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	Kinase Fusion Gene Summary
	Kinase Fusion Gene Sample Information
	Kinase Fusion ORF Analysis
	Kinase Fusion Amino Acid Sequences
	Multiple Sequence Alignment of All Fusion Protein Isoforms
	Kinase Fusion Protein Functional Features
	Kinase Fusion Protein Structures
	Comparison of Fusion Protein Isoforms
	Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB
	pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.
	Ramachandran Plot of Kinase Fusion Protein Structure
	Potential Active Site Information
	Virtual Screening Results
	Kinase-Substrate Information
	Related Drugs with This Kinase Fusion Protein
	Related Disease with This Kinase Fusion Protein
	Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:CDK12_JAK2

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: CDK12_JAK2
	KinaseFusionDB ID: KFG1060
	FusionGDB2.0 ID: KFG1060
		Hgene	Tgene
	Gene symbol	CDK12	JAK2
	Gene ID	51755	3717
	Gene name	cyclin dependent kinase 12	Janus kinase 2
	Synonyms	CRK7\|CRKR\|CRKRS	JTK10
	Cytomap	17q12	9p24.1
	Type of gene	protein-coding	protein-coding
	Description	cyclin-dependent kinase 12CDC2-related protein kinase 7Cdc2-related kinase, arginine/serine-richcell division cycle 2-related protein kinase 7cell division protein kinase 12	tyrosine-protein kinase JAK2JAK-2Janus kinase 2 (a protein tyrosine kinase)
	Modification date	20240403	20240411
	UniProtAcc	Q9NYV4	O60674
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000430627, ENST00000447079, ENST00000559545,	ENST00000487310, ENST00000381652, ENST00000539801, ENST00000544510,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: CDK12 [Title/Abstract] AND JAK2 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	CDK12(37628016)-JAK2(5126333), # samples:3

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	CDK12	GO:0006366	transcription by RNA polymerase II	22988298
Hgene	CDK12	GO:0032968	positive regulation of transcription elongation by RNA polymerase II	22988298
Hgene	CDK12	GO:0046777	protein autophosphorylation	11683387
Tgene	JAK2	GO:0007259	cell surface receptor signaling pathway via JAK-STAT	18692472\|31145836
Tgene	JAK2	GO:0010572	positive regulation of platelet activation	31145836
Tgene	JAK2	GO:0010811	positive regulation of cell-substrate adhesion	10925297
Tgene	JAK2	GO:0019221	cytokine-mediated signaling pathway	8609418
Tgene	JAK2	GO:0032729	positive regulation of type II interferon production	12023369\|19088061
Tgene	JAK2	GO:0032819	positive regulation of natural killer cell proliferation	19088061
Tgene	JAK2	GO:0033209	tumor necrosis factor-mediated signaling pathway	8609418
Tgene	JAK2	GO:0034612	response to tumor necrosis factor	8609418
Tgene	JAK2	GO:0035722	interleukin-12-mediated signaling pathway	7528775
Tgene	JAK2	GO:0038043	interleukin-5-mediated signaling pathway	7613138
Tgene	JAK2	GO:0038156	interleukin-3-mediated signaling pathway	8007942
Tgene	JAK2	GO:0038157	granulocyte-macrophage colony-stimulating factor signaling pathway	18692472
Tgene	JAK2	GO:0042102	positive regulation of T cell proliferation	11114383
Tgene	JAK2	GO:0043687	post-translational protein modification	19783980
Tgene	JAK2	GO:0046427	positive regulation of receptor signaling pathway via JAK-STAT	7638186\|12023369
Tgene	JAK2	GO:0046677	response to antibiotic	16280321
Tgene	JAK2	GO:0050727	regulation of inflammatory response	10925297
Tgene	JAK2	GO:0051142	positive regulation of NK T cell proliferation	19088061
Tgene	JAK2	GO:0060396	growth hormone receptor signaling pathway	10925297
Tgene	JAK2	GO:0070665	positive regulation of leukocyte proliferation	18692472
Tgene	JAK2	GO:0070671	response to interleukin-12	7528775
Tgene	JAK2	GO:1901731	positive regulation of platelet aggregation	31145836

Kinase Fusion gene breakpoints across CDK12 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Kinase Fusion gene breakpoints across JAK2 (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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Kinase Fusion Gene Sample Information

Kinase Fusion gene information.

Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE)
* 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	Sample	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp
ChimerDB4	TCGA-EW-A6S9-01A	CDK12	chr17	37628016	JAK2	chr9	5126333

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Kinase Fusion ORF Analysis

Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.

Henst

Tenst

Hgene

Hchr

Hbp

Tgene

Tchr

Tbp

Seq length
(transcript)

Seq length
(amino acids)

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Kinase Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq

Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase 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/:37628016/:5126333)
- 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
CDK12 Q9NYV4	JAK2 O60674
FUNCTION: Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269\|PubMed:11683387, ECO:0000269\|PubMed:19651820, ECO:0000269\|PubMed:20952539, ECO:0000269\|PubMed:22012619, ECO:0000269\|PubMed:24662513}.	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}.

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 domain in the 5'-partner of fusion protein (protein functional feature from UniProt).

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

- Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

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Kinase-Substrate Information of CDK12_JAK2

Phosphorylation target of the kinase
(phosphosite, 03-17-2024)

Kinase	Kinase UniProt Acc	Kinase species	Substrate	Substrate UniProt Acc	Substrate phosphorylated residues	Substrate phosphorylated sites (+/-7AA)	Domain
CDK12	Q9NYV4	human	PAK2	Q13177	T134	LkFyDsNtVkQKyLs
CDK12	Q9NYV4	human	POLR2A	P24928	S1616	TPQSPSysPtsPsYS	RNA_pol_Rpb1_R
CDK12	Q9NYV4	human	PAK2	Q13177	T169	TEAPAVVtEEEDDDE
CDK12	Q9NYV4	human	TP63	Q9H3D4-2	S68	TFDALsPsPAIPSNT
CDK12	Q9NYV4	human	POLR2A	P24928	S1619	SPSysPtsPsYSPTS	RNA_pol_Rpb1_R
CDK12	Q9NYV4	human	TP63	Q9H3D4-2	S66	SSTFDALsPsPAIPS
CDK12	Q9NYV4	human	TP63	Q9H3D4-2	S301	TSIKKRRsPDDELLY	P53_tetramer
JAK2	O60674	human	GTF2I	P78347-2	Y248	EESEDPDyyQyNIQG
JAK2	O60674	human	BECN1	Q14457	Y333	QRYRLVPyGNHsYLE	APG6
JAK2	O60674	human	PAK1	Q13153	Y285	QGASGTVyTAMDVAT	Pkinase
