDLL	0.4741	0.9161	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:10	APDDTQDLL	0.469	0.971	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:03	APDDTQDLL	0.4384	0.9827	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C04:14	APDDTQDLL	0.3972	0.8404	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C05:09	AAPDDTQDLL	0.9994	0.9822	6	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:15	AAPDDTQDLL	0.9981	0.9863	6	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B44:08	QDLLSGRLYW	0.994	0.7772	12	22
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C01:17	AAPDDTQDLL	0.9919	0.9721	6	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:05	TQDLLSGRLY	0.9798	0.5959	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A68:01	DDTQDLLSGR	0.8433	0.663	9	19
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A33:03	DDTQDLLSGR	0.7717	0.5535	9	19
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:15	QAAPDDTQDLL	0.9999	0.9793	5	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B44:08	TQDLLSGRLYW	0.9984	0.8235	11	22
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:12	QAAPDDTQDLL	0.9784	0.9883	5	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C04:03	TQDLLSGRL	0.9998	0.9163	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C05:01	TQDLLSGRL	0.9998	0.8881	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:02	TQDLLSGRL	0.9996	0.9763	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C05:01	APDDTQDLL	0.9969	0.9818	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C04:03	APDDTQDLL	0.9966	0.9272	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C04:01	APDDTQDLL	0.996	0.8965	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C18:01	APDDTQDLL	0.991	0.8942	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:02	APDDTQDLL	0.99	0.9853	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C01:03	AAPDDTQDL	0.9713	0.9797	6	15
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C01:02	AAPDDTQDL	0.9606	0.9808	6	15
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B44:26	QDLLSGRLY	0.9399	0.8416	12	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B44:07	QDLLSGRLY	0.9399	0.8416	12	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B44:13	QDLLSGRLY	0.9399	0.8416	12	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C03:06	AAPDDTQDL	0.8964	0.9931	6	15
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:02	TQDLLSGRL	0.8274	0.9073	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:13	APDDTQDLL	0.7916	0.974	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:11	TQDLLSGRL	0.7074	0.8894	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B38:05	TQDLLSGRL	0.6888	0.9518	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:09	APDDTQDLL	0.5777	0.982	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B67:01	APDDTQDLL	0.5011	0.9268	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B39:11	APDDTQDLL	0.4865	0.9299	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:01	APDDTQDLL	0.4384	0.9827	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:09	TQDLLSGRL	0.374	0.8368	11	20
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B82:02	APDDTQDLL	0.1136	0.5119	7	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C05:01	AAPDDTQDLL	0.9994	0.9822	6	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C04:03	AAPDDTQDLL	0.9993	0.925	6	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:02	AAPDDTQDLL	0.9981	0.9863	6	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C01:03	AAPDDTQDLL	0.9981	0.9688	6	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B44:22	QDLLSGRLYW	0.997	0.6148	12	22
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B44:21	QDLLSGRLYW	0.9964	0.5775	12	22
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:125	TQDLLSGRLY	0.9955	0.5661	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:34	TQDLLSGRLY	0.9955	0.5661	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:33	TQDLLSGRLY	0.9955	0.5661	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:135	TQDLLSGRLY	0.9952	0.5869	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C01:02	AAPDDTQDLL	0.9949	0.9709	6	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:50	TQDLLSGRLY	0.9939	0.7539	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:12	TQDLLSGRLY	0.9937	0.5042	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:53	TQDLLSGRLY	0.9867	0.5378	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:20	TQDLLSGRLY	0.9812	0.712	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:39	TQDLLSGRLY	0.981	0.5088	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:28	TQDLLSGRLY	0.9727	0.7642	11	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A32:01	QDLLSGRLYW	0.9249	0.9415	12	22
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-C08:02	QAAPDDTQDLL	0.9999	0.9793	5	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-A25:01	DTQDLLSGRLY	0.9974	0.616	10	21
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B15:24	TQDLLSGRLYW	0.9954	0.9504	11	22
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B51:05	QAAPDDTQDLL	0.9916	0.5825	5	16
PKN1-LDLR	chr19	14557373	chr19	11227535	775	HLA-B35:09	QAAPDDTQDLL	0.9784	0.9883	5	16

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Potential FusionNeoAntigen Information of PKN1-LDLR in HLA II

Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA II

FusionNeoAntigen peptide

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of PKN1-LDLR

3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

File name	BPseq	Hgene	Tgene	Hchr	Hbp	Tchr	Tbp	AAlen
59	AAPDDTQDLLSGRL	PKN1	LDLR	chr19	14557373	chr19	11227535	775

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PKN1-LDLR

Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.

