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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:DCK-GRSF1

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: DCK-GRSF1
	FusionPDB ID: 21609
	FusionGDB2.0 ID: 21609
		Hgene	Tgene
	Gene symbol	DCK	GRSF1
	Gene ID	1633	2926
	Gene name	deoxycytidine kinase	G-rich RNA sequence binding factor 1
	Synonyms	-	-
	Cytomap	4q13.3	4q13.3
	Type of gene	protein-coding	protein-coding
	Description	deoxycytidine kinasedeoxynucleoside kinase	G-rich sequence factor 1
	Modification date	20200313	20200313
	UniProtAcc	P27707	Q12849
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000286648, ENST00000504730, ENST00000504952,	ENST00000439371, ENST00000502323, ENST00000508091, ENST00000545193, ENST00000254799,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	1 X 1 X 1=1	11 X 10 X 4=440
	# samples	1	11
	** MAII score	log2(1/1*10)=3.32192809488736	log2(11/440*10)=-2 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: DCK [Title/Abstract] AND GRSF1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	DCK(71863899)-GRSF1(71702031), # samples:3
Anticipated loss of major functional domain due to fusion event.	DCK-GRSF1 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. DCK-GRSF1 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. DCK-GRSF1 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. DCK-GRSF1 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	DCK	GO:0006220	pyrimidine nucleotide metabolic process	12808445
Tgene	GRSF1	GO:0000962	positive regulation of mitochondrial RNA catabolic process	29967381

Fusion gene breakpoints across DCK (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 GRSF1 (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	BRCA	TCGA-BH-A1F2-01A	DCK	chr4	71863899	-	GRSF1	chr4	71702031	-
ChimerDB4	BRCA	TCGA-BH-A1F2-01A	DCK	chr4	71863899	+	GRSF1	chr4	71702031	-
ChimerDB4	BRCA	TCGA-BH-A1F2	DCK	chr4	71863899	+	GRSF1	chr4	71702031	-

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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)
ENST00000286648	DCK	chr4	71863899	+	ENST00000254799	GRSF1	chr4	71702031	-	6795	604	397	1689	430
ENST00000504952	DCK	chr4	71863899	+	ENST00000254799	GRSF1	chr4	71702031	-	6596	405	198	1490	430
ENST00000504730	DCK	chr4	71863899	+	ENST00000254799	GRSF1	chr4	71702031	-	6596	405	198	1490	430

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
ENST00000286648	ENST00000254799	DCK	chr4	71863899	+	GRSF1	chr4	71702031	-	0.000200501	0.99979955
ENST00000504952	ENST00000254799	DCK	chr4	71863899	+	GRSF1	chr4	71702031	-	0.000196002	0.99980396
ENST00000504730	ENST00000254799	DCK	chr4	71863899	+	GRSF1	chr4	71702031	-	0.000196002	0.99980396

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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

>21609_21609_1_DCK-GRSF1_DCK_chr4_71863899_ENST00000286648_GRSF1_chr4_71702031_ENST00000254799_length(amino acids)=430AA_BP=69
MATPPKRSCPSFSASSEGTRIKKISIEGNIAAGKSTFVNILKQLCEDWEVVPEPVARWCNVQSTQDEFEESKTTYLEDLPPPPEYELAPS
KLEEEVDDVFLIRAQGLPWSCTMEDVLNFFSDCRIRNGENGIHFLLNRDGKRRGDALIEMESEQDVQKALEKHRMYMGQRYVEVYEINNE
DVDALMKSLQVKSSPVVNDGVVRLRGLPYSCNEKDIVDFFAGLNIVDITFVMDYRGRRKTGEAYVQFEEPEMANQALLKHREEIGNRYIE
IFPSRRNEVRTHVGSYKGKKIASFPTAKYITEPEMVFEEHEVNEDIQPMTAFESEKEIELPKEVPEKLPEAADFGTTSSLHFVHMRGLPF

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

>21609_21609_2_DCK-GRSF1_DCK_chr4_71863899_ENST00000504730_GRSF1_chr4_71702031_ENST00000254799_length(amino acids)=430AA_BP=69
MATPPKRSCPSFSASSEGTRIKKISIEGNIAAGKSTFVNILKQLCEDWEVVPEPVARWCNVQSTQDEFEESKTTYLEDLPPPPEYELAPS
KLEEEVDDVFLIRAQGLPWSCTMEDVLNFFSDCRIRNGENGIHFLLNRDGKRRGDALIEMESEQDVQKALEKHRMYMGQRYVEVYEINNE
DVDALMKSLQVKSSPVVNDGVVRLRGLPYSCNEKDIVDFFAGLNIVDITFVMDYRGRRKTGEAYVQFEEPEMANQALLKHREEIGNRYIE
IFPSRRNEVRTHVGSYKGKKIASFPTAKYITEPEMVFEEHEVNEDIQPMTAFESEKEIELPKEVPEKLPEAADFGTTSSLHFVHMRGLPF