JAK2	O60674	human	PRMT5	O14744	Y307	FAKGyEDyLQsPLQP	PRMT5
JAK2	O60674	human	STAP2	Q9UGK3	Y250	PFLLDEDyEKVLGyV
JAK2	O60674	human	GRB2	P62993	Y209	TGMFPRNyVtPVNrN
JAK2	O60674	human	PRLR	P16471	S349	YLDPDTDsGRGSCDs
JAK2	O60674	human	EZH2	Q15910	Y641	kNEFISEyCGEIISQ	SET
JAK2	O60674	human	STAT5A	P42229	Y694	LAkAVDGyVkPQIkQ
JAK2	O60674	human	PPDPF	Q9H3Y8	Y17	LVATHDyyRRRLGst
JAK2	O60674	human	CCR2	P41597	Y139	ILLTIDRyLAIVHAV	7tm_1
JAK2	O60674	human	KDM3A	Q9Y4C1	Y1101	PDLGPKMyNAyGLIT
JAK2	O60674	human	BRD4	O60885	Y98	kLNLPDyykIIKtPM	Bromodomain
JAK2	O60674	human	JAK2	O60674	Y570	VRREVGDyGQLHETE	PK_Tyr_Ser-Thr
JAK2	O60674	human	PAK1	Q13153	Y153	tDksAEDyNssNALN
JAK2	O60674	human	GRB2	P62993	Y52	DGFIPkNyIEMkPHP
JAK2	O60674	human	SOCS3	O14543	Y221	IREFLDQyDAPL___
JAK2	O60674	human	STAT3	P40763	Y705	DPGsAAPyLktKFIC
JAK2	O60674	human	PRMT5	O14744	Y304	yELFAKGyEDyLQsP	PRMT5
JAK2	O60674	human	STAP2	Q9UGK3	Y22	GVLPSHYyESFLEKK	PH
JAK2	O60674	human	GAB2	Q9UQC2	Y643	tsDEKVDyVQVDKEK
JAK2	O60674	human	MAP3K5	Q99683	Y718	IPERDSRySQPLHEE	Pkinase
JAK2	O60674	human	ARHGEF1	Q92888	Y738	WDQEAQIyELVAQTV	PH_16
JAK2	O60674	human	H3C1	P68431	Y41	GVkkPHryrPGtVAL	Histone
JAK2	O60674	human	GRB2	P62993	Y37	EECDQNWykAELNGk	SH3_1
JAK2	O60674	human	GRB2	P62993	Y7	_MEAIAkyDFkATAD	SH3_1
JAK2	O60674	human	JAK2	O60674	S523	GVsDVPtsPTLQRPT
JAK2	O60674	human	PPDPF	Q9H3Y8	Y16	sLVATHDyyRRRLGs
JAK2	O60674	human	STAP2	Q9UGK3	Y322	GDGPAVDyENQDVAS
JAK2	O60674	human	TET2	Q6N021	Y1964	HETSEPTyLRFIKSL
JAK2	O60674	human	CHEK2	O96017	Y156	EVGPKNSyIAYIEDH	FHA
JAK2	O60674	human	PBK	Q96KB5	Y74	NPICNDHyRsVyQkR	Pkinase
JAK2	O60674	human	STAP2	Q9UGK3	Y310	LPNQEENyVTPIGDG
JAK2	O60674	human	PRMT5	O14744	Y297	NRPPPNAyELFAKGy	PRMT5
JAK2	O60674	human	MAPK1	P28482	Y187	HtGFLtEyVAtRWyr	Pkinase
JAK2	O60674	human	JAK2	O60674	Y119	VLYRIRFyFPRWYCS	FERM_F1
JAK2	O60674	human	PDHA1	P08559	Y301	MsDPGVsyRtREEIQ	E1_dh
JAK2	O60674	human	SOCS3	O14543	Y204	VNGHLDSyEkVTQLP
JAK2	O60674	human	PDK1	Q15118	Y243	ARRLCDLyyINSPEL
JAK2	O60674	human	BRD4	O60885	Y97	VkLNLPDyykIIKtP	Bromodomain
JAK2	O60674	human	MAPK3	P27361	Y204	HtGFLtEyVAtRWyr	Pkinase
JAK2	O60674	human	PAK1	Q13153	Y201	PEHtKsVyTRsVIEP
JAK2	O60674	human	TET2	Q6N021	Y1939	CEKYGPDyVPQKSHG
JAK2	O60674	human	STAT1	P42224	Y701	DGPkGtGyIktELIs

Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

Enriched GO biological processes of the phosphorylation target genes of the kinase

Kinase	GOID	GO term	P.adjust
CDK12	ID	Description	0.00e+00
CDK12	GO:2001235	positive regulation of apoptotic signaling pathway	2.92e-02
CDK12	GO:2001233	regulation of apoptotic signaling pathway	2.92e-02
CDK12	GO:0060525	prostate glandular acinus development	2.92e-02
CDK12	GO:2000271	positive regulation of fibroblast apoptotic process	2.92e-02
CDK12	GO:0060601	lateral sprouting from an epithelium	2.92e-02
CDK12	GO:0060742	epithelial cell differentiation involved in prostate gland development	2.92e-02
CDK12	GO:0035112	genitalia morphogenesis	2.92e-02
CDK12	GO:0043589	skin morphogenesis	2.92e-02
CDK12	GO:1904672	regulation of somatic stem cell population maintenance	2.92e-02
CDK12	GO:0034333	adherens junction assembly	2.92e-02
CDK12	GO:0045605	negative regulation of epidermal cell differentiation	2.92e-02
CDK12	GO:0045683	negative regulation of epidermis development	2.92e-02
CDK12	GO:0010838	positive regulation of keratinocyte proliferation	2.92e-02
CDK12	GO:0033147	negative regulation of intracellular estrogen receptor signaling pathway	2.92e-02
CDK12	GO:0060572	morphogenesis of an epithelial bud	2.92e-02
CDK12	GO:0030540	female genitalia development	2.92e-02
CDK12	GO:0036342	post-anal tail morphogenesis	2.92e-02
CDK12	GO:2000269	regulation of fibroblast apoptotic process	2.92e-02
CDK12	GO:0048485	sympathetic nervous system development	2.92e-02
CDK12	GO:0150105	protein localization to cell-cell junction	2.92e-02
CDK12	GO:1900118	negative regulation of execution phase of apoptosis	2.92e-02
CDK12	GO:0002223	stimulatory C-type lectin receptor signaling pathway	2.92e-02
CDK12	GO:1990840	response to lectin	2.92e-02
CDK12	GO:1990858	cellular response to lectin	2.92e-02
CDK12	GO:0060571	morphogenesis of an epithelial fold	2.92e-02
CDK12	GO:0030859	polarized epithelial cell differentiation	2.92e-02
CDK12	GO:0044346	fibroblast apoptotic process	2.92e-02
CDK12	GO:0060740	prostate gland epithelium morphogenesis	2.92e-02
CDK12	GO:0035116	embryonic hindlimb morphogenesis	2.92e-02
CDK12	GO:0060512	prostate gland morphogenesis	2.92e-02
CDK12	GO:0006353	DNA-templated transcription termination	2.92e-02
CDK12	GO:1900117	regulation of execution phase of apoptosis	2.92e-02
CDK12	GO:0031069	hair follicle morphogenesis	2.92e-02
CDK12	GO:0035115	embryonic forelimb morphogenesis	2.92e-02
CDK12	GO:0051497	negative regulation of stress fiber assembly	2.92e-02
CDK12	GO:0061436	establishment of skin barrier	2.92e-02
CDK12	GO:0009954	proximal/distal pattern formation	2.92e-02
CDK12	GO:0008340	determination of adult lifespan	2.92e-02
CDK12	GO:0033146	regulation of intracellular estrogen receptor signaling pathway	2.92e-02
CDK12	GO:0032232	negative regulation of actin filament bundle assembly	2.92e-02
CDK12	GO:0035137	hindlimb morphogenesis	2.92e-02
CDK12	GO:0033144	negative regulation of intracellular steroid hormone receptor signaling pathway	2.92e-02
CDK12	GO:0048730	epidermis morphogenesis	2.92e-02
CDK12	GO:0045616	regulation of keratinocyte differentiation	3.09e-02
CDK12	GO:0035136	forelimb morphogenesis	3.09e-02
CDK12	GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	3.14e-02
CDK12	GO:0033120	positive regulation of RNA splicing	3.14e-02
CDK12	GO:0048483	autonomic nervous system development	3.14e-02
CDK12	GO:0010837	regulation of keratinocyte proliferation	3.14e-02

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Related Drugs to CDK12_JAK2

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

Distribution of the number of studies mentioning CDK12-JAK2 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1

Fusion gene - drug pair 2

PMID

Publication date

DOI

Study title

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Related Diseases to CDK12_JAK2

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)

MeSH ID

MeSH term

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner	Gene	Disease ID	Disease name	# pubmeds	Source
Tgene	JAK2	C0032463	Polycythemia Vera	12	CTD_human;ORPHANET;UNIPROT
Tgene	JAK2	C0040028	Thrombocythemia, Essential	10	CTD_human;ORPHANET
Tgene	JAK2	C0001815	Primary Myelofibrosis	9	CGI;CTD_human;GENOMICS_ENGLAND;ORPHANET
Tgene	JAK2	C3489628	Thrombocytosis, Autosomal Dominant	8	CTD_human
Tgene	JAK2	C0019154	Hepatic Vein Thrombosis	3	CTD_human;ORPHANET
Tgene	JAK2	C0856761	Budd-Chiari Syndrome	3	CTD_human;ORPHANET
Tgene	JAK2	C0009324	Ulcerative Colitis	2	CTD_human
Tgene	JAK2	C0027022	Myeloproliferative disease	2	CTD_human
Tgene	JAK2	C0151744	Myocardial Ischemia	2	CTD_human
Tgene	JAK2	C0836924	Thrombocytosis	2	CTD_human
Tgene	JAK2	C3281125	THROMBOCYTHEMIA 3	2	UNIPROT

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Clinical Trials of the Found Drugs/Small Molecules

Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion Gene

Kinase Inhibitor

NCT ID

Study Status

Phases

Disease

# Enrolment

Date