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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:FA2H-KARS

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: FA2H-KARS
	FusionPDB ID: 28174
	FusionGDB2.0 ID: 28174
		Hgene	Tgene
	Gene symbol	FA2H	KARS
	Gene ID	79152	3735
	Gene name	fatty acid 2-hydroxylase	lysyl-tRNA synthetase 1
	Synonyms	FAAH\|FAH1\|FAXDC1\|SCS7\|SPG35	CMTRIB\|DFNB89\|KARS\|KARS2\|KRS
	Cytomap	16q23.1	16q23.1
	Type of gene	protein-coding	protein-coding
	Description	fatty acid 2-hydroxylasefatty acid alpha-hydroxylasefatty acid hydroxylase domain containing 1spastic paraplegia 35 (autosomal recessive)	lysine--tRNA ligaselysRSlysine tRNA ligase
	Modification date	20200313	20200318
	UniProtAcc	Q7L5A8	Q15046
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000219368, ENST00000544337,	ENST00000568378, ENST00000302445, ENST00000319410,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	4 X 4 X 3=48	7 X 7 X 4=196
	# samples	5	9
	** MAII score	log2(5/48*10)=0.0588936890535686 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0	log2(9/196*10)=-1.12285674778553 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: FA2H [Title/Abstract] AND KARS [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	FA2H(74773921)-KARS(75665753), # samples:3
Anticipated loss of major functional domain due to fusion event.	FA2H-KARS 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. FA2H-KARS 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. FA2H-KARS 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. FA2H-KARS 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
Hgene	FA2H	GO:0046513	ceramide biosynthetic process	15337768
Tgene	KARS	GO:0000187	activation of MAPK activity	15851690
Tgene	KARS	GO:0002741	positive regulation of cytokine secretion involved in immune response	15851690
Tgene	KARS	GO:0006430	lysyl-tRNA aminoacylation	9278442\|10952987\|23159739
Tgene	KARS	GO:0008285	negative regulation of cell proliferation	15851690
Tgene	KARS	GO:0010759	positive regulation of macrophage chemotaxis	15851690
Tgene	KARS	GO:0015966	diadenosine tetraphosphate biosynthetic process	23159739
Tgene	KARS	GO:0033209	tumor necrosis factor-mediated signaling pathway	15851690
Tgene	KARS	GO:0043032	positive regulation of macrophage activation	15851690
Tgene	KARS	GO:0070374	positive regulation of ERK1 and ERK2 cascade	15851690
Tgene	KARS	GO:1900017	positive regulation of cytokine production involved in inflammatory response	15851690
Tgene	KARS	GO:1900745	positive regulation of p38MAPK cascade	15851690
Tgene	KARS	GO:1905050	positive regulation of metallopeptidase activity	15851690

Fusion gene breakpoints across FA2H (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 KARS (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	ESCA	TCGA-L5-A8NE-01A	FA2H	chr16	74773921	-	KARS	chr16	75665753	-
ChimerDB4	ESCA	TCGA-L5-A8NE	FA2H	chr16	74773920	-	KARS	chr16	75665753	-
ChimerDB4	ESCA	TCGA-L5-A8NE	FA2H	chr16	74773921	-	KARS	chr16	75665753	-

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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)
ENST00000219368	FA2H	chr16	74773921	-	ENST00000319410	KARS	chr16	75665753	-	1483	433	55	1311	418
ENST00000219368	FA2H	chr16	74773921	-	ENST00000302445	KARS	chr16	75665753	-	1483	433	55	1311	418
ENST00000219368	FA2H	chr16	74773920	-	ENST00000319410	KARS	chr16	75665753	-	1483	433	55	1311	418
ENST00000219368	FA2H	chr16	74773920	-	ENST00000302445	KARS	chr16	75665753	-	1483	433	55	1311	418

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
ENST00000219368	ENST00000319410	FA2H	chr16	74773921	-	KARS	chr16	75665753	-	0.004534332	0.9954657
ENST00000219368	ENST00000302445	FA2H	chr16	74773921	-	KARS	chr16	75665753	-	0.004534332	0.9954657
ENST00000219368	ENST00000319410	FA2H	chr16	74773920	-	KARS	chr16	75665753	-	0.004534332	0.9954657
ENST00000219368	ENST00000302445	FA2H	chr16	74773920	-	KARS	chr16	75665753	-	0.004534332	0.9954657

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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

>28174_28174_1_FA2H-KARS_FA2H_chr16_74773920_ENST00000219368_KARS_chr16_75665753_ENST00000302445_length(amino acids)=418AA_BP=126
MRSPAMAPAPPPAASFSPSEVQRRLAAGACWVRRGARLYDLSSFVRHHPGGEQLLRARAGQDISADLDGPPHRHSANARRWLEQYYVGEL
RGEQQGSMENEPVALEETQKTDPAMEPRFKVVDWDKMLVVGGIDRVYEIGRQFRNEGIDLTHNPEFTTCEFYMAYADYHDLMEITEKMVS
GMVKHITGSYKVTYHPDGPEGQAYDVDFTPPFRRINMVEELEKALGMKLPETNLFETEETRKILDDICVAKAVECPPPRTTARLLDKLVG
EFLEVTCINPTFICDHPQIMSPLAKWHRSKEGLTERFELFVMKKEICNAYTELNDPMRQRQLFEEQAKAKAAGDDEAMFIDENFCTALEY

