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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:EIF2S1-GPHN

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: EIF2S1-GPHN
	FusionPDB ID: 25729
	FusionGDB2.0 ID: 25729
		Hgene	Tgene
	Gene symbol	EIF2S1	GPHN
	Gene ID	1965	10243
	Gene name	eukaryotic translation initiation factor 2 subunit alpha	gephyrin
	Synonyms	EIF-2\|EIF-2A\|EIF-2alpha\|EIF2\|EIF2A	GEPH\|GPH\|GPHRYN\|HKPX1\|MOCODC
	Cytomap	14q23.3	14q23.3-q24.1
	Type of gene	protein-coding	protein-coding
	Description	eukaryotic translation initiation factor 2 subunit 1eIF-2-alphaeukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa	gephyrin
	Modification date	20200313	20200313
	UniProtAcc	P05198	Q9NQX3
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000256383, ENST00000466499,	ENST00000544752, ENST00000305960, ENST00000459628, ENST00000543237, ENST00000315266, ENST00000478722,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	4 X 5 X 5=100	42 X 51 X 15=32130
	# samples	8	62
	** MAII score	log2(8/100*10)=-0.321928094887362 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(62/32130*10)=-5.69550895508454 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: EIF2S1 [Title/Abstract] AND GPHN [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	EIF2S1(67827173)-GPHN(67576857), # samples:3 GPHN(67147903)-EIF2S1(67831484), # samples:1
Anticipated loss of major functional domain due to fusion event.	EIF2S1-GPHN 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. EIF2S1-GPHN 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. EIF2S1-GPHN 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. EIF2S1-GPHN 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	GPHN	GO:0032324	molybdopterin cofactor biosynthetic process	26613940
Tgene	GPHN	GO:0097112	gamma-aminobutyric acid receptor clustering	26613940

Fusion gene breakpoints across EIF2S1 (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 GPHN (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	BRCA	TCGA-GM-A2DB-01A	EIF2S1	chr14	67841264	-	GPHN	chr14	67291192	+
ChimerDB4	BRCA	TCGA-GM-A2DB-01A	EIF2S1	chr14	67841264	+	GPHN	chr14	67291192	+
ChimerDB4	ESCA	TCGA-LN-A5U5-01A	EIF2S1	chr14	67827173	-	GPHN	chr14	67576857	+
ChimerDB4	ESCA	TCGA-LN-A5U5-01A	EIF2S1	chr14	67827173	+	GPHN	chr14	67576857	+
ChimerDB4	ESCA	TCGA-LN-A5U5	EIF2S1	chr14	67827173	+	GPHN	chr14	67576856	+
ChimerDB4	ESCA	TCGA-LN-A5U5	EIF2S1	chr14	67827173	+	GPHN	chr14	67576857	+
ChimerDB4	STAD	TCGA-LN-A5U5-01A3	EIF2S1	chr14	67827172	+	GPHN	chr14	67576856	+

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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)

ENST00000256383

EIF2S1

chr14

67841264

ENST00000315266

GPHN

chr14

67291192

3653

782

461

2791

776

ENST00000256383

EIF2S1

chr14

67841264

ENST00000478722

GPHN

chr14

67291192

3757

782

461

2890

809

ENST00000466499

EIF2S1

chr14

67841264

ENST00000315266

GPHN

chr14

67291192

3952

1081

760

3090

776

ENST00000466499

EIF2S1

chr14

67841264

ENST00000478722

GPHN

chr14

67291192

4056

1081

760

3189

809

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
ENST00000256383	ENST00000315266	EIF2S1	chr14	67841264	+	GPHN	chr14	67291192	+	0.002428031	0.997572
ENST00000256383	ENST00000478722	EIF2S1	chr14	67841264	+	GPHN	chr14	67291192	+	0.002038626	0.9979614
ENST00000466499	ENST00000315266	EIF2S1	chr14	67841264	+	GPHN	chr14	67291192	+	0.001734447	0.99826556
ENST00000466499	ENST00000478722	EIF2S1	chr14	67841264	+	GPHN	chr14	67291192	+	0.001429208	0.9985708

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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

