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Fusion Protein:CPT1A-ADAM2

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: CPT1A-ADAM2
	FusionPDB ID: 19209
	FusionGDB2.0 ID: 19209
		Hgene	Tgene
	Gene symbol	CPT1A	ADAM2
	Gene ID	1374	2515
	Gene name	carnitine palmitoyltransferase 1A	ADAM metallopeptidase domain 2
	Synonyms	CPT1\|CPT1-L\|L-CPT1	CRYN1\|CRYN2\|CT15\|FTNB\|PH-30b\|PH30\|PH30-beta
	Cytomap	11q13.3	8p11.22
	Type of gene	protein-coding	protein-coding
	Description	carnitine O-palmitoyltransferase 1, liver isoformCPT ICPTI-Lcarnitine O-palmitoyltransferase I, liver isoformcarnitine palmitoyltransferase 1A (liver)carnitine palmitoyltransferase I, liver	disintegrin and metalloproteinase domain-containing protein 2cancer/testis antigen 15fertilin subunit beta
	Modification date	20200315	20200313
	UniProtAcc	P50416 Main function of 5'-partner protein: FUNCTION: Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion (PubMed:9691089, PubMed:11350182, PubMed:14517221). Plays an important role in hepatic triglyceride metabolism (By similarity). {ECO:0000250\|UniProtKB:P32198, ECO:0000269\|PubMed:11350182, ECO:0000269\|PubMed:14517221, ECO:0000269\|PubMed:9691089}.	Q9UKF5 Main function of 5'-partner protein: FUNCTION: May be involved in spermatogenesis and fertilization. Seems to be a non catalytic metalloprotease-like protein.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000265641, ENST00000376618, ENST00000539743, ENST00000540367, ENST00000537756, ENST00000538994,	ENST00000523181, ENST00000265708, ENST00000347580, ENST00000379853, ENST00000521880,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	25 X 23 X 12=6900	7 X 8 X 4=224
	# samples	32	10
	** MAII score	log2(32/6900*10)=-4.43045255166553 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(10/224*10)=-1.16349873228288 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: CPT1A [Title/Abstract] AND ADAM2 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: CPT1A [Title/Abstract] AND ADAM2 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	CPT1A(68540733)-ADAM2(39607263), # samples:3
Anticipated loss of major functional domain due to fusion event.	CPT1A-ADAM2 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. CPT1A-ADAM2 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. CPT1A-ADAM2 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. CPT1A-ADAM2 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. CPT1A-ADAM2 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. CPT1A-ADAM2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. CPT1A-ADAM2 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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	CPT1A	GO:0001676	long-chain fatty acid metabolic process	11350182
Hgene	CPT1A	GO:0009437	carnitine metabolic process	11350182

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr11:68540733/chr8:39607263)
- 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.

Retention analysis results 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, are available here.

Fusion gene breakpoints across CPT1A (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 ADAM2 (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 Amino Acid Sequences

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)
ENST00000540367	CPT1A	chr11	68540733	-	ENST00000347580	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000540367	CPT1A	chr11	68540733	-	ENST00000379853	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000540367	CPT1A	chr11	68540733	-	ENST00000265708	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000540367	CPT1A	chr11	68540733	-	ENST00000521880	ADAM2	chr8	39607263	-	2244	1769	23	2179	718
ENST00000539743	CPT1A	chr11	68540733	-	ENST00000347580	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000539743	CPT1A	chr11	68540733	-	ENST00000379853	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000539743	CPT1A	chr11	68540733	-	ENST00000265708	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000539743	CPT1A	chr11	68540733	-	ENST00000521880	ADAM2	chr8	39607263	-	2244	1769	23	2179	718
ENST00000540367	CPT1A	chr11	68540732	-	ENST00000347580	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000540367	CPT1A	chr11	68540732	-	ENST00000379853	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000540367	CPT1A	chr11	68540732	-	ENST00000265708	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000540367	CPT1A	chr11	68540732	-	ENST00000521880	ADAM2	chr8	39607263	-	2244	1769	23	2179	718
ENST00000539743	CPT1A	chr11	68540732	-	ENST00000347580	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000539743	CPT1A	chr11	68540732	-	ENST00000379853	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000539743	CPT1A	chr11	68540732	-	ENST00000265708	ADAM2	chr8	39607263	-	2540	1769	23	2179	718
ENST00000539743	CPT1A	chr11	68540732	-	ENST00000521880	ADAM2	chr8	39607263	-	2244	1769	23	2179	718

