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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:JAK2-GLDC

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: JAK2-GLDC
	FusionPDB ID: 40854
	FusionGDB2.0 ID: 40854
		Hgene	Tgene
	Gene symbol	JAK2	GLDC
	Gene ID	3717	2731
	Gene name	Janus kinase 2	glycine decarboxylase
	Synonyms	JTK10\|THCYT3	GCE\|GCSP\|HYGN1
	Cytomap	9p24.1	9p24.1
	Type of gene	protein-coding	protein-coding
	Description	tyrosine-protein kinase JAK2JAK-2Janus kinase 2 (a protein tyrosine kinase)	glycine dehydrogenase (decarboxylating), mitochondrialglycine cleavage system protein Pglycine decarboxylase P-proteinglycine dehydrogenase (aminomethyl-transferring)glycine dehydrogenase [decarboxylating], mitochondrialnonketotic hyperglycinemia
	Modification date	20200329	20200320
	UniProtAcc	O60674	P23378
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000381652, ENST00000539801, ENST00000487310, ENST00000544510,	ENST00000460457, ENST00000321612,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	13 X 10 X 8=1040	2 X 1 X 2=4
	# samples	11	3
	** MAII score	log2(11/1040*10)=-3.24100809950379 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(3/4*10)=2.90689059560852
Context (manual curation of fusion genes in FusionPDB)	PubMed: JAK2 [Title/Abstract] AND GLDC [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	JAK2(5029906)-GLDC(6565429), # samples:2
Anticipated loss of major functional domain due to fusion event.	JAK2-GLDC 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. JAK2-GLDC 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	JAK2	GO:0010811	positive regulation of cell-substrate adhesion	10925297
Hgene	JAK2	GO:0019221	cytokine-mediated signaling pathway	8609418
Hgene	JAK2	GO:0033209	tumor necrosis factor-mediated signaling pathway	8609418
Hgene	JAK2	GO:0034612	response to tumor necrosis factor	8609418
Hgene	JAK2	GO:0035409	histone H3-Y41 phosphorylation	19783980
Hgene	JAK2	GO:0035722	interleukin-12-mediated signaling pathway	7528775
Hgene	JAK2	GO:0046677	response to antibiotic	16280321
Hgene	JAK2	GO:0050727	regulation of inflammatory response	10925297
Hgene	JAK2	GO:0060396	growth hormone receptor signaling pathway	10925297
Hgene	JAK2	GO:0070671	response to interleukin-12	7528775
Tgene	GLDC	GO:0006546	glycine catabolic process	28244183

Fusion gene breakpoints across JAK2 (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 GLDC (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	HNSC	TCGA-HD-7229-01A	JAK2	chr9	5029906	-	GLDC	chr9	6565429	-
ChimerDB4	HNSC	TCGA-HD-7229-01A	JAK2	chr9	5029906	+	GLDC	chr9	6565429	-

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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)

ENST00000539801

JAK2

chr9

5029906

ENST00000321612

GLDC

chr9

6565429

2229

463

113

1675

520

ENST00000381652

JAK2

chr9

5029906

ENST00000321612

GLDC

chr9

6565429

2610

844

494

2056

520

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
ENST00000539801	ENST00000321612	JAK2	chr9	5029906	+	GLDC	chr9	6565429	-	0.000805238	0.9991948
ENST00000381652	ENST00000321612	JAK2	chr9	5029906	+	GLDC	chr9	6565429	-	0.001198609	0.99880135

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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

>40854_40854_1_JAK2-GLDC_JAK2_chr9_5029906_ENST00000381652_GLDC_chr9_6565429_ENST00000321612_length(amino acids)=520AA_BP=116
MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSE
TERIWYPPNHVFHIDESTRHNVLYRISGAQGEYAGLATIRAYLNQKGEGHRTVCLIPKSAHGTNPASAHMAGMKIQPVEVDKYGNIDAVH
LKAMVDKHKENLAAIMITYPSTNGVFEENISDVCDLIHQHGGQVYLDGANMNAQVGICRPGDFGSDVSHLNLHKTFCIPHGGGGPGMGPI
GVKKHLAPFLPNHPVISLKRNEDACPVGTVSAAPWGSSSILPISWAYIKMMGGKGLKQATETAILNANYMAKRLETHYRILFRGARGYVG
HEFILDTRPFKKSANIEAVDVAKRLQDYGFHAPTMSWPVAGTLMVEPTESEDKAELDRFCDAMISIRQEIADIEEGRIDPRVNPLKMSPH

