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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:CYTH1-MACROD1

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: CYTH1-MACROD1
	FusionPDB ID: 21142
	FusionGDB2.0 ID: 21142
		Hgene	Tgene
	Gene symbol	CYTH1	MACROD1
	Gene ID	9267	28992
	Gene name	cytohesin 1	mono-ADP ribosylhydrolase 1
	Synonyms	B2-1\|CYTOHESIN-1\|D17S811E\|PSCD1\|SEC7	LRP16
	Cytomap	17q25.3	11q13.1
	Type of gene	protein-coding	protein-coding
	Description	cytohesin-1PH, SEC7 and coiled-coil domain-containing protein 1SEC7 homolog B2-1cytoadhesin 1homolog of secretory protein SEC7pleckstrin homology, Sec7 and coiled-coil domains 1	ADP-ribose glycohydrolase MACROD1MACRO domain containing 1MACRO domain-containing protein 1O-acetyl-ADP-ribose deacetylase MACROD1[Protein ADP-ribosylaspartate] hydrolase MACROD1[Protein ADP-ribosylglutamate] hydrolase[Protein ADP-ribosylglutamate]
	Modification date	20200313	20200313
	UniProtAcc	Q15438	Q9BQ69
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000361101, ENST00000446868, ENST00000585509, ENST00000589297, ENST00000591455, ENST00000586175, ENST00000589296,	ENST00000538595, ENST00000255681,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	18 X 13 X 7=1638	7 X 7 X 6=294
	# samples	19	8
	** MAII score	log2(19/1638*10)=-3.10786403331006 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(8/294*10)=-1.877744249949 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: CYTH1 [Title/Abstract] AND MACROD1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	CYTH1(76694351)-MACROD1(63782753), # samples:3
Anticipated loss of major functional domain due to fusion event.	CYTH1-MACROD1 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. CYTH1-MACROD1 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. CYTH1-MACROD1 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. CYTH1-MACROD1 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. CYTH1-MACROD1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. CYTH1-MACROD1 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	CYTH1	GO:0030155	regulation of cell adhesion	12606567
Tgene	MACROD1	GO:0042278	purine nucleoside metabolic process	21257746
Tgene	MACROD1	GO:0051725	protein de-ADP-ribosylation	23474712

Fusion gene breakpoints across CYTH1 (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 MACROD1 (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	LGG	TCGA-HT-A619-01A	CYTH1	chr17	76690146	-	MACROD1	chr11	63875439	-
ChimerDB4	LGG	TCGA-HT-A619-01A	CYTH1	chr17	76694351	-	MACROD1	chr11	63782753	-
ChimerDB4	LGG	TCGA-HT-A619	CYTH1	chr17	76694351	-	MACROD1	chr11	63782753	-

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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)
ENST00000589297	CYTH1	chr17	76694351	-	ENST00000255681	MACROD1	chr11	63782753	-	1948	1327	495	1787	430
ENST00000591455	CYTH1	chr17	76694351	-	ENST00000255681	MACROD1	chr11	63782753	-	1481	860	49	1320	423
ENST00000446868	CYTH1	chr17	76694351	-	ENST00000255681	MACROD1	chr11	63782753	-	1503	882	71	1342	423

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
ENST00000589297	ENST00000255681	CYTH1	chr17	76694351	-	MACROD1	chr11	63782753	-	0.007928492	0.99207145
ENST00000591455	ENST00000255681	CYTH1	chr17	76694351	-	MACROD1	chr11	63782753	-	0.014239204	0.98576087
ENST00000446868	ENST00000255681	CYTH1	chr17	76694351	-	MACROD1	chr11	63782753	-	0.013572533	0.9864275

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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

>21142_21142_1_CYTH1-MACROD1_CYTH1_chr17_76694351_ENST00000446868_MACROD1_chr11_63782753_ENST00000255681_length(amino acids)=423AA_BP=270
MEEDDSYVPSDLTAEERQELENIRRRKQELLADIQRLKDEIAEVANEIENLGSTEERKNMQRNKQVAMGRKKFNMDPKKGIQFLIENDLL
KNTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLNLVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCQCNNGVF
QSTDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNRGINDGGDLPEELLRNLYESIKNEPFKIPEDDGNDLTHTFFNPDREGWLLKL
ANSSLLGGGGVDGCIHRAAGPLLTDECRTLQSCKTGKAKITGGYRLPAKYVIHTVGPIAYGEPSASQAAELRSCYLSSLDLLLEHRLRSV

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

>21142_21142_2_CYTH1-MACROD1_CYTH1_chr17_76694351_ENST00000589297_MACROD1_chr11_63782753_ENST00000255681_length(amino acids)=430AA_BP=277
MARTLGPQERGLTVVPSDLTAEERQELENIRRRKQELLADIQRLKDEIAEVANEIENLGSTEERKNMQRNKQVAMGRKKFNMDPKKGIQF
LIENDLLKNTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLNLVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYC
QCNNGVFQSTDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNRGINDGGDLPEELLRNLYESIKNEPFKIPEDDGNDLTHTFFNPDR
EGWLLKLANSSLLGGGGVDGCIHRAAGPLLTDECRTLQSCKTGKAKITGGYRLPAKYVIHTVGPIAYGEPSASQAAELRSCYLSSLDLLL

