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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:CRTC3-MESP2

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: CRTC3-MESP2
	FusionPDB ID: 19574
	FusionGDB2.0 ID: 19574
		Hgene	Tgene
	Gene symbol	CRTC3	MESP2
	Gene ID	64784	145873
	Gene name	CREB regulated transcription coactivator 3	mesoderm posterior bHLH transcription factor 2
	Synonyms	TORC-3\|TORC3	SCDO2\|bHLHc6
	Cytomap	15q26.1	15q26.1
	Type of gene	protein-coding	protein-coding
	Description	CREB-regulated transcription coactivator 3transducer of regulated CREB protein 3transducer of regulated cAMP response element-binding protein (CREB) 3	mesoderm posterior protein 2class C basic helix-loop-helix protein 6mesoderm posterior 2 homologmesoderm posterior basic helix-loop-helix transcription factor 2
	Modification date	20200313	20200313
	UniProtAcc	Q6UUV7	Q0VG99
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000268184, ENST00000420329, ENST00000558619, ENST00000560098,	ENST00000341735, ENST00000558723, ENST00000560219,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	7 X 6 X 7=294	5 X 4 X 4=80
	# samples	9	5
	** MAII score	log2(9/294*10)=-1.70781924850669 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(5/80*10)=-0.678071905112638 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: CRTC3 [Title/Abstract] AND MESP2 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	CRTC3(91182047)-MESP2(90321296), # samples:3
Anticipated loss of major functional domain due to fusion event.	CRTC3-MESP2 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. CRTC3-MESP2 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. CRTC3-MESP2 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. CRTC3-MESP2 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

Fusion gene breakpoints across CRTC3 (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 MESP2 (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	UCS	TCGA-NA-A4R1-01A	CRTC3	chr15	91182047	-	MESP2	chr15	90321296	+
ChimerDB4	UCS	TCGA-NA-A4R1-01A	CRTC3	chr15	91182047	+	MESP2	chr15	90321296	+
ChimerDB4	UCS	TCGA-NA-A4R1	CRTC3	chr15	91182047	+	MESP2	chr15	90321296	+

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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)

ENST00000420329

CRTC3

chr15

91182047

ENST00000560219

MESP2

chr15

90321296

2382

1695

147

1964

605

ENST00000268184

CRTC3

chr15

91182047

ENST00000560219

MESP2

chr15

90321296

2239

1552

1821

605

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
ENST00000420329	ENST00000560219	CRTC3	chr15	91182047	+	MESP2	chr15	90321296	+	0.061630234	0.93836975
ENST00000268184	ENST00000560219	CRTC3	chr15	91182047	+	MESP2	chr15	90321296	+	0.06718763	0.93281233

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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

>19574_19574_1_CRTC3-MESP2_CRTC3_chr15_91182047_ENST00000268184_MESP2_chr15_90321296_ENST00000560219_length(amino acids)=605AA_BP=509
MAASPGSGSANPRKFSEKIALHTQRQAEETRAFEQLMTDLTLSRVQFQKLQQLRLTQYHGGSLPNVSQLRSSASEFQPSFHQADNVRGTR
HHGLVERPSRNRFHPLHRRSGDKPGRQFDGSAFGANYSSQPLDESWPRQQPPWKDEKHPGFRLTSALNRTNSDSALHTSALSTKPQDPYG
GGGQSAWPAPYMGFCDGENNGHGEVASFPGPLKEENLLNVPKPLPKQLWETKEIQSLSGRPRSCDVGGGNAFPHNGQNLGLSPFLGTLNT
GGSLPDLTNLHYSTPLPASLDTTDHHFGSMSVGNSVNNIPAAMTHLGIRSSSGLQSSRSNPSIQATLNKTVLSSSLNNHPQTSVPNASAL
HPSLRLFSLSNPSLSTTNLSGPSRRRQPPVSPLTLSPGPEAHQGFSRQLSSTSPLAPYPTSQMVSSDRSQLSFLPTEAQAQVSPPPPYPA
PQELTQPLLQQPRAPEAPAQQPQAASSLPQSDFQLLPAQGSSLTNFFPDVGFDQQSMRPGPAFPQQGLSVSPEPCLSLGAPSLLPHPSCQ

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

>19574_19574_2_CRTC3-MESP2_CRTC3_chr15_91182047_ENST00000420329_MESP2_chr15_90321296_ENST00000560219_length(amino acids)=605AA_BP=509
MAASPGSGSANPRKFSEKIALHTQRQAEETRAFEQLMTDLTLSRVQFQKLQQLRLTQYHGGSLPNVSQLRSSASEFQPSFHQADNVRGTR
HHGLVERPSRNRFHPLHRRSGDKPGRQFDGSAFGANYSSQPLDESWPRQQPPWKDEKHPGFRLTSALNRTNSDSALHTSALSTKPQDPYG
GGGQSAWPAPYMGFCDGENNGHGEVASFPGPLKEENLLNVPKPLPKQLWETKEIQSLSGRPRSCDVGGGNAFPHNGQNLGLSPFLGTLNT
GGSLPDLTNLHYSTPLPASLDTTDHHFGSMSVGNSVNNIPAAMTHLGIRSSSGLQSSRSNPSIQATLNKTVLSSSLNNHPQTSVPNASAL
HPSLRLFSLSNPSLSTTNLSGPSRRRQPPVSPLTLSPGPEAHQGFSRQLSSTSPLAPYPTSQMVSSDRSQLSFLPTEAQAQVSPPPPYPA
PQELTQPLLQQPRAPEAPAQQPQAASSLPQSDFQLLPAQGSSLTNFFPDVGFDQQSMRPGPAFPQQGLSVSPEPCLSLGAPSLLPHPSCQ

