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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:HMGCS2-SF3B1

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: HMGCS2-SF3B1
	FusionPDB ID: 36927
	FusionGDB2.0 ID: 36927
		Hgene	Tgene
	Gene symbol	HMGCS2	SF3B1
	Gene ID	3158	23451
	Gene name	3-hydroxy-3-methylglutaryl-CoA synthase 2	splicing factor 3b subunit 1
	Synonyms	-	Hsh155\|MDS\|PRP10\|PRPF10\|SAP155\|SF3b155
	Cytomap	1p12	2q33.1
	Type of gene	protein-coding	protein-coding
	Description	hydroxymethylglutaryl-CoA synthase, mitochondrial3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial)HMG-CoA synthasetesticular tissue protein Li 88	splicing factor 3B subunit 1pre-mRNA processing 10pre-mRNA splicing factor SF3b, 155 kDa subunitspliceosome-associated protein 155splicing factor 3b, subunit 1, 155kDa
	Modification date	20200313	20200329
	UniProtAcc	P54868	.
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000369406, ENST00000544913, ENST00000476640,	ENST00000409915, ENST00000414963, ENST00000462613, ENST00000487698, ENST00000335508,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	2 X 1 X 2=4	6 X 8 X 4=192
	# samples	2	9
	** MAII score	log2(2/4*10)=2.32192809488736	log2(9/192*10)=-1.09310940439148 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: HMGCS2 [Title/Abstract] AND SF3B1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	HMGCS2(120298049)-SF3B1(198257912), # samples:1
Anticipated loss of major functional domain due to fusion event.	HMGCS2-SF3B1 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. HMGCS2-SF3B1 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. HMGCS2-SF3B1 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. HMGCS2-SF3B1 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	SF3B1	GO:0000398	mRNA splicing, via spliceosome	11252167\|28781166\|29360106

Fusion gene breakpoints across HMGCS2 (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 SF3B1 (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	STAD	TCGA-CD-8532	HMGCS2	chr1	120298049	-	SF3B1	chr2	198257912	-

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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)
ENST00000369406	HMGCS2	chr1	120298049	-	ENST00000335508	SF3B1	chr2	198257912	-	4132	1237	32	1612	526
ENST00000544913	HMGCS2	chr1	120298049	-	ENST00000335508	SF3B1	chr2	198257912	-	4017	1122	43	1497	484

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
ENST00000369406	ENST00000335508	HMGCS2	chr1	120298049	-	SF3B1	chr2	198257912	-	0.000147448	0.99985254
ENST00000544913	ENST00000335508	HMGCS2	chr1	120298049	-	SF3B1	chr2	198257912	-	0.000196756	0.99980325

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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

>36927_36927_1_HMGCS2-SF3B1_HMGCS2_chr1_120298049_ENST00000369406_SF3B1_chr2_198257912_ENST00000335508_length(amino acids)=526AA_BP=402
MLAPLEMQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFSTASAVPLAKTDTWPKDVGILALEVYFPAQYVDQTDLEKYNNVEAGKY
TVGLGQTRMGFCSVQEDINSLCLTVVQRLMERIQLPWDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGIDTTNACYGGTASLF
NAANWMESSSWDGRYAMVVCGDIAVYPSGNARPTGGAGAVAMLIGPKAPLALERGLRGTHMENVYDFYKPNLASEYPIVDGKLSIQCYLR
ALDRCYTSYRKKIQNQWKQAGSDRPFTLDDLQYMIFHTPFCKMVQKSLARLMFNDFLSASSDTQTSLYKGLEAFGGLKLEDTYTNKDLDK
ALLKASQDMFDKKTKASLYLSTHNGNMYTSSLYGCLASLLSQDLVHRQTASAVVQHMSLGVYGFGCEDSLNHLLNYVWPNVFETSPHVIQ

