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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:CDH3-CHKA

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: CDH3-CHKA
	FusionPDB ID: 15072
	FusionGDB2.0 ID: 15072
		Hgene	Tgene
	Gene symbol	CDH3	CHKA
	Gene ID	1013	1119
	Gene name	cadherin 15	choline kinase alpha
	Synonyms	CDH14\|CDH3\|CDHM\|MCAD\|MRD3	CHK\|CK\|CKI\|EK
	Cytomap	16q24.3	11q13.2
	Type of gene	protein-coding	protein-coding
	Description	cadherin-15cadherin 15, type 1, M-cadherin (myotubule)cadherin-14cadherin-3muscle-cadherin	choline kinase alphaCHETK-alphaethanolamine kinase
	Modification date	20200313	20200313
	UniProtAcc	P22223	P35790
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000264012, ENST00000429102, ENST00000581171, ENST00000569117,	ENST00000356135, ENST00000533728, ENST00000265689,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	12 X 8 X 6=576	11 X 10 X 7=770
	# samples	15	13
	** MAII score	log2(15/576*10)=-1.94110631094643 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(13/770*10)=-2.56634682255381 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: CDH3 [Title/Abstract] AND CHKA [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	CDH3(68718727)-CHKA(67836404), # samples:4
Anticipated loss of major functional domain due to fusion event.	CDH3-CHKA 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. CDH3-CHKA 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. CDH3-CHKA 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. CDH3-CHKA 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
Tgene	CHKA	GO:0006646	phosphatidylethanolamine biosynthetic process	19915674
Tgene	CHKA	GO:0006656	phosphatidylcholine biosynthetic process	19915674

Fusion gene breakpoints across CDH3 (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 CHKA (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	BLCA	TCGA-DK-A6AV-01A	CDH3	chr16	68718727	-	CHKA	chr11	67836404	-
ChimerDB4	BLCA	TCGA-DK-A6AV-01A	CDH3	chr16	68718727	+	CHKA	chr11	67836404	-
ChimerDB4	BLCA	TCGA-DK-A6AV	CDH3	chr16	68718727	+	CHKA	chr11	67836404	-

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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)
ENST00000264012	CDH3	chr16	68718727	+	ENST00000265689	CHKA	chr11	67836404	-	3602	1968	346	2472	708
ENST00000429102	CDH3	chr16	68718727	+	ENST00000265689	CHKA	chr11	67836404	-	3445	1811	189	2315	708
ENST00000581171	CDH3	chr16	68718727	+	ENST00000265689	CHKA	chr11	67836404	-	3022	1388	54	1892	612

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
ENST00000264012	ENST00000265689	CDH3	chr16	68718727	+	CHKA	chr11	67836404	-	0.000862223	0.99913776
ENST00000429102	ENST00000265689	CDH3	chr16	68718727	+	CHKA	chr11	67836404	-	0.000902238	0.9990978
ENST00000581171	ENST00000265689	CDH3	chr16	68718727	+	CHKA	chr11	67836404	-	0.001012625	0.9989874

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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

>15072_15072_1_CDH3-CHKA_CDH3_chr16_68718727_ENST00000264012_CHKA_chr11_67836404_ENST00000265689_length(amino acids)=708AA_BP=540
MGPQPHPHRSHLRGGGTSWRWTNQHPPALTWPPPAGSRGLRCSKGQELSGTPARRRGSCFTPLSAAMGLPRGPLASLLLLQVCWLQCAAS
EPCRAVFREAEVTLEAGGAEQEPGQALGKVFMGCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI
SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKPLDREEIAKYELFGHAVSENGASVEDPMNISII
VTDQNDHKPKFTQDTFRGSVLEGVLPGTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDREKVPEY
TLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGHEVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPE
SNQGILTTRKGLDFEAKNQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPVCVYTAEDPDKENQKI
RSLLESTPSPVVFCHNDCQEGNILLLEGRENSEKQKLMLIDFEYSSYNYRGFDIGNHFCEWMYDYSYEKYPFFRANIRKYPTKKQQLHFI

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

>15072_15072_2_CDH3-CHKA_CDH3_chr16_68718727_ENST00000429102_CHKA_chr11_67836404_ENST00000265689_length(amino acids)=708AA_BP=540
MGPQPHPHRSHLRGGGTSWRWTNQHPPALTWPPPAGSRGLRCSKGQELSGTPARRRGSCFTPLSAAMGLPRGPLASLLLLQVCWLQCAAS
EPCRAVFREAEVTLEAGGAEQEPGQALGKVFMGCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI
SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKPLDREEIAKYELFGHAVSENGASVEDPMNISII
VTDQNDHKPKFTQDTFRGSVLEGVLPGTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDREKVPEY
TLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGHEVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPE
SNQGILTTRKGLDFEAKNQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPVCVYTAEDPDKENQKI
RSLLESTPSPVVFCHNDCQEGNILLLEGRENSEKQKLMLIDFEYSSYNYRGFDIGNHFCEWMYDYSYEKYPFFRANIRKYPTKKQQLHFI

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

>15072_15072_3_CDH3-CHKA_CDH3_chr16_68718727_ENST00000581171_CHKA_chr11_67836404_ENST00000265689_length(amino acids)=612AA_BP=444
MLHPSLCSHGAPSWTSRVSPPSPVFMGCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPISVPENG
KGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKPLDREEIAKYELFGHAVSENGASVEDPMNISIIVTDQND
HKPKFTQDTFRGSVLEGVLPGTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDREKVPEYTLTIQA
TDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGHEVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPESNQGIL
TTRKGLDFEAKNQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPVCVYTAEDPDKENQKIRSLLES
TPSPVVFCHNDCQEGNILLLEGRENSEKQKLMLIDFEYSSYNYRGFDIGNHFCEWMYDYSYEKYPFFRANIRKYPTKKQQLHFISSYLPA

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

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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/chr16:68718727/chr11:67836404)
- 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
CDH3 P22223	CHKA P35790
FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.	FUNCTION: Has a key role in phospholipid biosynthesis and may contribute to tumor cell growth. Catalyzes the first step in phosphatidylcholine biosynthesis. Contributes to phosphatidylethanolamine biosynthesis. Phosphorylates choline and ethanolamine. Has higher activity with choline. {ECO:0000269\|PubMed:19915674}.

