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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein Structure
	pLDDT scores
	Ramachandran Plot of Fusion Protein Structure
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:PARP1-LIN9

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: PARP1-LIN9
	FusionPDB ID: 62822
	FusionGDB2.0 ID: 62822
		Hgene	Tgene
	Gene symbol	PARP1	LIN9
	Gene ID	142	286826
	Gene name	poly(ADP-ribose) polymerase 1	lin-9 DREAM MuvB core complex component
	Synonyms	ADPRT\|ADPRT 1\|ADPRT1\|ARTD1\|PARP\|PARP-1\|PPOL\|pADPRT-1	BARA\|BARPsv\|Lin-9\|TGS\|TGS1\|TGS2
	Cytomap	1q42.12	1q42.12
	Type of gene	protein-coding	protein-coding
	Description	poly [ADP-ribose] polymerase 1ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase)ADP-ribosyltransferase NAD(+)ADP-ribosyltransferase diphtheria toxin-like 1DNA ADP-ribosyltransferase PARP1NAD(+) ADP-ribosyltransferase 1poly (ADP-ribose) poly	protein lin-9 homologTUDOR gene similar proteinbeta subunit-associated regulator of apoptosislin-9 homologpRB-associated proteinrb related pathway actortype I interferon receptor beta chain-associated protein
	Modification date	20200329	20200313
	UniProtAcc	.	Q5TKA1
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000366794, ENST00000366790, ENST00000366791, ENST00000366792, ENST00000490921,	ENST00000328205, ENST00000366801, ENST00000481685,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	4 X 4 X 2=32	6 X 4 X 5=120
	# samples	4	7
	** MAII score	log2(4/32*10)=0.321928094887362 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0	log2(7/120*10)=-0.777607578663552 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: PARP1 [Title/Abstract] AND LIN9 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	PARP1(226561927)-LIN9(226438620), # samples:2
Anticipated loss of major functional domain due to fusion event.	PARP1-LIN9 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. PARP1-LIN9 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. PARP1-LIN9 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. PARP1-LIN9 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.

* 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	PARP1	GO:0006471	protein ADP-ribosylation	7852410\|17396150\|26344098\|27067600
Hgene	PARP1	GO:0006915	apoptotic process	15565177
Hgene	PARP1	GO:0018312	peptidyl-serine ADP-ribosylation	28190768
Hgene	PARP1	GO:0018424	peptidyl-glutamic acid poly-ADP-ribosylation	19764761
Hgene	PARP1	GO:0030592	DNA ADP-ribosylation	27471034
Hgene	PARP1	GO:0032869	cellular response to insulin stimulus	19303849
Hgene	PARP1	GO:0045944	positive regulation of transcription by RNA polymerase II	11112786
Hgene	PARP1	GO:0050790	regulation of catalytic activity	25749521
Hgene	PARP1	GO:0070212	protein poly-ADP-ribosylation	15674325\|19470756\|25043379
Hgene	PARP1	GO:0070213	protein auto-ADP-ribosylation	19764761
Hgene	PARP1	GO:1905168	positive regulation of double-strand break repair via homologous recombination	26344098\|30356214
Hgene	PARP1	GO:1990966	ATP generation from poly-ADP-D-ribose	27257257

Fusion gene breakpoints across PARP1 (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 LIN9 (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 Gene Sample Information

Fusion gene information from FusionGDB2.0.

Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	HNSC	TCGA-CQ-5332-01A	PARP1	chr1	226561927	-	LIN9	chr1	226438620	-
ChimerDB4	HNSC	TCGA-CQ-5332	PARP1	chr1	226561927	-	LIN9	chr1	226438620	-

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Fusion ORF Analysis

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)
ENST00000366794	PARP1	chr1	226561927	-	ENST00000328205	LIN9	chr1	226438620	-	4149	2214	144	2804	886
ENST00000366794	PARP1	chr1	226561927	-	ENST00000366801	LIN9	chr1	226438620	-	4142	2214	144	2804	886
ENST00000366794	PARP1	chr1	226561927	-	ENST00000481685	LIN9	chr1	226438620	-	3082	2214	144	2702	852

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
ENST00000366794	ENST00000328205	PARP1	chr1	226561927	-	LIN9	chr1	226438620	-	0.000531293	0.99946874
ENST00000366794	ENST00000366801	PARP1	chr1	226561927	-	LIN9	chr1	226438620	-	0.000530681	0.99946934
ENST00000366794	ENST00000481685	PARP1	chr1	226561927	-	LIN9	chr1	226438620	-	0.003627148	0.99637294