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

>36927_36927_2_HMGCS2-SF3B1_HMGCS2_chr1_120298049_ENST00000544913_SF3B1_chr2_198257912_ENST00000335508_length(amino acids)=484AA_BP=360
MLAPLEMQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFSTASAVPLAKTDTWPKDVGILALEVYFPAQYVDQTDLEKYNNVEAGKY
TVGLGQTRMGFCSVQEDINSLCLTVVQRLMERIQLPWDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGIDTTNACYGGTASLF
NAANWMESSSWDGLRGTHMENVYDFYKPNLASEYPIVDGKLSIQCYLRALDRCYTSYRKKIQNQWKQAGSDRPFTLDDLQYMIFHTPFCK
MVQKSLARLMFNDFLSASSDTQTSLYKGLEAFGGLKLEDTYTNKDLDKALLKASQDMFDKKTKASLYLSTHNGNMYTSSLYGCLASLLSQ
DLVHRQTASAVVQHMSLGVYGFGCEDSLNHLLNYVWPNVFETSPHVIQAVMGALEGLRVAIGPCRMLQYCLQGLFHPARKVRDVYWKIYN

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

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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/chr1:120298049/chr2:198257912)
- 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
HMGCS2 P54868	.
FUNCTION: Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate. {ECO:0000269\|PubMed:11228257, ECO:0000269\|PubMed:23751782, ECO:0000269\|PubMed:29597274}.	FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

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

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

1010_1048

88.0

Repeat

Note=HEAT 8

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

1052_1090

88.0

Repeat

Note=HEAT 9

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

1122_1160

88.0

Repeat

Note=HEAT 10

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

1163_1201

88.0

Repeat

Note=HEAT 11

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

569_603

88.0

Repeat

Note=HEAT 2

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

604_641

88.0

Repeat

Note=HEAT 3

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

643_677

88.0

Repeat

Note=HEAT 4

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

680_718

88.0

Repeat

Note=HEAT 5

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

763_801

88.0

Repeat

Note=HEAT 6

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000409915

843_881

88.0

Repeat

Note=HEAT 7

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

1010_1048

145.0

Repeat

Note=HEAT 8

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

1052_1090

145.0

Repeat

Note=HEAT 9

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

1122_1160

145.0

Repeat

Note=HEAT 10

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

1163_1201

145.0

Repeat

Note=HEAT 11

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

569_603

145.0

Repeat

Note=HEAT 2

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

604_641

145.0

Repeat

Note=HEAT 3

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

643_677

145.0

Repeat

Note=HEAT 4

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

680_718

145.0

Repeat

Note=HEAT 5

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

763_801

145.0

Repeat

Note=HEAT 6

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000414963

843_881

145.0

Repeat

Note=HEAT 7

- 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

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

1010_1048

1179.6666666666667

1305.0

Repeat

Note=HEAT 8

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

1052_1090

1179.6666666666667

1305.0

Repeat

Note=HEAT 9

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

1122_1160

1179.6666666666667

1305.0

Repeat

Note=HEAT 10

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

1163_1201

1179.6666666666667

1305.0

Repeat

Note=HEAT 11

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

569_603

1179.6666666666667

1305.0

Repeat

Note=HEAT 2

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

604_641

1179.6666666666667

1305.0

Repeat

Note=HEAT 3

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

643_677

1179.6666666666667

1305.0

Repeat

Note=HEAT 4

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

680_718

1179.6666666666667

1305.0

Repeat

Note=HEAT 5

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

763_801

1179.6666666666667

1305.0

Repeat

Note=HEAT 6

Tgene

SF3B1

chr1:120298049

chr2:198257912

ENST00000335508

843_881

1179.6666666666667

1305.0

Repeat

Note=HEAT 7

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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
HMGCS2
SF3B1

- 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
Tgene	SF3B1	chr1:120298049	chr2:198257912	ENST00000335508		22	25	1156_1157	1179.6666666666667	1305.0	PHF5A
Tgene	SF3B1	chr1:120298049	chr2:198257912	ENST00000335508		22	25	547_550	1179.6666666666667	1305.0	PHF5A
Tgene	SF3B1	chr1:120298049	chr2:198257912	ENST00000335508		22	25	223_491	1179.6666666666667	1305.0	PPP1R8
Tgene	SF3B1	chr1:120298049	chr2:198257912	ENST00000335508		22	25	529_568	1179.6666666666667	1305.0	SF3B14

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Related Drugs to HMGCS2-SF3B1

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 HMGCS2-SF3B1

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