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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
	Related Diseases

Fusion gene:METTL5-GGPS1 (FusionGDB2 ID:HG29081TG9453)

Fusion Gene Summary for METTL5-GGPS1

Fusion gene summary

Fusion gene information	Fusion gene name: METTL5-GGPS1
	Fusion gene ID: hg29081tg9453
		Hgene	Tgene
	Gene symbol	METTL5	GGPS1
	Gene ID	29081	9453
	Gene name	methyltransferase like 5	geranylgeranyl diphosphate synthase 1
	Synonyms	HSPC133\|MRT72	GGPPS\|GGPPS1
	Cytomap	('METTL5')('GGPS1') 2q31.1	1q42.3
	Type of gene	protein-coding	protein-coding
	Description	methyltransferase-like protein 5	geranylgeranyl pyrophosphate synthase(2E,6E)-farnesyl diphosphate synthaseGGPP synthaseGGPPSasedimethylallyltranstransferasefarnesyl diphosphate synthasefarnesyltranstransferasegeranyltranstransferase
	Modification date	20200327	20200313
	UniProtAcc	.	O95749
	Ensembl transtripts involved in fusion gene	ENST00000260953, ENST00000308099, ENST00000392640, ENST00000409340, ENST00000409837, ENST00000409965, ENST00000410097,
Fusion gene scores	* DoF score	4 X 6 X 4=96	5 X 3 X 3=45
	# samples	7	6
	** MAII score	log2(7/96*10)=-0.45567948377619 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(6/45*10)=0.415037499278844 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Context	PubMed: METTL5 [Title/Abstract] AND GGPS1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	METTL5(170680999)-GGPS1(235498557), # samples:1
Anticipated loss of major functional domain due to fusion event.

* 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	GGPS1	GO:0006720	isoprenoid metabolic process	10026212

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-BR-8284-01A	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+

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Fusion Gene ORF analysis for METTL5-GGPS1

Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.

ORF	Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
5CDS-5UTR	ENST00000260953	ENST00000282841	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000260953	ENST00000358966	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000260953	ENST00000476121	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000260953	ENST00000488594	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000308099	ENST00000282841	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000308099	ENST00000358966	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000308099	ENST00000476121	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000308099	ENST00000488594	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000392640	ENST00000282841	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000392640	ENST00000358966	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000392640	ENST00000476121	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000392640	ENST00000488594	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409340	ENST00000282841	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409340	ENST00000358966	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409340	ENST00000476121	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409340	ENST00000488594	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409837	ENST00000282841	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409837	ENST00000358966	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409837	ENST00000476121	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409837	ENST00000488594	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409965	ENST00000282841	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409965	ENST00000358966	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409965	ENST00000476121	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000409965	ENST00000488594	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000410097	ENST00000282841	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000410097	ENST00000358966	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000410097	ENST00000476121	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-5UTR	ENST00000410097	ENST00000488594	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000260953	ENST00000391855	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000260953	ENST00000489692	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000308099	ENST00000391855	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000308099	ENST00000489692	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000392640	ENST00000391855	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000392640	ENST00000489692	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000409340	ENST00000391855	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000409340	ENST00000489692	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000409837	ENST00000391855	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000409837	ENST00000489692	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000409965	ENST00000391855	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000409965	ENST00000489692	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000410097	ENST00000391855	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+
5CDS-intron	ENST00000410097	ENST00000489692	METTL5	chr2	170680999	-	GGPS1	chr1	235498557	+

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

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)

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

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Fusion Genomic Features for METTL5-GGPS1

FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for METTL5-GGPS1

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:170680999/:235498557)
- 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
.	GGPS1 O95749
FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.	FUNCTION: Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.

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.

- In-frame and 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

- In-frame and 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

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Fusion Gene Sequence for METTL5-GGPS1

For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for METTL5-GGPS1

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 (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- Retained PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

- Retained PPIs, but lost function due to frame-shift fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs for METTL5-GGPS1

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner	Gene	UniProtAcc	DrugBank ID	Drug name	Drug activity	Drug type	Drug status
Tgene	GGPS1	O95749	DB00282	Pamidronic acid	Inhibitor	Small molecule	Approved
Tgene	GGPS1	O95749	DB00399	Zoledronic acid	Inhibitor	Small molecule	Approved
Tgene	GGPS1	O95749	DB00710	Ibandronate	Inhibitor	Small molecule	Approved\|Investigational

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Related Diseases for METTL5-GGPS1

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner	Gene	Disease ID	Disease name	# pubmeds	Source
Hgene	METTL5	C0025958	Microcephaly	1	GENOMICS_ENGLAND
Hgene	METTL5	C0233514	Abnormal behavior	1	GENOMICS_ENGLAND
Hgene	METTL5	C0454644	Delayed speech and language development	1	GENOMICS_ENGLAND
Hgene	METTL5	C3714756	Intellectual Disability	1	GENOMICS_ENGLAND

Fusion Gene Studies in Kim Lab

Fusion gene:METTL5-GGPS1 (FusionGDB2 ID:HG29081TG9453)

Fusion Gene Summary for METTL5-GGPS1

Fusion Gene ORF analysis for METTL5-GGPS1

Fusion Genomic Features for METTL5-GGPS1

Fusion Protein Features for METTL5-GGPS1

Fusion Gene Sequence for METTL5-GGPS1

Fusion Gene PPI Analysis for METTL5-GGPS1

Related Drugs for METTL5-GGPS1

Related Diseases for METTL5-GGPS1

Fusion Gene Studies
in Kim Lab