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

>21609_21609_3_DCK-GRSF1_DCK_chr4_71863899_ENST00000504952_GRSF1_chr4_71702031_ENST00000254799_length(amino acids)=430AA_BP=69
MATPPKRSCPSFSASSEGTRIKKISIEGNIAAGKSTFVNILKQLCEDWEVVPEPVARWCNVQSTQDEFEESKTTYLEDLPPPPEYELAPS
KLEEEVDDVFLIRAQGLPWSCTMEDVLNFFSDCRIRNGENGIHFLLNRDGKRRGDALIEMESEQDVQKALEKHRMYMGQRYVEVYEINNE
DVDALMKSLQVKSSPVVNDGVVRLRGLPYSCNEKDIVDFFAGLNIVDITFVMDYRGRRKTGEAYVQFEEPEMANQALLKHREEIGNRYIE
IFPSRRNEVRTHVGSYKGKKIASFPTAKYITEPEMVFEEHEVNEDIQPMTAFESEKEIELPKEVPEKLPEAADFGTTSSLHFVHMRGLPF

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

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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/chr4:71863899/chr4:71702031)
- 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
DCK P27707	GRSF1 Q12849
FUNCTION: Phosphorylates the deoxyribonucleosides deoxycytidine, deoxyguanosine and deoxyadenosine (PubMed:1996353, PubMed:12808445, PubMed:18377927, PubMed:19159229, PubMed:20614893). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents (PubMed:12808445). {ECO:0000269\|PubMed:12808445, ECO:0000269\|PubMed:18377927, ECO:0000269\|PubMed:19159229, ECO:0000269\|PubMed:1996353, ECO:0000269\|PubMed:20614893}.	FUNCTION: Regulator of post-transcriptional mitochondrial gene expression, required for assembly of the mitochondrial ribosome and for recruitment of mRNA and lncRNA. Binds RNAs containing the 14 base G-rich element. Preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long non-coding RNAs for MT-CYB and MT-ND5, each of which contains multiple consensus binding sequences (PubMed:23473033, PubMed:23473034, PubMed:29967381). Involved in the degradosome-mediated decay of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like molecules (PubMed:29967381). Acts by unwinding G-quadruplex RNA structures in MT-ncRNA, thus facilitating their degradation by the degradosome (PubMed:29967381). G-quadruplexes (G4) are non-canonical 4 stranded structures formed by transcripts from the light strand of mtDNA (PubMed:29967381). {ECO:0000269\|PubMed:23473033, ECO:0000269\|PubMed:23473034, ECO:0000269\|PubMed:29967381}.

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

DCK

chr4:71863899

chr4:71702031

ENST00000286648

28_36

69.0

261.0

Nucleotide binding

Note=ATP

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000439371

55_111

1891.3333333333333

Compositional bias

Note=Ala-rich

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000502323

55_111

430.6666666666667

Compositional bias

Note=Ala-rich

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000254799

122_246

119.0

1988.6666666666667

Domain

RRM 1

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000254799

250_326

119.0

1988.6666666666667

Domain

RRM 2

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000254799

401_480

119.0

1988.6666666666667

Domain

RRM 3

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000439371

122_246

1891.3333333333333

Domain

RRM 1

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000439371

250_326

1891.3333333333333

Domain

RRM 2

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000439371

401_480

1891.3333333333333

Domain

RRM 3

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000502323

122_246

430.6666666666667

Domain

RRM 1

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000502323

250_326

430.6666666666667

Domain

RRM 2

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000502323

401_480

430.6666666666667

Domain

RRM 3

- 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

DCK

chr4:71863899

chr4:71702031

ENST00000286648

188_192

69.0

261.0

Nucleotide binding

Note=ATP

Hgene

DCK

chr4:71863899

chr4:71702031

ENST00000286648

240_242

69.0

261.0

Nucleotide binding

Note=ATP

Tgene

GRSF1

chr4:71863899

chr4:71702031

ENST00000254799

55_111

119.0

1988.6666666666667

Compositional bias

Note=Ala-rich

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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 >>>901_DCK_71863899_GRSF1_71702031_901_DCK_71863899_GRSF1_71702031_ranked_0.pdb	DCK	71863899	71863899	ENST00000254799	GRSF1	chr4	71702031	-	MATPPKRSCPSFSASSEGTRIKKISIEGNIAAGKSTFVNILKQLCEDWEVVPEPVARWCNVQSTQDEFEESKTTYLEDLPPPPEYELAPS KLEEEVDDVFLIRAQGLPWSCTMEDVLNFFSDCRIRNGENGIHFLLNRDGKRRGDALIEMESEQDVQKALEKHRMYMGQRYVEVYEINNE DVDALMKSLQVKSSPVVNDGVVRLRGLPYSCNEKDIVDFFAGLNIVDITFVMDYRGRRKTGEAYVQFEEPEMANQALLKHREEIGNRYIE IFPSRRNEVRTHVGSYKGKKIASFPTAKYITEPEMVFEEHEVNEDIQPMTAFESEKEIELPKEVPEKLPEAADFGTTSSLHFVHMRGLPF	430

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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.

DCK_pLDDT.png

GRSF1_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
DCK
GRSF1

- 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 DCK-GRSF1

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 DCK-GRSF1

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