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

>40854_40854_2_JAK2-GLDC_JAK2_chr9_5029906_ENST00000539801_GLDC_chr9_6565429_ENST00000321612_length(amino acids)=520AA_BP=116
MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSE
TERIWYPPNHVFHIDESTRHNVLYRISGAQGEYAGLATIRAYLNQKGEGHRTVCLIPKSAHGTNPASAHMAGMKIQPVEVDKYGNIDAVH
LKAMVDKHKENLAAIMITYPSTNGVFEENISDVCDLIHQHGGQVYLDGANMNAQVGICRPGDFGSDVSHLNLHKTFCIPHGGGGPGMGPI
GVKKHLAPFLPNHPVISLKRNEDACPVGTVSAAPWGSSSILPISWAYIKMMGGKGLKQATETAILNANYMAKRLETHYRILFRGARGYVG
HEFILDTRPFKKSANIEAVDVAKRLQDYGFHAPTMSWPVAGTLMVEPTESEDKAELDRFCDAMISIRQEIADIEEGRIDPRVNPLKMSPH

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

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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/chr9:5029906/chr9:6565429)
- 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
JAK2 O60674	GLDC P23378
FUNCTION: Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:7615558). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980). {ECO:0000269\|PubMed:12023369, ECO:0000269\|PubMed:19783980, ECO:0000269\|PubMed:20098430, ECO:0000269\|PubMed:21368206, ECO:0000269\|PubMed:21423214, ECO:0000269\|PubMed:7615558, ECO:0000269\|PubMed:9618263}.	FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein (GLDC) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (GCSH). {ECO:0000269\|PubMed:1993704, ECO:0000269\|PubMed:1996985, ECO:0000269\|PubMed:28244183}.

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

- 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

JAK2

chr9:5029906

chr9:6565429

ENST00000381652

37_380

116.66666666666667

1133.0

Domain

FERM

Hgene

JAK2

chr9:5029906

chr9:6565429

ENST00000381652

401_482

116.66666666666667

1133.0

Domain

SH2%3B atypical

Hgene

JAK2

chr9:5029906

chr9:6565429

ENST00000381652

545_809

116.66666666666667

1133.0

Domain

Protein kinase 1

Hgene

JAK2

chr9:5029906

chr9:6565429

ENST00000381652

849_1124

116.66666666666667

1133.0

Domain

Protein kinase 2

Hgene

JAK2

chr9:5029906

chr9:6565429

ENST00000539801

37_380

116.66666666666667

1133.0

Domain

FERM

Hgene

JAK2

chr9:5029906

chr9:6565429

ENST00000539801

401_482

116.66666666666667

1133.0

Domain

SH2%3B atypical

Hgene

JAK2

chr9:5029906

chr9:6565429

ENST00000539801

545_809

116.66666666666667

1133.0

Domain

Protein kinase 1

Hgene

JAK2

chr9:5029906

chr9:6565429

ENST00000539801

849_1124

116.66666666666667

1133.0

Domain

Protein kinase 2

Hgene

JAK2

chr9:5029906

chr9:6565429

ENST00000381652

855_863

116.66666666666667

1133.0

Nucleotide binding

ATP

Hgene

JAK2

chr9:5029906

chr9:6565429

ENST00000539801

855_863

116.66666666666667

1133.0

Nucleotide binding

ATP

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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

JAK2

PRMT5, SOCS1, PPIA, IL12RB2, EPOR, FYN, STAT5A, STAT5B, SH2B2, CXCR4, DNAJA3, HSPA8, TEC, PTPN12, PTK2, CSF2RB, GHR, VAV1, SIRPA, IRS1, BRCA1, GRB2, EGFR, PTK2B, PTPN11, TNFRSF1A, SOCS3, PTPN6, LYN, HTR2A, ERBB2, ELP2, KIT, RAF1, SH2B1, IL5RA, PPP2R1B, IFNGR1, IFNGR2, CCR5, PRLR, IL6ST, SHC1, GRB10, TUB, TSHR, STAT3, INSR, STAM, PTPN1, STAM2, IL2RB, CTLA4, ALK, IKBKG, FGFR1, STAT1, HSP90AA1, HSP90AB1, ASB2, SKP2, GTF2I, HIST3H3, HIST2H3C, CDKN1B, VHL, PIK3R1, MAP3K5, AGTR1, PTAFR, JAK2, IL4R, IL2RG, PPP1CC, ERBB3, CALM1, SRC, JAK3, PLCG1, HES1, HES5, Ifngr1, ASS1, RBMX, TRAF6, EZH2, DTX3L, EMD, KPNB1, NAP1L1, RCN1, SLC2A1, UBP1, ARL11, HSFY1, HDAC6, HNRNPL, CBL, RNF123, Lmo4, GOLPH3, IGF1R, PARP9, LNX1, LDOC1, CSK, MPL, CUL4A, CUL4B, M, JAK1, AMY1C, BPIFA2, ARHGAP18, BACH1, IGHA2, HMMR, MUC7, CST2, IGJ, PBK, MUC5B, SPRR3, ZG16B, VCP,