>25729_25729_1_EIF2S1-GPHN_EIF2S1_chr14_67841264_ENST00000256383_GPHN_chr14_67291192_ENST00000315266_length(amino acids)=776AA_BP=107
MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSINKLIRIGRNECVVVIRVDKEKGYIDLSKRRV
SPEEAIKCEDKFTKSKTETLIDWCDEKELNLILTTGGTGFAPRDVTPEATKEVIEREAPGMALAMLMGSLNVTPLGMLSRPVCGIRGKTL
IINLPGSKKGSQECFQFILPALPHAIDLLRDAIVKVKEVHDELEDLPSPPPPLSPPPTTSPHKQTEDKGVQCEEEEEEKKDSGVASTEDS
SSSHITAAAIAAKIPDSIISRGVQVLPRDTASLSTTPSESPRAQATSRLSTASCPTPKVQSRCSSKENILRASHSAVDITKVARRHRMSP
FPLTSMDKAFITVLEMTPVLGTEIINYRDGMGRVLAQDVYAKDNLPPFPASVKDGYAVRAADGPGDRFIIGESQAGEQPTQTVMPGQVMR
VTTGAPIPCGADAVVQVEDTELIRESDDGTEELEVRILVQARPGQDIRPIGHDIKRGECVLAKGTHMGPSEIGLLATVGVTEVEVNKFPV
VAVMSTGNELLNPEDDLLPGKIRDSNRSTLLATIQEHGYPTINLGIVGDNPDDLLNALNEGISRADVIITSGGVSMGEKDYLKQVLDIDL
HAQIHFGRVFMKPGLPTTFATLDIDGVRKIIFALPGNPVSAVVTCNLFVVPALRKMQGILDPRPTIIKARLSCDVKLDPRPEYHRCILTW

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

>25729_25729_2_EIF2S1-GPHN_EIF2S1_chr14_67841264_ENST00000256383_GPHN_chr14_67291192_ENST00000478722_length(amino acids)=809AA_BP=107
MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSINKLIRIGRNECVVVIRVDKEKGYIDLSKRRV
SPEEAIKCEDKFTKSKTETLIDWCDEKELNLILTTGGTGFAPRDVTPEATKEVIEREAPGMALAMLMGSLNVTPLGMLSRPVCGIRGKTL
IINLPGSKKGSQECFQFILPALPHAIDLLRDAIVKVKEVHDELEDLPSPPPPLSPPPTTSPHKQTEDKGVQCEEEEEEKKDSGVASTEDS
SSSHITAAAIAAKKHPFYTSPAVVMAHGEQPIPGLINYSHHSTDERIPDSIISRGVQVLPRDTASLSTTPSESPRAQATSRLSTASCPTP
KVQSRCSSKENILRASHSAVDITKVARRHRMSPFPLTSMDKAFITVLEMTPVLGTEIINYRDGMGRVLAQDVYAKDNLPPFPASVKDGYA
VRAADGPGDRFIIGESQAGEQPTQTVMPGQVMRVTTGAPIPCGADAVVQVEDTELIRESDDGTEELEVRILVQARPGQDIRPIGHDIKRG
ECVLAKGTHMGPSEIGLLATVGVTEVEVNKFPVVAVMSTGNELLNPEDDLLPGKIRDSNRSTLLATIQEHGYPTINLGIVGDNPDDLLNA
LNEGISRADVIITSGGVSMGEKDYLKQVLDIDLHAQIHFGRVFMKPGLPTTFATLDIDGVRKIIFALPGNPVSAVVTCNLFVVPALRKMQ

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

>25729_25729_3_EIF2S1-GPHN_EIF2S1_chr14_67841264_ENST00000466499_GPHN_chr14_67291192_ENST00000315266_length(amino acids)=776AA_BP=107
MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSINKLIRIGRNECVVVIRVDKEKGYIDLSKRRV
SPEEAIKCEDKFTKSKTETLIDWCDEKELNLILTTGGTGFAPRDVTPEATKEVIEREAPGMALAMLMGSLNVTPLGMLSRPVCGIRGKTL
IINLPGSKKGSQECFQFILPALPHAIDLLRDAIVKVKEVHDELEDLPSPPPPLSPPPTTSPHKQTEDKGVQCEEEEEEKKDSGVASTEDS
SSSHITAAAIAAKIPDSIISRGVQVLPRDTASLSTTPSESPRAQATSRLSTASCPTPKVQSRCSSKENILRASHSAVDITKVARRHRMSP
FPLTSMDKAFITVLEMTPVLGTEIINYRDGMGRVLAQDVYAKDNLPPFPASVKDGYAVRAADGPGDRFIIGESQAGEQPTQTVMPGQVMR
VTTGAPIPCGADAVVQVEDTELIRESDDGTEELEVRILVQARPGQDIRPIGHDIKRGECVLAKGTHMGPSEIGLLATVGVTEVEVNKFPV
VAVMSTGNELLNPEDDLLPGKIRDSNRSTLLATIQEHGYPTINLGIVGDNPDDLLNALNEGISRADVIITSGGVSMGEKDYLKQVLDIDL
HAQIHFGRVFMKPGLPTTFATLDIDGVRKIIFALPGNPVSAVVTCNLFVVPALRKMQGILDPRPTIIKARLSCDVKLDPRPEYHRCILTW

