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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:HNRNPC-WRN

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: HNRNPC-WRN
	FusionPDB ID: 37144
	FusionGDB2.0 ID: 37144
		Hgene	Tgene
	Gene symbol	HNRNPC	WRN
	Gene ID	3183	7486
	Gene name	heterogeneous nuclear ribonucleoprotein C	WRN RecQ like helicase
	Synonyms	C1\|C2\|HNRNP\|HNRPC\|SNRPC	RECQ3\|RECQL2\|RECQL3
	Cytomap	14q11.2	8p12
	Type of gene	protein-coding	protein-coding
	Description	heterogeneous nuclear ribonucleoproteins C1/C2heterogeneous nuclear ribonucleoprotein C (C1/C2)hnRNP C1/C2nuclear ribonucleoprotein particle C1 proteinnuclear ribonucleoprotein particle C2 protein	Werner syndrome ATP-dependent helicaseDNA helicase, RecQ-like type 3Werner syndrome RecQ like helicaseWerner syndrome, RecQ helicase-likeexonuclease WRNrecQ protein-like 2
	Modification date	20200322	20200320
	UniProtAcc	P07910	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000336053, ENST00000420743, ENST00000449098, ENST00000553300, ENST00000553753, ENST00000554455, ENST00000554969, ENST00000555309, ENST00000555883, ENST00000555914, ENST00000556142, ENST00000556513, ENST00000556628, ENST00000557201, ENST00000320084, ENST00000430246, ENST00000556897,	ENST00000298139,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	20 X 19 X 10=3800	9 X 10 X 7=630
	# samples	26	11
	** MAII score	log2(26/3800*10)=-3.86941589018986 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(11/630*10)=-2.51784830486262 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: HNRNPC [Title/Abstract] AND WRN [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	HNRNPC(21698478)-WRN(31030511), # samples:2
Anticipated loss of major functional domain due to fusion event.	HNRNPC-WRN 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. HNRNPC-WRN 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. HNRNPC-WRN 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. HNRNPC-WRN 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. HNRNPC-WRN seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. HNRNPC-WRN seems lost the major protein functional domain in Tgene partner, which is a CGC 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
Tgene	WRN	GO:0000731	DNA synthesis involved in DNA repair	17563354
Tgene	WRN	GO:0006259	DNA metabolic process	16622405
Tgene	WRN	GO:0006284	base-excision repair	17611195
Tgene	WRN	GO:0006974	cellular response to DNA damage stimulus	18203716
Tgene	WRN	GO:0006979	response to oxidative stress	17611195
Tgene	WRN	GO:0009267	cellular response to starvation	11420665
Tgene	WRN	GO:0010225	response to UV-C	17563354
Tgene	WRN	GO:0031297	replication fork processing	17115688
Tgene	WRN	GO:0032508	DNA duplex unwinding	11735402\|26420422
Tgene	WRN	GO:0044806	G-quadruplex DNA unwinding	11735402
Tgene	WRN	GO:0051345	positive regulation of hydrolase activity	17611195
Tgene	WRN	GO:0061820	telomeric D-loop disassembly	15200954\|19734539\|26420422
Tgene	WRN	GO:0071480	cellular response to gamma radiation	21639834
Tgene	WRN	GO:0098530	positive regulation of strand invasion	26420422
Tgene	WRN	GO:1902570	protein localization to nucleolus	11420665

Fusion gene breakpoints across HNRNPC (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 WRN (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	PRAD	TCGA-J9-A8CK-01A	HNRNPC	chr14	21698478	-	WRN	chr8	31030511	+
ChimerDB4	PRAD	TCGA-J9-A8CK	HNRNPC	chr14	21698478	-	WRN	chr8	31030511	+

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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)
ENST00000320084	HNRNPC	chr14	21698478	-	ENST00000298139	WRN	chr8	31030511	+	1419	644	240	716	158
ENST00000430246	HNRNPC	chr14	21698478	-	ENST00000298139	WRN	chr8	31030511	+	4092	3317	2606	3046	146
ENST00000556897	HNRNPC	chr14	21698478	-	ENST00000298139	WRN	chr8	31030511	+	1253	478	113	550	145

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
ENST00000320084	ENST00000298139	HNRNPC	chr14	21698478	-	WRN	chr8	31030511	+	0.0017174	0.9982827
ENST00000430246	ENST00000298139	HNRNPC	chr14	21698478	-	WRN	chr8	31030511	+	0.001688395	0.99831164
ENST00000556897	ENST00000298139	HNRNPC	chr14	21698478	-	WRN	chr8	31030511	+	0.002352457	0.9976476

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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

>37144_37144_1_HNRNPC-WRN_HNRNPC_chr14_21698478_ENST00000320084_WRN_chr8_31030511_ENST00000298139_length(amino acids)=158AA_BP=134
MASNVTNKTDPRSMNSRVFIGNLNTLVVKKSDVEAIFSKYGKIVGCSVHKGFAFVQYVNERNARAAVAGEDGRMIAGQVLDINLAAEPKV

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

>37144_37144_2_HNRNPC-WRN_HNRNPC_chr14_21698478_ENST00000430246_WRN_chr8_31030511_ENST00000298139_length(amino acids)=146AA_BP=
MDVCIFNFFYFCFFIFNLSFVKFLNCAAIKCVWYYLTLMIVMAFSLKAIFLLFPLKSHPAFPVHYPSQTTSCSNMDAQPGAAAARMTWSQ