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

>21142_21142_3_CYTH1-MACROD1_CYTH1_chr17_76694351_ENST00000591455_MACROD1_chr11_63782753_ENST00000255681_length(amino acids)=423AA_BP=270
MEEDDSYVPSDLTAEERQELENIRRRKQELLADIQRLKDEIAEVANEIENLGSTEERKNMQRNKQVAMGRKKFNMDPKKGIQFLIENDLL
KNTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLNLVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCQCNNGVF
QSTDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNRGINDGGDLPEELLRNLYESIKNEPFKIPEDDGNDLTHTFFNPDREGWLLKL
ANSSLLGGGGVDGCIHRAAGPLLTDECRTLQSCKTGKAKITGGYRLPAKYVIHTVGPIAYGEPSASQAAELRSCYLSSLDLLLEHRLRSV

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

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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/chr17:76694351/chr11:63782753)
- 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
CYTH1 Q15438	MACROD1 Q9BQ69
FUNCTION: Promotes guanine-nucleotide exchange on ARF1, ARF5 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization, through regulation of ARF6 activity. {ECO:0000250\|UniProtKB:Q9QX11, ECO:0000269\|PubMed:10652308, ECO:0000269\|PubMed:29420262, ECO:0000269\|PubMed:9653114}.	FUNCTION: Removes ADP-ribose from asparatate and glutamate residues in proteins bearing a single ADP-ribose moiety (PubMed:23474714, PubMed:23474712). Inactive towards proteins bearing poly-ADP-ribose (PubMed:23474714, PubMed:23474712). Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins (PubMed:21257746). Plays a role in estrogen signaling (PubMed:17893710, PubMed:17914104, PubMed:19403568). Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen (PubMed:19022849). May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation (PubMed:17893710, PubMed:17914104). Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction (PubMed:17914104). Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells (PubMed:17893710). Enhances ESR1-mediated transcription activity (PubMed:17914104). {ECO:0000269\|PubMed:17893710, ECO:0000269\|PubMed:17914104, ECO:0000269\|PubMed:19022849, ECO:0000269\|PubMed:19403568, ECO:0000269\|PubMed:21257746, ECO:0000269\|PubMed:23474712, ECO:0000269\|PubMed:23474714}.

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

CYTH1

chr17:76694351

chr11:63782753

ENST00000361101

10_67

270.6666666666667

399.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000446868

10_67

270.3333333333333

399.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000591455

10_67

270.3333333333333

398.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000361101

73_202

270.6666666666667

399.0

Domain

SEC7

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000446868

73_202

270.3333333333333

399.0

Domain

SEC7

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000591455

73_202

270.3333333333333

398.0

Domain

SEC7

Tgene

MACROD1

chr17:76694351

chr11:63782753

ENST00000255681

172_174

172.33333333333334

225.33333333333334

Region

Substrate binding

Tgene

MACROD1

chr17:76694351

chr11:63782753

ENST00000255681

179_184

172.33333333333334

225.33333333333334

Region

Substrate binding

Tgene

MACROD1

chr17:76694351

chr11:63782753

ENST00000255681

267_273

172.33333333333334

225.33333333333334

Region

Substrate binding

- 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

CYTH1

chr17:76694351

chr11:63782753

ENST00000361101

260_377

270.6666666666667

399.0

Domain

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000446868

260_377

270.3333333333333

399.0

Domain

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000591455

260_377

270.3333333333333

398.0

Domain

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000361101

269_277

270.6666666666667

399.0

Region

Phosphatidylinositol 3%2C4%2C5-trisphosphate binding

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000361101

388_396

270.6666666666667

399.0

Region

C-terminal autoinhibitory region

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000446868

269_277

270.3333333333333

399.0

Region

Phosphatidylinositol 3%2C4%2C5-trisphosphate binding

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000446868

388_396

270.3333333333333

399.0

Region

C-terminal autoinhibitory region

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000591455

269_277

270.3333333333333

398.0

Region

Phosphatidylinositol 3%2C4%2C5-trisphosphate binding

Hgene

CYTH1

chr17:76694351

chr11:63782753

ENST00000591455

388_396

270.3333333333333

398.0

Region

C-terminal autoinhibitory region

Tgene

MACROD1

chr17:76694351

chr11:63782753

ENST00000255681

141_322

172.33333333333334

225.33333333333334

Domain

Macro

Tgene

MACROD1

chr17:76694351

chr11:63782753

ENST00000255681

159_161

172.33333333333334

225.33333333333334

Region

Substrate binding

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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 >>>900_CYTH1_76694351_MACROD1_63782753_900_CYTH1_76694351_MACROD1_63782753_ranked_0.pdb	CYTH1	76694351	76694351	ENST00000255681	MACROD1	chr11	63782753	-	MARTLGPQERGLTVVPSDLTAEERQELENIRRRKQELLADIQRLKDEIAEVANEIENLGSTEERKNMQRNKQVAMGRKKFNMDPKKGIQF LIENDLLKNTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLNLVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYC QCNNGVFQSTDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNRGINDGGDLPEELLRNLYESIKNEPFKIPEDDGNDLTHTFFNPDR EGWLLKLANSSLLGGGGVDGCIHRAAGPLLTDECRTLQSCKTGKAKITGGYRLPAKYVIHTVGPIAYGEPSASQAAELRSCYLSSLDLLL	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.

CYTH1_pLDDT.png

MACROD1_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
CYTH1
MACROD1

- 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 CYTH1-MACROD1

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 CYTH1-MACROD1

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