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

>25729_25729_4_EIF2S1-GPHN_EIF2S1_chr14_67841264_ENST00000466499_GPHN_chr14_67291192_ENST00000478722_length(amino acids)=809AA_BP=107
MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSINKLIRIGRNECVVVIRVDKEKGYIDLSKRRV
SPEEAIKCEDKFTKSKTETLIDWCDEKELNLILTTGGTGFAPRDVTPEATKEVIEREAPGMALAMLMGSLNVTPLGMLSRPVCGIRGKTL
IINLPGSKKGSQECFQFILPALPHAIDLLRDAIVKVKEVHDELEDLPSPPPPLSPPPTTSPHKQTEDKGVQCEEEEEEKKDSGVASTEDS
SSSHITAAAIAAKKHPFYTSPAVVMAHGEQPIPGLINYSHHSTDERIPDSIISRGVQVLPRDTASLSTTPSESPRAQATSRLSTASCPTP
KVQSRCSSKENILRASHSAVDITKVARRHRMSPFPLTSMDKAFITVLEMTPVLGTEIINYRDGMGRVLAQDVYAKDNLPPFPASVKDGYA
VRAADGPGDRFIIGESQAGEQPTQTVMPGQVMRVTTGAPIPCGADAVVQVEDTELIRESDDGTEELEVRILVQARPGQDIRPIGHDIKRG
ECVLAKGTHMGPSEIGLLATVGVTEVEVNKFPVVAVMSTGNELLNPEDDLLPGKIRDSNRSTLLATIQEHGYPTINLGIVGDNPDDLLNA
LNEGISRADVIITSGGVSMGEKDYLKQVLDIDLHAQIHFGRVFMKPGLPTTFATLDIDGVRKIIFALPGNPVSAVVTCNLFVVPALRKMQ

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

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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/chr14:67827173/chr14:67576857)
- 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
EIF2S1 P05198	GPHN Q9NQX3
FUNCTION: Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:16289705). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (PubMed:16289705). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex (PubMed:16289705). In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (PubMed:16289705). EIF2S1/eIF-2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:19131336). {ECO:0000269\|PubMed:16289705, ECO:0000269\|PubMed:19131336}.	FUNCTION: Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Acts as a major instructive molecule at inhibitory synapses, where it also clusters GABA type A receptors (PubMed:25025157, PubMed:26613940). {ECO:0000250\|UniProtKB:Q03555, ECO:0000269\|PubMed:25025157, ECO:0000269\|PubMed:26613940}.; FUNCTION: Has also a catalytic activity and catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released. {ECO:0000269\|PubMed:26613940}.

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

EIF2S1

chr14:67841264

chr14:67291192

ENST00000256383

17_88

107.0

316.0

Domain

S1 motif

Hgene

EIF2S1

chr14:67841264

chr14:67291192

ENST00000466499

17_88

107.0

316.0

Domain

S1 motif

Tgene

GPHN

chr14:67841264

chr14:67291192

ENST00000315266

326_736

67.0

737.0

Region

Note=MPT adenylyltransferase

Tgene

GPHN

chr14:67841264

chr14:67291192

ENST00000478722

326_736

67.0

770.0

Region

Note=MPT adenylyltransferase

- 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

GPHN

chr14:67841264

chr14:67291192

ENST00000315266

14_166

67.0

737.0

Region

Note=MPT Mo-transferase

Tgene

GPHN

chr14:67841264

chr14:67291192

ENST00000478722

14_166

67.0

770.0

Region

Note=MPT Mo-transferase

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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
EIF2S1
GPHN

- 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 EIF2S1-GPHN

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 EIF2S1-GPHN

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
Tgene	GPHN	C1854990	Molybdenum Cofactor Deficiency, Complementation Group C	5	CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Tgene	GPHN	C0001956	Alcohol Use Disorder	1	CTD_human
Tgene	GPHN	C0001973	Alcoholic Intoxication, Chronic	1	CTD_human
Tgene	GPHN	C0009171	Cocaine Abuse	1	CTD_human
Tgene	GPHN	C0085762	Alcohol abuse	1	CTD_human
Tgene	GPHN	C0236736	Cocaine-Related Disorders	1	CTD_human
Tgene	GPHN	C0543888	Epileptic encephalopathy	1	GENOMICS_ENGLAND
Tgene	GPHN	C0600427	Cocaine Dependence	1	CTD_human