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

>28174_28174_2_FA2H-KARS_FA2H_chr16_74773920_ENST00000219368_KARS_chr16_75665753_ENST00000319410_length(amino acids)=418AA_BP=126
MRSPAMAPAPPPAASFSPSEVQRRLAAGACWVRRGARLYDLSSFVRHHPGGEQLLRARAGQDISADLDGPPHRHSANARRWLEQYYVGEL
RGEQQGSMENEPVALEETQKTDPAMEPRFKVVDWDKMLVVGGIDRVYEIGRQFRNEGIDLTHNPEFTTCEFYMAYADYHDLMEITEKMVS
GMVKHITGSYKVTYHPDGPEGQAYDVDFTPPFRRINMVEELEKALGMKLPETNLFETEETRKILDDICVAKAVECPPPRTTARLLDKLVG
EFLEVTCINPTFICDHPQIMSPLAKWHRSKEGLTERFELFVMKKEICNAYTELNDPMRQRQLFEEQAKAKAAGDDEAMFIDENFCTALEY

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

>28174_28174_3_FA2H-KARS_FA2H_chr16_74773921_ENST00000219368_KARS_chr16_75665753_ENST00000302445_length(amino acids)=418AA_BP=126
MRSPAMAPAPPPAASFSPSEVQRRLAAGACWVRRGARLYDLSSFVRHHPGGEQLLRARAGQDISADLDGPPHRHSANARRWLEQYYVGEL
RGEQQGSMENEPVALEETQKTDPAMEPRFKVVDWDKMLVVGGIDRVYEIGRQFRNEGIDLTHNPEFTTCEFYMAYADYHDLMEITEKMVS
GMVKHITGSYKVTYHPDGPEGQAYDVDFTPPFRRINMVEELEKALGMKLPETNLFETEETRKILDDICVAKAVECPPPRTTARLLDKLVG
EFLEVTCINPTFICDHPQIMSPLAKWHRSKEGLTERFELFVMKKEICNAYTELNDPMRQRQLFEEQAKAKAAGDDEAMFIDENFCTALEY

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

>28174_28174_4_FA2H-KARS_FA2H_chr16_74773921_ENST00000219368_KARS_chr16_75665753_ENST00000319410_length(amino acids)=418AA_BP=126
MRSPAMAPAPPPAASFSPSEVQRRLAAGACWVRRGARLYDLSSFVRHHPGGEQLLRARAGQDISADLDGPPHRHSANARRWLEQYYVGEL
RGEQQGSMENEPVALEETQKTDPAMEPRFKVVDWDKMLVVGGIDRVYEIGRQFRNEGIDLTHNPEFTTCEFYMAYADYHDLMEITEKMVS
GMVKHITGSYKVTYHPDGPEGQAYDVDFTPPFRRINMVEELEKALGMKLPETNLFETEETRKILDDICVAKAVECPPPRTTARLLDKLVG
EFLEVTCINPTFICDHPQIMSPLAKWHRSKEGLTERFELFVMKKEICNAYTELNDPMRQRQLFEEQAKAKAAGDDEAMFIDENFCTALEY

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

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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/chr16:74773921/chr16:75665753)
- 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
FA2H Q7L5A8	KARS Q15046
FUNCTION: Catalyzes the hydroxylation of free fatty acids at the C-2 position to produce 2-hydroxy fatty acids, which are building blocks of sphingolipids and glycosphingolipids common in neural tissue and epidermis (PubMed:15337768, PubMed:15863841, PubMed:17355976, PubMed:22517924). FA2H is stereospecific for the production of (R)-2-hydroxy fatty acids (PubMed:22517924). Plays an essential role in the synthesis of galactosphingolipids of the myelin sheath (By similarity). Responsible for the synthesis of sphingolipids and glycosphingolipids involved in the formation of epidermal lamellar bodies critical for skin permeability barrier (PubMed:17355976). Participates in the synthesis of glycosphingolipids and a fraction of type II wax diesters in sebaceous gland, specifically regulating hair follicle homeostasis (By similarity). Involved in the synthesis of sphingolipids of plasma membrane rafts, controlling lipid raft mobility and trafficking of raft-associated proteins (By similarity). {ECO:0000250\|UniProtKB:Q5MPP0, ECO:0000269\|PubMed:15337768, ECO:0000269\|PubMed:15863841, ECO:0000269\|PubMed:17355976, ECO:0000269\|PubMed:22517924}.	FUNCTION: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:9278442, PubMed:18029264, PubMed:18272479). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:5338216, PubMed:14975237, PubMed:19524539, PubMed:23159739). {ECO:0000269\|PubMed:14975237, ECO:0000269\|PubMed:15851690, ECO:0000269\|PubMed:18029264, ECO:0000269\|PubMed:19524539, ECO:0000269\|PubMed:28887846, ECO:0000269\|PubMed:5338216, ECO:0000269\|PubMed:9278442}.; FUNCTION: (Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. {ECO:0000269\|PubMed:15220430}.