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
ENST00000540367	ENST00000347580	CPT1A	chr11	68540733	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000540367	ENST00000379853	CPT1A	chr11	68540733	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000540367	ENST00000265708	CPT1A	chr11	68540733	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000540367	ENST00000521880	CPT1A	chr11	68540733	-	ADAM2	chr8	39607263	-	0.002077068	0.99792296
ENST00000539743	ENST00000347580	CPT1A	chr11	68540733	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000539743	ENST00000379853	CPT1A	chr11	68540733	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000539743	ENST00000265708	CPT1A	chr11	68540733	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000539743	ENST00000521880	CPT1A	chr11	68540733	-	ADAM2	chr8	39607263	-	0.002077068	0.99792296
ENST00000540367	ENST00000347580	CPT1A	chr11	68540732	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000540367	ENST00000379853	CPT1A	chr11	68540732	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000540367	ENST00000265708	CPT1A	chr11	68540732	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000540367	ENST00000521880	CPT1A	chr11	68540732	-	ADAM2	chr8	39607263	-	0.002077068	0.99792296
ENST00000539743	ENST00000347580	CPT1A	chr11	68540732	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000539743	ENST00000379853	CPT1A	chr11	68540732	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000539743	ENST00000265708	CPT1A	chr11	68540732	-	ADAM2	chr8	39607263	-	0.000787307	0.9992126
ENST00000539743	ENST00000521880	CPT1A	chr11	68540732	-	ADAM2	chr8	39607263	-	0.002077068	0.99792296

Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for CPT1A-ADAM2

+/-13 AA sequence from the breakpoints of the fusion protein sequences.

Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Length(fusion protein)	BP in fusion protein	Peptide
CPT1A	chr11	68540732	ADAM2	chr8	39607263	1769	582	AFVQLALQLAHYKVCRNQRCVSSSYL
CPT1A	chr11	68540733	ADAM2	chr8	39607263	1769	582	AFVQLALQLAHYKVCRNQRCVSSSYL

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Potential FusionNeoAntigen Information of CPT1A-ADAM2 in HLA I

Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

CPT1A-ADAM2_68540732_39607263.msa

Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)

Fusion gene	Hchr	Hbp	Tgene	Tchr	Tbp	HLA I	FusionNeoAntigen peptide	Binding score	Immunogenic score	Neoantigen start (at BP 13)	Neoantigen end (at BP 13)
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-B52:01	LQLAHYKV	0.7849	0.9706	6	14
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-A02:27	ALQLAHYKV	0.9675	0.7674	5	14
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-A02:13	ALQLAHYKV	0.9666	0.8422	5	14
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-A02:11	ALQLAHYKV	0.957	0.7682	5	14
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-A02:16	ALQLAHYKV	0.9338	0.7191	5	14
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-A02:04	ALQLAHYKV	0.9172	0.839	5	14
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-A02:17	ALQLAHYKV	0.8795	0.6934	5	14
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-A31:02	QLAHYKVCR	0.8677	0.5224	7	16
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-A02:19	ALQLAHYKV	0.8491	0.7232	5	14
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-A02:35	ALQLAHYKV	0.8247	0.7734	5	14
CPT1A-ADAM2	chr11	68540732	chr8	39607263	1769	HLA-B13:02	ALQLAHYKV	0.0274	0.9292	5	14

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Potential FusionNeoAntigen Information of CPT1A-ADAM2 in HLA II

Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).

Fusion gene

Hchr

Hbp

Tgene

Tchr

Tbp

HLA II

FusionNeoAntigen peptide

Neoantigen start (at BP 13)

Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of CPT1A-ADAM2

3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

File name	BPseq	Hgene	Tgene	Hchr	Hbp	Tchr	Tbp	AAlen
5464	LQLAHYKVCRNQRC	CPT1A	ADAM2	chr11	68540732	chr8	39607263	1769

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CPT1A-ADAM2

Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.

HLA allele	PDB ID	File name	BPseq	Docking score	Glide score
HLA-B14:02	3BVN	5464	LQLAHYKVCRNQRC	-6.73939	-6.85279
HLA-B14:02	3BVN	5464	LQLAHYKVCRNQRC	-5.8572	-6.8925
HLA-B52:01	3W39	5464	LQLAHYKVCRNQRC	-6.06811	-6.18151
HLA-B52:01	3W39	5464	LQLAHYKVCRNQRC	-4.01521	-5.05051
HLA-A24:02	5HGA	5464	LQLAHYKVCRNQRC	-6.11611	-7.15141
HLA-A24:02	5HGA	5464	LQLAHYKVCRNQRC	-5.72969	-5.84309
HLA-B27:05	6PYJ	5464	LQLAHYKVCRNQRC	-6.42433	-7.45963
HLA-B44:05	3DX8	5464	LQLAHYKVCRNQRC	-5.79012	-5.90352
HLA-B44:05	3DX8	5464	LQLAHYKVCRNQRC	-3.82099	-4.85629

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Vaccine Design for the FusionNeoAntigens of CPT1A-ADAM2

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.