Protein-protein interactors based on sequence similarity (STRING)

Gene	STRING network
JAK2
GLDC

- 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
Hgene	JAK2	chr9:5029906	chr9:6565429	ENST00000381652	+	4	25	1_239	116.66666666666667	1133.0	cytokine/interferon/growth hormone receptors
Hgene	JAK2	chr9:5029906	chr9:6565429	ENST00000539801	+	3	24	1_239	116.66666666666667	1133.0	cytokine/interferon/growth hormone receptors

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Related Drugs to JAK2-GLDC

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 JAK2-GLDC

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
Hgene	JAK2	C0032463	Polycythemia Vera	12	CTD_human;ORPHANET;UNIPROT
Hgene	JAK2	C0040028	Thrombocythemia, Essential	10	CTD_human;ORPHANET
Hgene	JAK2	C0001815	Primary Myelofibrosis	9	CGI;CTD_human;GENOMICS_ENGLAND;ORPHANET
Hgene	JAK2	C3489628	Thrombocytosis, Autosomal Dominant	8	CTD_human
Hgene	JAK2	C0019154	Hepatic Vein Thrombosis	3	CTD_human;ORPHANET
Hgene	JAK2	C0856761	Budd-Chiari Syndrome	3	CTD_human;ORPHANET
Hgene	JAK2	C0009324	Ulcerative Colitis	2	CTD_human
Hgene	JAK2	C0027022	Myeloproliferative disease	2	CTD_human
Hgene	JAK2	C0151744	Myocardial Ischemia	2	CTD_human
Hgene	JAK2	C0836924	Thrombocytosis	2	CTD_human
Hgene	JAK2	C3281125	THROMBOCYTHEMIA 3	2	UNIPROT
Hgene	JAK2	C0000786	Spontaneous abortion	1	CTD_human
Hgene	JAK2	C0000822	Abortion, Tubal	1	CTD_human
Hgene	JAK2	C0006663	Calcinosis	1	CTD_human
Hgene	JAK2	C0007873	Uterine Cervical Neoplasm	1	CTD_human
Hgene	JAK2	C0018824	Heart valve disease	1	CTD_human
Hgene	JAK2	C0019207	Hepatoma, Morris	1	CTD_human
Hgene	JAK2	C0019208	Hepatoma, Novikoff	1	CTD_human
Hgene	JAK2	C0021368	Inflammation	1	CTD_human
Hgene	JAK2	C0023418	leukemia	1	CTD_human
Hgene	JAK2	C0023467	Leukemia, Myelocytic, Acute	1	CGI;CTD_human;UNIPROT
Hgene	JAK2	C0023893	Liver Cirrhosis, Experimental	1	CTD_human
Hgene	JAK2	C0023904	Liver Neoplasms, Experimental	1	CTD_human
Hgene	JAK2	C0025472	Mesenteric Vascular Occlusion	1	CTD_human
Hgene	JAK2	C0026998	Acute Myeloid Leukemia, M1	1	CTD_human
Hgene	JAK2	C0032461	Polycythemia	1	CTD_human
Hgene	JAK2	C0032962	Pregnancy Complications	1	CTD_human
Hgene	JAK2	C0033578	Prostatic Neoplasms	1	CTD_human
Hgene	JAK2	C0040038	Thromboembolism	1	CTD_human
Hgene	JAK2	C0042487	Venous Thrombosis	1	CTD_human
Hgene	JAK2	C0086404	Experimental Hepatoma	1	CTD_human
Hgene	JAK2	C0149871	Deep Vein Thrombosis	1	CTD_human
Hgene	JAK2	C0263628	Tumoral calcinosis	1	CTD_human
Hgene	JAK2	C0376358	Malignant neoplasm of prostate	1	CTD_human
Hgene	JAK2	C0400966	Non-alcoholic Fatty Liver Disease	1	CTD_human
Hgene	JAK2	C0521174	Microcalcification	1	CTD_human
Hgene	JAK2	C1527405	Erythrocytosis	1	CTD_human
Hgene	JAK2	C1879321	Acute Myeloid Leukemia (AML-M2)	1	CTD_human
Hgene	JAK2	C3241937	Nonalcoholic Steatohepatitis	1	CTD_human
Hgene	JAK2	C3495676	Anorectal Malformations	1	GENOMICS_ENGLAND
Hgene	JAK2	C3830362	Early Pregnancy Loss	1	CTD_human
Hgene	JAK2	C4048328	cervical cancer	1	CTD_human
Hgene	JAK2	C4303761	Familial thrombocytosis	1	ORPHANET
Hgene	JAK2	C4552766	Miscarriage	1	CTD_human