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

>37144_37144_3_HNRNPC-WRN_HNRNPC_chr14_21698478_ENST00000556897_WRN_chr8_31030511_ENST00000298139_length(amino acids)=145AA_BP=121
MASNVTNKTDPRSMNSRVFIGNLNTLVVKKSDVEAIFSKYGKIVGCSVHKGFAFVQYVNERNARAAVAGEDGRMIAGQVLDINLAAEPKV

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

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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/chr14:21698478/chr8:31030511)
- 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
HNRNPC P07910	.
FUNCTION: Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles (PubMed:8264621). Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules (PubMed:12509468, PubMed:16010978, PubMed:7567451, PubMed:8264621). Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides (PubMed:8264621). May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing (PubMed:25719671). {ECO:0000269\|PubMed:12509468, ECO:0000269\|PubMed:16010978, ECO:0000269\|PubMed:25719671, ECO:0000269\|PubMed:7567451, ECO:0000269\|PubMed:8264621}.	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.

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

HNRNPC

chr14:21698478

chr8:31030511

ENST00000320084

16_87

134.66666666666666

307.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000420743

16_87

134.66666666666666

307.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000430246

16_87

121.66666666666667

294.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000449098

16_87

121.66666666666667

294.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000553300

16_87

121.66666666666667

294.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000554455

16_87

134.66666666666666

307.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000554969

16_87

121.66666666666667

294.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000555883

16_87

121.66666666666667

251.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000556897

16_87

121.66666666666667

294.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000557201

16_87

134.66666666666666

307.0

Domain

RRM

- 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

HNRNPC

chr14:21698478

chr8:31030511

ENST00000320084

190_238

134.66666666666666

307.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000420743

190_238

134.66666666666666

307.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000430246

190_238

121.66666666666667

294.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000449098

190_238

121.66666666666667

294.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000553300

190_238

121.66666666666667

294.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000554455

190_238

134.66666666666666

307.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000554969

190_238

121.66666666666667

294.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000555883

190_238

121.66666666666667

251.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000556628

190_238

54.666666666666664

227.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000556897

190_238

121.66666666666667

294.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000557201

190_238

134.66666666666666

307.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000320084

181_303

134.66666666666666

307.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000420743

181_303

134.66666666666666

307.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000430246

181_303

121.66666666666667

294.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000449098

181_303

121.66666666666667

294.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000553300

181_303

121.66666666666667

294.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000554455

181_303

134.66666666666666

307.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000554969

181_303

121.66666666666667

294.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000555883

181_303

121.66666666666667

251.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000556628

181_303

54.666666666666664

227.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000556897

181_303

121.66666666666667

294.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000557201

181_303

134.66666666666666

307.0

Compositional bias

Note=Asp/Glu-rich (acidic)

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000556628

16_87

54.666666666666664

227.0

Domain

RRM

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000320084

155_161

134.66666666666666

307.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000420743

155_161

134.66666666666666

307.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000430246

155_161

121.66666666666667

294.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000449098

155_161

121.66666666666667

294.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000553300

155_161

121.66666666666667

294.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000554455

155_161

134.66666666666666

307.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000554969

155_161

121.66666666666667

294.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000555883

155_161

121.66666666666667

251.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000556628

155_161

54.666666666666664

227.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000556897

155_161

121.66666666666667

294.0

Motif

Nuclear localization signal

Hgene

HNRNPC

chr14:21698478

chr8:31030511

ENST00000557201

155_161

134.66666666666666

307.0

Motif

Nuclear localization signal

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

507_510

1397.0

1433.0

Compositional bias

Note=Poly-Glu

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

1150_1229

1397.0

1433.0

Domain

HRDC

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

558_724

1397.0

1433.0

Domain

Helicase ATP-binding

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

60_228

1397.0

1433.0

Domain

Note=3'-5' exonuclease

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

749_899

1397.0

1433.0

Domain

Helicase C-terminal

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

668_671

1397.0

1433.0

Motif

Note=DEAH box

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

571_578

1397.0

1433.0

Nucleotide binding

ATP

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

424_477

1397.0

1433.0

Region

Note=2 X 27 AA tandem repeats of H-L-S-P-N-D-N-E-N-D-T-S-Y-V-I-E-S-D-E-D-L-E-M-E-M-L-K

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

424_450

1397.0

1433.0

Repeat

Tgene

WRN

chr14:21698478

chr8:31030511

ENST00000298139

451_477

1397.0

1433.0

Repeat

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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 >>>141_HNRNPC_21698478_WRN_31030511_ranked_0.pdb	HNRNPC	21698478	21698478	ENST00000298139	WRN	chr8	31030511	+	MASNVTNKTDPRSMNSRVFIGNLNTLVVKKSDVEAIFSKYGKIVGCSVHKGFAFVQYVNERNARAAVAGEDGRMIAGQVLDINLAAEPKV	158

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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.

HNRNPC_pLDDT.png

WRN_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
HNRNPC
WRN

- 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
Tgene	WRN	chr14:21698478	chr8:31030511	ENST00000298139		33	35	987_993	1397.0	1433.0	DNA
Tgene	WRN	chr14:21698478	chr8:31030511	ENST00000298139		33	35	2_277	1397.0	1433.0	WRNIP1

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Related Drugs to HNRNPC-WRN

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 HNRNPC-WRN

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