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Fusion Amino Acid Sequences

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

>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>62822_62822_1_PARP1-LIN9_PARP1_chr1_226561927_ENST00000366794_LIN9_chr1_226438620_ENST00000328205_length(amino acids)=886AA_BP=0
MAESSDKLYRVEYAKSGRASCKKCSESIPKDSLRMAIMVQSPMFDGKVPHWYHFSCFWKVGHSIRHPDVEVDGFSELRWDDQQKVKKTAE
AGGVTGKGQDGIGSKAEKTLGDFAAEYAKSNRSTCKGCMEKIEKGQVRLSKKMVDPEKPQLGMIDRWYHPGCFVKNREELGFRPEYSASQ
LKGFSLLATEDKEALKKQLPGVKSEGKRKGDEVDGVDEVAKKKSKKEKDKDSKLEKALKAQNDLIWNIKDELKKVCSTNDLKELLIFNKQ
QVPSGESAILDRVADGMVFGALLPCEECSGQLVFKSDAYYCTGDVTAWTKCMVKTQTPNRKEWVTPKEFREISYLKKLKVKKQDRIFPPE
TSASVAATPPPSTASAPAAVNSSASADKPLSNMKILTLGKLSRNKDEVKAMIEKLGGKLTGTANKASLCISTKKEVEKMNKKMEEVKEAN
IRVVSEDFLQDVSASTKSLQELFLAHILSPWGAEVKAEPVEVVAPRGKSGAALSKKSKGQVKEEGINKSEKRMKLTLKGGAAVDPDSGLE
HSAHVLEKGGKVFSATLGLVDIVKGTNSYYKLQLLEDDKENRYWIFRSWGRVGTVIGSNKLEQMPSKEDAIEHFMKLYEEKTGNAWHSKN
FTKYPKKFYPLEIDYGQDEEAVKKLTVNPGTKSKLPKPVQDLIKMIFDVESMKKAMVEYETRLSKILMIKKEHIKKLREMNTEAEKLKSY
SMPISIEFQRRYATIVLELEQLNKDLNKVLHKVQQYCYELAPDQGLQPADQPTDMRRRCEEEAQEIVRHANSSTGQPCVENENLTDLISR

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

>62822_62822_2_PARP1-LIN9_PARP1_chr1_226561927_ENST00000366794_LIN9_chr1_226438620_ENST00000366801_length(amino acids)=886AA_BP=0
MAESSDKLYRVEYAKSGRASCKKCSESIPKDSLRMAIMVQSPMFDGKVPHWYHFSCFWKVGHSIRHPDVEVDGFSELRWDDQQKVKKTAE
AGGVTGKGQDGIGSKAEKTLGDFAAEYAKSNRSTCKGCMEKIEKGQVRLSKKMVDPEKPQLGMIDRWYHPGCFVKNREELGFRPEYSASQ
LKGFSLLATEDKEALKKQLPGVKSEGKRKGDEVDGVDEVAKKKSKKEKDKDSKLEKALKAQNDLIWNIKDELKKVCSTNDLKELLIFNKQ
QVPSGESAILDRVADGMVFGALLPCEECSGQLVFKSDAYYCTGDVTAWTKCMVKTQTPNRKEWVTPKEFREISYLKKLKVKKQDRIFPPE
TSASVAATPPPSTASAPAAVNSSASADKPLSNMKILTLGKLSRNKDEVKAMIEKLGGKLTGTANKASLCISTKKEVEKMNKKMEEVKEAN
IRVVSEDFLQDVSASTKSLQELFLAHILSPWGAEVKAEPVEVVAPRGKSGAALSKKSKGQVKEEGINKSEKRMKLTLKGGAAVDPDSGLE
HSAHVLEKGGKVFSATLGLVDIVKGTNSYYKLQLLEDDKENRYWIFRSWGRVGTVIGSNKLEQMPSKEDAIEHFMKLYEEKTGNAWHSKN
FTKYPKKFYPLEIDYGQDEEAVKKLTVNPGTKSKLPKPVQDLIKMIFDVESMKKAMVEYETRLSKILMIKKEHIKKLREMNTEAEKLKSY
SMPISIEFQRRYATIVLELEQLNKDLNKVLHKVQQYCYELAPDQGLQPADQPTDMRRRCEEEAQEIVRHANSSTGQPCVENENLTDLISR

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

>62822_62822_3_PARP1-LIN9_PARP1_chr1_226561927_ENST00000366794_LIN9_chr1_226438620_ENST00000481685_length(amino acids)=852AA_BP=0
MAESSDKLYRVEYAKSGRASCKKCSESIPKDSLRMAIMVQSPMFDGKVPHWYHFSCFWKVGHSIRHPDVEVDGFSELRWDDQQKVKKTAE
AGGVTGKGQDGIGSKAEKTLGDFAAEYAKSNRSTCKGCMEKIEKGQVRLSKKMVDPEKPQLGMIDRWYHPGCFVKNREELGFRPEYSASQ
LKGFSLLATEDKEALKKQLPGVKSEGKRKGDEVDGVDEVAKKKSKKEKDKDSKLEKALKAQNDLIWNIKDELKKVCSTNDLKELLIFNKQ
QVPSGESAILDRVADGMVFGALLPCEECSGQLVFKSDAYYCTGDVTAWTKCMVKTQTPNRKEWVTPKEFREISYLKKLKVKKQDRIFPPE
TSASVAATPPPSTASAPAAVNSSASADKPLSNMKILTLGKLSRNKDEVKAMIEKLGGKLTGTANKASLCISTKKEVEKMNKKMEEVKEAN
IRVVSEDFLQDVSASTKSLQELFLAHILSPWGAEVKAEPVEVVAPRGKSGAALSKKSKGQVKEEGINKSEKRMKLTLKGGAAVDPDSGLE
HSAHVLEKGGKVFSATLGLVDIVKGTNSYYKLQLLEDDKENRYWIFRSWGRVGTVIGSNKLEQMPSKEDAIEHFMKLYEEKTGNAWHSKN
FTKYPKKFYPLEIDYGQDEEAVKKLTVNPGTKSKLPKPVQDLIKMIFDVESMKKAMVEYETRLSKILMIKKEHIKKLREMNTEAEKLKSY
SMPISIEFQRRYATIVLELEQLNKDLNKVLHKVQQYCYELAPDQGLQPADQPTDMRRRCEEEAQEIVRHANSSTGQPCVENENLTDLISR