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

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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/chr15:91182047/chr15:90321296)
- 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
CRTC3 Q6UUV7	MESP2 Q0VG99
FUNCTION: Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269\|PubMed:14506290, ECO:0000269\|PubMed:15454081, ECO:0000269\|PubMed:15466468, ECO:0000269\|PubMed:16817901, ECO:0000269\|PubMed:16980408, ECO:0000269\|PubMed:17210223, ECO:0000269\|PubMed:17644518}.	FUNCTION: Transcription factor with important role in somitogenesis. Defines the rostrocaudal patterning of the somite by participating in distinct Notch pathways. Regulates also the FGF signaling pathway. Specifies the rostral half of the somites. Generates rostro-caudal polarity of somites by down-regulating in the presumptive rostral domain DLL1, a Notch ligand. Participates in the segment border formation by activating in the anterior presomitic mesoderm LFNG, a negative regulator of DLL1-Notch signaling. Acts as a strong suppressor of Notch activity. Together with MESP1 is involved in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm.

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

CRTC3

chr15:91182047

chr15:90321296

ENST00000268184

180_183

516.0

620.0

Compositional bias

Note=Poly-Gly

Hgene

CRTC3

chr15:91182047

chr15:90321296

ENST00000268184

444_451

516.0

620.0

Compositional bias

Note=Poly-Pro

Hgene

CRTC3

chr15:91182047

chr15:90321296

ENST00000420329

180_183

516.0

619.0

Compositional bias

Note=Poly-Gly

Hgene

CRTC3

chr15:91182047

chr15:90321296

ENST00000420329

444_451

516.0

619.0

Compositional bias

Note=Poly-Pro

- 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

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

81_135

308.0

398.0

Domain

bHLH

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

179_204

308.0

398.0

Region

Note=13 X 2 AA tandem repeats of G-Q

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

179_180

308.0

398.0

Repeat

Note=1

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

181_182

308.0

398.0

Repeat

Note=2

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

183_184

308.0

398.0

Repeat

Note=3

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

185_186

308.0

398.0

Repeat

Note=4

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

187_188

308.0

398.0

Repeat

Note=5

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

189_190

308.0

398.0

Repeat

Note=6

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

191_192

308.0

398.0

Repeat

Note=7

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

193_194

308.0

398.0

Repeat

Note=8

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

195_196

308.0

398.0

Repeat

Note=9

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

197_198

308.0

398.0

Repeat

Note=10

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

199_200

308.0

398.0

Repeat

Note=11

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

201_202

308.0

398.0

Repeat

Note=12

Tgene

MESP2

chr15:91182047

chr15:90321296

ENST00000341735

203_204

308.0

398.0

Repeat

Note=13

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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 >>>1280_CRTC3_91182047_MESP2_90321296_1280_CRTC3_91182047_MESP2_90321296_ranked_0.pdb	CRTC3	91182047	91182047	ENST00000560219	MESP2	chr15	90321296	+	MAASPGSGSANPRKFSEKIALHTQRQAEETRAFEQLMTDLTLSRVQFQKLQQLRLTQYHGGSLPNVSQLRSSASEFQPSFHQADNVRGTR HHGLVERPSRNRFHPLHRRSGDKPGRQFDGSAFGANYSSQPLDESWPRQQPPWKDEKHPGFRLTSALNRTNSDSALHTSALSTKPQDPYG GGGQSAWPAPYMGFCDGENNGHGEVASFPGPLKEENLLNVPKPLPKQLWETKEIQSLSGRPRSCDVGGGNAFPHNGQNLGLSPFLGTLNT GGSLPDLTNLHYSTPLPASLDTTDHHFGSMSVGNSVNNIPAAMTHLGIRSSSGLQSSRSNPSIQATLNKTVLSSSLNNHPQTSVPNASAL HPSLRLFSLSNPSLSTTNLSGPSRRRQPPVSPLTLSPGPEAHQGFSRQLSSTSPLAPYPTSQMVSSDRSQLSFLPTEAQAQVSPPPPYPA PQELTQPLLQQPRAPEAPAQQPQAASSLPQSDFQLLPAQGSSLTNFFPDVGFDQQSMRPGPAFPQQGLSVSPEPCLSLGAPSLLPHPSCQ	605

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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.

CRTC3_pLDDT.png

MESP2_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
CRTC3	YWHAG, YWHAB, SCYL1, NEDD1, MAGEA10, EWSR1, CENPJ, XPO1, CLTC, HCCS, HSPA5, POLD1, MAPK8, LRP8, GTSE1, PCDHB15, CFAP97, Chmp4b, Sec24c, MCM2, DCAF7, KCTD3, KIF13B, CGN, ZBTB21, KSR1, CBY1, Stat3, MDM2, TRIM25, EGLN3, KLHL12, NEDD4L, SIK2, HDAC2, nsp12, CA13, PLEKHA4, KIF14, nsp12ab, INS, DDX58, KIAA1549, LRRC73, YWHAH, S100A2, YWHAQ, S100P,

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
CRTC3
MESP2

- 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 CRTC3-MESP2

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 CRTC3-MESP2

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