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

FA2H

chr16:74773920

chr16:75665753

ENST00000219368

8_86

121.0

373.0

Domain

Cytochrome b5 heme-binding

Hgene

FA2H

chr16:74773921

chr16:75665753

ENST00000219368

8_86

121.0

373.0

Domain

Cytochrome b5 heme-binding

Tgene

KARS

chr16:74773920

chr16:75665753

ENST00000302445

323_325

305.0

598.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773920

chr16:75665753

ENST00000302445

331_332

305.0

598.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773920

chr16:75665753

ENST00000302445

494_495

305.0

598.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773920

chr16:75665753

ENST00000302445

550_553

305.0

598.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773920

chr16:75665753

ENST00000319410

331_332

333.0

626.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773920

chr16:75665753

ENST00000319410

494_495

333.0

626.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773920

chr16:75665753

ENST00000319410

550_553

333.0

626.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773921

chr16:75665753

ENST00000302445

323_325

305.0

598.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773921

chr16:75665753

ENST00000302445

331_332

305.0

598.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773921

chr16:75665753

ENST00000302445

494_495

305.0

598.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773921

chr16:75665753

ENST00000302445

550_553

305.0

598.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773921

chr16:75665753

ENST00000319410

331_332

333.0

626.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773921

chr16:75665753

ENST00000319410

494_495

333.0

626.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773921

chr16:75665753

ENST00000319410

550_553

333.0

626.0

Nucleotide binding

ATP

- 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

FA2H

chr16:74773920

chr16:75665753

ENST00000219368

219_361

121.0

373.0

Domain

Fatty acid hydroxylase

Hgene

FA2H

chr16:74773921

chr16:75665753

ENST00000219368

219_361

121.0

373.0

Domain

Fatty acid hydroxylase

Hgene

FA2H

chr16:74773920

chr16:75665753

ENST00000219368

168_188

121.0

373.0

Transmembrane

Helical

Hgene

FA2H

chr16:74773920

chr16:75665753

ENST00000219368

213_233

121.0

373.0

Transmembrane

Helical

Hgene

FA2H

chr16:74773920

chr16:75665753

ENST00000219368

268_288

121.0

373.0

Transmembrane

Helical

Hgene

FA2H

chr16:74773920

chr16:75665753

ENST00000219368

290_310

121.0

373.0

Transmembrane

Helical

Hgene

FA2H

chr16:74773921

chr16:75665753

ENST00000219368

168_188

121.0

373.0

Transmembrane

Helical

Hgene

FA2H

chr16:74773921

chr16:75665753

ENST00000219368

213_233

121.0

373.0

Transmembrane

Helical

Hgene

FA2H

chr16:74773921

chr16:75665753

ENST00000219368

268_288

121.0

373.0

Transmembrane

Helical

Hgene

FA2H

chr16:74773921

chr16:75665753

ENST00000219368

290_310

121.0

373.0

Transmembrane

Helical

Tgene

KARS

chr16:74773920

chr16:75665753

ENST00000319410

323_325

333.0

626.0

Nucleotide binding

ATP

Tgene

KARS

chr16:74773921

chr16:75665753

ENST00000319410

323_325

333.0

626.0

Nucleotide binding

ATP

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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 >>>862_FA2H_74773921_KARS_75665753_862_FA2H_74773921_KARS_75665753_ranked_0.pdb	FA2H	74773920	74773921	ENST00000302445	KARS	chr16	75665753	-	MRSPAMAPAPPPAASFSPSEVQRRLAAGACWVRRGARLYDLSSFVRHHPGGEQLLRARAGQDISADLDGPPHRHSANARRWLEQYYVGEL RGEQQGSMENEPVALEETQKTDPAMEPRFKVVDWDKMLVVGGIDRVYEIGRQFRNEGIDLTHNPEFTTCEFYMAYADYHDLMEITEKMVS GMVKHITGSYKVTYHPDGPEGQAYDVDFTPPFRRINMVEELEKALGMKLPETNLFETEETRKILDDICVAKAVECPPPRTTARLLDKLVG EFLEVTCINPTFICDHPQIMSPLAKWHRSKEGLTERFELFVMKKEICNAYTELNDPMRQRQLFEEQAKAKAAGDDEAMFIDENFCTALEY	418

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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.

FA2H_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
FA2H
KARS

- 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 FA2H-KARS

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 FA2H-KARS

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