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

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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/chr1:226561927/chr1:226438620)
- 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
.	LIN9 Q5TKA1
FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.	FUNCTION: Acts as a tumor suppressor. Inhibits DNA synthesis. Its ability to inhibit oncogenic transformation is mediated through its association with RB1. Plays a role in the expression of genes required for the G1/S transition. {ECO:0000269\|PubMed:15538385, ECO:0000269\|PubMed:16730350}.

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 protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

385_476

690.0

1015.0

Domain

BRCT

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

554_630

690.0

1015.0

Domain

WGR

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

207_209

690.0

1015.0

Motif

Nuclear localization signal

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

221_226

690.0

1015.0

Motif

Nuclear localization signal

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

198_233

690.0

1015.0

Region

Disordered

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

355_386

690.0

1015.0

Region

Disordered

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

373_524

690.0

1015.0

Region

Automodification domain

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

113_203

690.0

1015.0

Zinc finger

PARP-type 2

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

9_93

690.0

1015.0

Zinc finger

PARP-type 1

Tgene

LIN9

chr1:226561927

chr1:226438620

ENST00000366801

354_413

311.0

508.0

Coiled coil

Ontology_term=ECO:0000255

- Not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

662_779

690.0

1015.0

Domain

PARP alpha-helical

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

788_1014

690.0

1015.0

Domain

PARP catalytic

Hgene

PARP1

chr1:226561927

chr1:226438620

ENST00000366794

862_864

690.0

1015.0

Nucleotide binding

NAD

Tgene

LIN9

chr1:226561927

chr1:226438620

ENST00000328205

354_413

362.0

559.0

Coiled coil

Ontology_term=ECO:0000255

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Fusion Protein Structures

PDB and CIF files of the predicted 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.

Fusion protein PDB link (fusion AA seq ID in FusionPDB)	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	AA seq	Len(AA seq)
PDB file >>>1674_PARP1_226561927_LIN9_226438620_ranked_0.pdb	PARP1	226561927	226561927	ENST00000481685	LIN9	chr1	226438620	-	MAESSDKLYRVEYAKSGRASCKKCSESIPKDSLRMAIMVQSPMFDGKVPHWYHFSCFWKVGHSIRHPDVEVDGFSELRWDDQQKVKKTAE AGGVTGKGQDGIGSKAEKTLGDFAAEYAKSNRSTCKGCMEKIEKGQVRLSKKMVDPEKPQLGMIDRWYHPGCFVKNREELGFRPEYSASQ LKGFSLLATEDKEALKKQLPGVKSEGKRKGDEVDGVDEVAKKKSKKEKDKDSKLEKALKAQNDLIWNIKDELKKVCSTNDLKELLIFNKQ QVPSGESAILDRVADGMVFGALLPCEECSGQLVFKSDAYYCTGDVTAWTKCMVKTQTPNRKEWVTPKEFREISYLKKLKVKKQDRIFPPE TSASVAATPPPSTASAPAAVNSSASADKPLSNMKILTLGKLSRNKDEVKAMIEKLGGKLTGTANKASLCISTKKEVEKMNKKMEEVKEAN IRVVSEDFLQDVSASTKSLQELFLAHILSPWGAEVKAEPVEVVAPRGKSGAALSKKSKGQVKEEGINKSEKRMKLTLKGGAAVDPDSGLE HSAHVLEKGGKVFSATLGLVDIVKGTNSYYKLQLLEDDKENRYWIFRSWGRVGTVIGSNKLEQMPSKEDAIEHFMKLYEEKTGNAWHSKN FTKYPKKFYPLEIDYGQDEEAVKKLTVNPGTKSKLPKPVQDLIKMIFDVESMKKAMVEYETRLSKILMIKKEHIKKLREMNTEAEKLKSY SMPISIEFQRRYATIVLELEQLNKDLNKVLHKVQQYCYELAPDQGLQPADQPTDMRRRCEEEAQEIVRHANSSTGQPCVENENLTDLISR	886

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pLDDT score distribution

pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

PARP1_pLDDT.png

LIN9_pLDDT.png

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

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Ramachandran Plot of 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.

Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Fusion Protein-Protein Interaction

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)

Gene

PPI interactors

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
PARP1
LIN9

- Retained interactions in fusion protein (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost interactions due to fusion (protein functional feature from UniProt).

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs to PARP1-LIN9

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 PARP1-LIN9

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