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

CDH3

chr16:68718727

chr11:67836404

ENST00000264012

108_215

474.6666666666667

830.0

Domain

Cadherin 1

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000264012

216_328

474.6666666666667

830.0

Domain

Cadherin 2

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000264012

329_440

474.6666666666667

830.0

Domain

Cadherin 3

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000429102

108_215

474.6666666666667

785.0

Domain

Cadherin 1

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000429102

216_328

474.6666666666667

785.0

Domain

Cadherin 2

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000429102

329_440

474.6666666666667

785.0

Domain

Cadherin 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

CDH3

chr16:68718727

chr11:67836404

ENST00000264012

785_800

474.6666666666667

830.0

Compositional bias

Note=Ser-rich

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000429102

785_800

474.6666666666667

785.0

Compositional bias

Note=Ser-rich

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000264012

441_546

474.6666666666667

830.0

Domain

Cadherin 4

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000264012

547_650

474.6666666666667

830.0

Domain

Cadherin 5

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000429102

441_546

474.6666666666667

785.0

Domain

Cadherin 4

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000429102

547_650

474.6666666666667

785.0

Domain

Cadherin 5

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000264012

108_654

474.6666666666667

830.0

Topological domain

Extracellular

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000264012

678_829

474.6666666666667

830.0

Topological domain

Cytoplasmic

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000429102

108_654

474.6666666666667

785.0

Topological domain

Extracellular

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000429102

678_829

474.6666666666667

785.0

Topological domain

Cytoplasmic

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000264012

655_677

474.6666666666667

830.0

Transmembrane

Helical

Hgene

CDH3

chr16:68718727

chr11:67836404

ENST00000429102

655_677

474.6666666666667

785.0

Transmembrane

Helical

Tgene

CHKA

chr16:68718727

chr11:67836404

ENST00000265689

50_85

289.6666666666667

458.0

Compositional bias

Note=Pro-rich

Tgene

CHKA

chr16:68718727

chr11:67836404

ENST00000356135

50_85

271.6666666666667

440.0

Compositional bias

Note=Pro-rich

Tgene

CHKA

chr16:68718727

chr11:67836404

ENST00000265689

117_123

289.6666666666667

458.0

Nucleotide binding

Note=ATP

Tgene

CHKA

chr16:68718727

chr11:67836404

ENST00000265689

207_213

289.6666666666667

458.0

Nucleotide binding

Note=ATP

Tgene

CHKA

chr16:68718727

chr11:67836404

ENST00000356135

117_123

271.6666666666667

440.0

Nucleotide binding

Note=ATP

Tgene

CHKA

chr16:68718727

chr11:67836404

ENST00000356135

207_213

271.6666666666667

440.0

Nucleotide binding

Note=ATP

Tgene

CHKA

chr16:68718727

chr11:67836404

ENST00000265689

119_121

289.6666666666667

458.0

Region

Note=Substrate binding

Tgene

CHKA

chr16:68718727

chr11:67836404

ENST00000356135

119_121

271.6666666666667

440.0

Region

Note=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 >>>1447_CDH3_68718727_CHKA_67836404_ranked_0.pdb	CDH3	68718727	68718727	ENST00000265689	CHKA	chr11	67836404	-	MGPQPHPHRSHLRGGGTSWRWTNQHPPALTWPPPAGSRGLRCSKGQELSGTPARRRGSCFTPLSAAMGLPRGPLASLLLLQVCWLQCAAS EPCRAVFREAEVTLEAGGAEQEPGQALGKVFMGCPGQEPALFSTDNDDFTVRNGETVQERRSLKERNPLKIFPSKRILRRHKRDWVVAPI SVPENGKGPFPQRLNQLKSNKDRDTKIFYSITGPGADSPPEGVFAVEKETGWLLLNKPLDREEIAKYELFGHAVSENGASVEDPMNISII VTDQNDHKPKFTQDTFRGSVLEGVLPGTSVMQVTATDEDDAIYTYNGVVAYSIHSQEPKDPHDLMFTIHRSTGTISVISSGLDREKVPEY TLTIQATDMDGDGSTTTAVAVVEILDANDNAPMFDPQKYEAHVPENAVGHEVQRLTVTDLDAPNSPAWRATYLIMGGDDGDHFTITTHPE SNQGILTTRKGLDFEAKNQHTLYVEVTNEAPFVLKLPTSTATIVVHVEDVNEAPVFVPPSKVVEVQEGIPTGEPVCVYTAEDPDKENQKI RSLLESTPSPVVFCHNDCQEGNILLLEGRENSEKQKLMLIDFEYSSYNYRGFDIGNHFCEWMYDYSYEKYPFFRANIRKYPTKKQQLHFI	708

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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.

CDH3_pLDDT.png

CHKA_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
CDH3
CHKA

- 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 CDH3-CHKA

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 CDH3-CHKA

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