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Fusion Protein:LAP3-SERPINA1

Fusion Gene and Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: LAP3-SERPINA1
	FusionPDB ID: 44039
	FusionGDB2.0 ID: 44039
		Hgene	Tgene
	Gene symbol	LAP3	SERPINA1
	Gene ID	51056	5265
	Gene name	leucine aminopeptidase 3	serpin family A member 1
	Synonyms	HEL-S-106\|LAP\|LAPEP\|PEPS	A1A\|A1AT\|AAT\|PI\|PI1\|PRO2275\|alpha1AT\|nNIF
	Cytomap	4p15.32	14q32.13
	Type of gene	protein-coding	protein-coding
	Description	cytosol aminopeptidaseLAP-3epididymis secretory protein Li 106leucyl aminopeptidasepeptidase Sproline aminopeptidaseprolyl aminopeptidase	alpha-1-antitrypsinalpha-1 antitrypsinalpha-1 protease inhibitoralpha-1-antiproteinasealpha-1-antitrypsin nullalpha-1-antitrypsin short transcript variant 1C4alpha-1-antitrypsin short transcript variant 1C5epididymis secretory sperm binding protein
	Modification date	20200313	20200327
	UniProtAcc	P28838 Main function of 5'-partner protein: FUNCTION: Cytolosic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides. The presence of Zn(2+) ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme. For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates. Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status. {ECO:0000250\|UniProtKB:P00727}.	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000226299, ENST00000606142, ENST00000503467,	ENST00000555289, ENST00000402629, ENST00000355814, ENST00000393087, ENST00000393088, ENST00000404814, ENST00000437397, ENST00000440909, ENST00000448921, ENST00000449399,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	4 X 4 X 3=48	16 X 17 X 6=1632
	# samples	5	18
	** MAII score	log2(5/48*10)=0.0588936890535686 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0	log2(18/1632*10)=-3.18057224564182 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Fusion gene context	PubMed: LAP3 [Title/Abstract] AND SERPINA1 [Title/Abstract] AND fusion [Title/Abstract]
Fusion neoantigen context	PubMed: LAP3 [Title/Abstract] AND SERPINA1 [Title/Abstract] AND neoantigen [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	LAP3(17585220)-SERPINA1(94845846), # samples:1
Anticipated loss of major functional domain due to fusion event.	LAP3-SERPINA1 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. LAP3-SERPINA1 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. LAP3-SERPINA1 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. LAP3-SERPINA1 seems lost the major protein functional domain in Hgene 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

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr4:17585220/chr14:94845846)
- 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 LAP3 (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 SERPINA1 (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)
ENST00000226299	LAP3	chr4	17585220	+	ENST00000440909	SERPINA1	chr14	94845846	-	2638	698	184	708	174
ENST00000226299	LAP3	chr4	17585220	+	ENST00000448921	SERPINA1	chr14	94845846	-	2638	698	184	708	174
ENST00000226299	LAP3	chr4	17585220	+	ENST00000437397	SERPINA1	chr14	94845846	-	2638	698	184	708	174
ENST00000226299	LAP3	chr4	17585220	+	ENST00000355814	SERPINA1	chr14	94845846	-	2638	698	184	708	174
ENST00000226299	LAP3	chr4	17585220	+	ENST00000393087	SERPINA1	chr14	94845846	-	1036	698	184	708	174
ENST00000226299	LAP3	chr4	17585220	+	ENST00000393088	SERPINA1	chr14	94845846	-	1009	698	184	708	174
ENST00000226299	LAP3	chr4	17585220	+	ENST00000404814	SERPINA1	chr14	94845846	-	996	698	184	708	174
ENST00000226299	LAP3	chr4	17585220	+	ENST00000449399	SERPINA1	chr14	94845846	-	936	698	184	708	174
ENST00000606142	LAP3	chr4	17585220	+	ENST00000440909	SERPINA1	chr14	94845846	-	2335	395	1354	1761	135
ENST00000606142	LAP3	chr4	17585220	+	ENST00000448921	SERPINA1	chr14	94845846	-	2335	395	1354	1761	135
ENST00000606142	LAP3	chr4	17585220	+	ENST00000437397	SERPINA1	chr14	94845846	-	2335	395	1354	1761	135
ENST00000606142	LAP3	chr4	17585220	+	ENST00000355814	SERPINA1	chr14	94845846	-	2335	395	1354	1761	135
ENST00000606142	LAP3	chr4	17585220	+	ENST00000393087	SERPINA1	chr14	94845846	-	733	395	19	405	128
ENST00000606142	LAP3	chr4	17585220	+	ENST00000393088	SERPINA1	chr14	94845846	-	706	395	19	405	128
ENST00000606142	LAP3	chr4	17585220	+	ENST00000404814	SERPINA1	chr14	94845846	-	693	395	19	405	128
ENST00000606142	LAP3	chr4	17585220	+	ENST00000449399	SERPINA1	chr14	94845846	-	633	395	19	405	128

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
ENST00000226299	ENST00000440909	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.016752038	0.983248
ENST00000226299	ENST00000448921	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.016752038	0.983248
ENST00000226299	ENST00000437397	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.016752038	0.983248
ENST00000226299	ENST00000355814	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.016752038	0.983248
ENST00000226299	ENST00000393087	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.02092983	0.9790702
ENST00000226299	ENST00000393088	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.022197299	0.97780275
ENST00000226299	ENST00000404814	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.02180666	0.9781934
ENST00000226299	ENST00000449399	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.024312917	0.975687
ENST00000606142	ENST00000440909	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.7843627	0.2156373
ENST00000606142	ENST00000448921	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.7843627	0.2156373
ENST00000606142	ENST00000437397	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.7843627	0.2156373
ENST00000606142	ENST00000355814	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.7843627	0.2156373
ENST00000606142	ENST00000393087	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.025470557	0.97452945
ENST00000606142	ENST00000393088	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.02652986	0.9734701
ENST00000606142	ENST00000404814	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.02601245	0.9739875
ENST00000606142	ENST00000449399	LAP3	chr4	17585220	+	SERPINA1	chr14	94845846	-	0.02540076	0.9745993

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 LAP3-SERPINA1

+/-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

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Potential FusionNeoAntigen Information of LAP3-SERPINA1 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.

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)

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Potential FusionNeoAntigen Information of LAP3-SERPINA1 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 LAP3-SERPINA1

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LAP3-SERPINA1

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

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Vaccine Design for the FusionNeoAntigens of LAP3-SERPINA1

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

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 LAP3-SERPINA1

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

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Potential target of CAR-T therapy development for LAP3-SERPINA1

Predicted 3D structure. We used RoseTTAFold.

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

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

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Related Drugs to LAP3-SERPINA1

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 LAP3-SERPINA1

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)