Fusion gene	Hchr	Hbp	Tchr	Tbp	Start in +/-13AA	End in +/-13AA	FusionNeoAntigen peptide sequence	FusionNeoAntigen RNA sequence
CPT1A-ADAM2	chr11	68540732	chr8	39607263	5	14	ALQLAHYKV	GCCCTCCAGCTGGCGCACTACAAGGTT
CPT1A-ADAM2	chr11	68540732	chr8	39607263	6	14	LQLAHYKV	CTCCAGCTGGCGCACTACAAGGTT
CPT1A-ADAM2	chr11	68540732	chr8	39607263	7	16	QLAHYKVCR	CAGCTGGCGCACTACAAGGTTTGCAGG

mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.

Fusion gene

Hchr

Hbp

Tchr

Tbp

Start in +/-13AA

End in +/-13AA

FusionNeoAntigen peptide

FusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of CPT1A-ADAM2

These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.

Cancer type	Fusion gene	Hchr	Hbp	Henst	Tchr	Tbp	Tenst	Sample
BRCA	CPT1A-ADAM2	chr11	68540732	ENST00000539743	chr8	39607263	ENST00000265708	TCGA-E2-A15R

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Potential target of CAR-T therapy development for CPT1A-ADAM2

Predicted 3D structure. We used RoseTTAFold.

121_CPT1A-ADAM2_t000_.e2e.pdb

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features

* Minus value of BPloci means that the break point is located before the CDS.

- In-frame and retained 'Transmembrane'.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

CPT1A

chr11:68540732

chr8:39607263

ENST00000265641

103_122

580

774.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540732

chr8:39607263

ENST00000265641

48_73

580

774.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540732

chr8:39607263

ENST00000376618

103_122

580

757.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540732

chr8:39607263

ENST00000376618

48_73

580

757.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540732

chr8:39607263

ENST00000539743

103_122

580

774.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540732

chr8:39607263

ENST00000539743

48_73

580

774.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540732

chr8:39607263

ENST00000540367

103_122

580

757.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540732

chr8:39607263

ENST00000540367

48_73

580

757.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540733

chr8:39607263

ENST00000265641

103_122

580

774.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540733

chr8:39607263

ENST00000265641

48_73

580

774.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540733

chr8:39607263

ENST00000376618

103_122

580

757.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540733

chr8:39607263

ENST00000376618

48_73

580

757.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540733

chr8:39607263

ENST00000539743

103_122

580

774.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540733

chr8:39607263

ENST00000539743

48_73

580

774.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540733

chr8:39607263

ENST00000540367

103_122

580

757.0

Transmembrane

Helical

Hgene

CPT1A

chr11:68540733

chr8:39607263

ENST00000540367

48_73

580

757.0

Transmembrane

Helical

Tgene

ADAM2

chr11:68540732

chr8:39607263

ENST00000265708

687_707

788.6666666666666

Transmembrane

Helical

Tgene

ADAM2

chr11:68540732

chr8:39607263

ENST00000347580

687_707

796.3333333333334

Transmembrane

Helical

Tgene

ADAM2

chr11:68540733

chr8:39607263

ENST00000265708

687_707

788.6666666666666

Transmembrane

Helical

Tgene

ADAM2

chr11:68540733

chr8:39607263

ENST00000347580

687_707

796.3333333333334

Transmembrane

Helical

Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.

Hgene	Hchr	Hbp	Henst	Tgene	Tchr	Tbp	Tenst	DeepLoc result
CPT1A	chr11	68540732	ENST00000539743	ADAM2	chr8	39607263	ENST00000265708

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Related Drugs to CPT1A-ADAM2

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 CPT1A-ADAM2

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

	Fusion Gene and Fusion Protein Summary
	Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)
	Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)
	Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)
	Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)
	Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)
	Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)
	Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)
	Potential target of CAR-T therapy development
	Information on the samples that have these potential fusion neoantigens
	Fusion Protein Targeting Drugs - (Manual Curation)
	Fusion Protein Related diseases - (Manual Curation)