HLA allele	PDB ID	File name	BPseq	Docking score	Glide score
HLA-B14:02	3BVN	59	AAPDDTQDLLSGRL	-7.9953	-8.11
HLA-B14:02	3BVN	59	AAPDDTQDLLSGRL	-6.76387	-7.80047
HLA-B52:01	3W39	59	AAPDDTQDLLSGRL	-6.72115	-6.83585
HLA-B52:01	3W39	59	AAPDDTQDLLSGRL	-4.59437	-5.63097
HLA-A24:02	5HGA	59	AAPDDTQDLLSGRL	-8.73414	-8.84884
HLA-A24:02	5HGA	59	AAPDDTQDLLSGRL	-6.32039	-7.35699
HLA-B44:05	3DX8	59	AAPDDTQDLLSGRL	-5.20472	-5.31942
HLA-B44:05	3DX8	59	AAPDDTQDLLSGRL	-4.80907	-5.84567
HLA-A02:01	6TDR	59	AAPDDTQDLLSGRL	0.647201	-0.389399

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Vaccine Design for the FusionNeoAntigens of PKN1-LDLR

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.

Fusion gene	Hchr	Hbp	Tchr	Tbp	Start in +/-13AA	End in +/-13AA	FusionNeoAntigen peptide sequence	FusionNeoAntigen RNA sequence
PKN1-LDLR	chr19	14557373	chr19	11227535	10	19	DTQDLLSGR	ACACCCAAGATCTCCTCAGTGGCCGCC
PKN1-LDLR	chr19	14557373	chr19	11227535	10	21	DTQDLLSGRLY	ACACCCAAGATCTCCTCAGTGGCCGCCTCTACT
PKN1-LDLR	chr19	14557373	chr19	11227535	11	20	TQDLLSGRL	CCCAAGATCTCCTCAGTGGCCGCCTCT
PKN1-LDLR	chr19	14557373	chr19	11227535	11	21	TQDLLSGRLY	CCCAAGATCTCCTCAGTGGCCGCCTCTACT
PKN1-LDLR	chr19	14557373	chr19	11227535	11	22	TQDLLSGRLYW	CCCAAGATCTCCTCAGTGGCCGCCTCTACTGGG
PKN1-LDLR	chr19	14557373	chr19	11227535	12	21	QDLLSGRLY	AAGATCTCCTCAGTGGCCGCCTCTACT
PKN1-LDLR	chr19	14557373	chr19	11227535	12	22	QDLLSGRLYW	AAGATCTCCTCAGTGGCCGCCTCTACTGGG
PKN1-LDLR	chr19	14557373	chr19	11227535	5	16	QAAPDDTQDLL	AGGCAGCCCCGGATGACACCCAAGATCTCCTCA
PKN1-LDLR	chr19	14557373	chr19	11227535	6	15	AAPDDTQDL	CAGCCCCGGATGACACCCAAGATCTCC
PKN1-LDLR	chr19	14557373	chr19	11227535	6	16	AAPDDTQDLL	CAGCCCCGGATGACACCCAAGATCTCCTCA
PKN1-LDLR	chr19	14557373	chr19	11227535	7	15	APDDTQDL	CCCCGGATGACACCCAAGATCTCC
PKN1-LDLR	chr19	14557373	chr19	11227535	7	16	APDDTQDLL	CCCCGGATGACACCCAAGATCTCCTCA
PKN1-LDLR	chr19	14557373	chr19	11227535	9	19	DDTQDLLSGR	ATGACACCCAAGATCTCCTCAGTGGCCGCC

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide

FusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of PKN1-LDLR

These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.

Cancer type	Fusion gene	Hchr	Hbp	Henst	Tchr	Tbp	Tenst	Sample
BRCA	PKN1-LDLR	chr19	14557373	ENST00000242783	chr19	11227535	ENST00000455727	TCGA-C8-A26W-01A

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Potential target of CAR-T therapy development for PKN1-LDLR

Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features

* Minus value of BPloci means that the break point is located before the CDS.

- In-frame and retained 'Transmembrane'.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

LDLR

chr19:14557373

chr19:11227535

ENST00000455727

789_810

693.0

Transmembrane

Helical

Tgene

LDLR

chr19:14557373

chr19:11227535

ENST00000535915

789_810

820.0

Transmembrane

Helical

Tgene

LDLR

chr19:14557373

chr19:11227535

ENST00000545707

789_810

683.0

Transmembrane

Helical

Tgene

LDLR

chr19:14557373

chr19:11227535

ENST00000558013

789_810

859.0

Transmembrane

Helical

Tgene

LDLR

chr19:14557373

chr19:11227535

ENST00000558518

789_810

861.0

Transmembrane

Helical

Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.

Hgene

Hchr

Hbp

Henst

Tgene

Tchr

Tbp

Tenst

DeepLoc result

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Related Drugs to PKN1-LDLR

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

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Related Diseases to PKN1-LDLR

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

Hgene

Tgene

Disease

Source

PMID

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source

	Fusion Gene and Fusion Protein Summary
	Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)
	Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)
	Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)
	Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)
	Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)
	Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)
	Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)
	Potential target of CAR-T therapy development
	Information on the samples that have these potential fusion neoantigens
	Fusion Protein Targeting Drugs - (Manual Curation)
	Fusion Protein Related diseases - (Manual Curation)