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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:XPR1_CDK6

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: XPR1_CDK6
	KinaseFusionDB ID: KFG7182
	FusionGDB2.0 ID: KFG7182
		Hgene	Tgene
	Gene symbol	XPR1	CDK6
	Gene ID	9213	1021
	Gene name	xenotropic and polytropic retrovirus receptor 1	cyclin dependent kinase 6
	Synonyms	IBGC6\|SLC53A1\|SYG1\|X3	MCPH12\|PLSTIRE
	Cytomap	1q25.3	7q21.2
	Type of gene	protein-coding	protein-coding
	Description	solute carrier family 53 member 1X-receptorphosphate exporter SLC53A1protein SYG1 homologsolute carrier family 53 (phosphate exporter), member 1xenotropic and polytropic murine leukemia virus receptor X3	cyclin-dependent kinase 6cell division protein kinase 6serine/threonine-protein kinase PLSTIRE
	Modification date	20240411	20240416
	UniProtAcc	Q9UBH6	Q00534
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000367589, ENST00000367590, ENST00000467345,	ENST00000265734, ENST00000424848, ENST00000491250,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: XPR1 [Title/Abstract] AND CDK6 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	XPR1(180850335)-CDK6(92272420), # samples:1

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	CDK6	GO:0000082	G1/S transition of mitotic cell cycle	8114739
Tgene	CDK6	GO:0001954	positive regulation of cell-matrix adhesion	10205165
Tgene	CDK6	GO:0003323	type B pancreatic cell development	20668294
Tgene	CDK6	GO:0006468	protein phosphorylation	8114739
Tgene	CDK6	GO:0010468	regulation of gene expression	15254224
Tgene	CDK6	GO:0045638	negative regulation of myeloid cell differentiation	17431401
Tgene	CDK6	GO:0045656	negative regulation of monocyte differentiation	26542173
Tgene	CDK6	GO:0045668	negative regulation of osteoblast differentiation	15254224
Tgene	CDK6	GO:0045786	negative regulation of cell cycle	14985467
Tgene	CDK6	GO:2000773	negative regulation of cellular senescence	17420273

Kinase Fusion gene breakpoints across XPR1 (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 CDK6 (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
ChiTaRS5.0	BI497397	XPR1	chr1	180850335	CDK6	chr7	92272420

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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/:180850335/:92272420)
- 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
XPR1 Q9UBH6	CDK6 Q00534
FUNCTION: Inorganic ion transporter that mediates phosphate ion export across plasma membrane. Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling. The molecular mechanism of phosphate transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated (PubMed:23791524, PubMed:25938945, PubMed:31043717) (By similarity). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), important intracellular signaling molecules involved in regulation of phosphate flux (PubMed:27080106). {ECO:0000250\|UniProtKB:Q9Z0U0, ECO:0000269\|PubMed:23791524, ECO:0000269\|PubMed:25938945, ECO:0000269\|PubMed:27080106, ECO:0000269\|PubMed:31043717}.	FUNCTION: Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269\|PubMed:12833137, ECO:0000269\|PubMed:14985467, ECO:0000269\|PubMed:15254224, ECO:0000269\|PubMed:15809340, ECO:0000269\|PubMed:17420273, ECO:0000269\|PubMed:17431401, ECO:0000269\|PubMed:20333249, ECO:0000269\|PubMed:20668294, ECO:0000269\|PubMed:23918663, ECO:0000269\|PubMed:8114739}.

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 XPR1_CDK6

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
CDK6	Q00534	human	RB1	P06400	S780	strPPtLsPIPHIPr	Rb_C
CDK6	Q00534	human	TFEB	P19484	S467	KASsRRssFsMEEGD	DUF3371
CDK6	Q00534	human	RBL2	Q08999	T401	SKALRIStPLtGVRY
CDK6	Q00534	human	TFEB	P19484	T331	RVHGLPttsPsGMNM	DUF3371
CDK6	Q00534	human	FOXM1	Q08050	T510	EDSSQsPtPRPKKSy
CDK6	Q00534	human	RUNX1	Q01196-8	S276	DTRQIQPsPPWSYDQ
CDK6	Q00534	human	RUNX1	Q01196-8	S48	TPPSTALsPGKMSEA
CDK6	Q00534	human	FOXM1	Q08050	T611	ETLPISstPSkSVLP
CDK6	Q00534	human	TSC2	P49815	S1452	LPSssPRsPsGLrPr
CDK6	Q00534	human	FOXM1	Q08050	S508	sWEDSSQsPtPRPKK
CDK6	Q00534	human	EGLN2	Q96KS0	S130	EDGGDAPsPsKRPWA
CDK6	Q00534	human	RUNX1	Q01196-8	T300	sPSVHPAtPIsPGRA
CDK6	Q00534	human	PKM	P14618-2	S37	MCRLDIDsPPITARN
CDK6	Q00534	human	FOXM1	Q08050	S522	KSySGLRsPtRCVSE
CDK6	Q00534	human	RB1	P06400	T826	LPtPtkMtPRsRILV	Rb_C
CDK6	Q00534	human	RUNX1	Q01196-8	S424	SMVGGERsPPRILPP	RunxI
CDK6	Q00534	human	RBL2	Q08999	S672	tLyDRySsPPAsTtR
CDK6	Q00534	human	RB1	P06400	S795	sPykFPssPLrIPGG	Rb_C
CDK6	Q00534	human	CELF1	Q92879	S302	TSSGSsPsSSSSNSV
CDK6	Q00534	human	RB1	P06400	T252	PINGsPRtPRRGQNR
CDK6	Q00534	human	PFKFB3	Q16875	S467	NsVtPLAsPEPtKKP
CDK6	Q00534	human	RB1	P06400	S788	PIPHIPrsPykFPss	Rb_C
CDK6	Q00534	human	FOXM1	Q08050	T627	tPEsWRLtPPAKVGG
CDK6	Q00534	human	RB1	P06400	S249	AVIPINGsPRtPRRG
CDK6	Q00534	human	PFKFB3	Q16875	T463	LMRRNsVtPLAsPEP
CDK6	Q00534	human	RBL2	Q08999	S1035	NMDAPPLsPyPFVRt
CDK6	Q00534	human	NPM1	P06748	T199	VkKsIrDtPAkNAQK
CDK6	Q00534	human	RB1	P06400	S612	MyLsPVRsPKKKGsT
CDK6	Q00534	human	FOXM1	Q08050	S704	IDVPKPGsPEPQVSG
CDK6	Q00534	human	TFEB	P19484	S142	AGNsAPNsPMAMLHI	MITF_TFEB_C_3_N
CDK6	Q00534	human	RUNX1	Q01196-8	S303	VHPAtPIsPGRASGM
CDK6	Q00534	human	CDKN1B	P46527	T187	NAGsVEQtPKKPGLR
CDK6	Q00534	human	PKM	P14618	S37	MCRLDIDsPPItARN
CDK6	Q00534	human	CDKN1A	P38936	S130	sGEQAEGsPGGPGDs
CDK6	Q00534	human	FOXM1	Q08050	S489	PPLEEWPsPAPSFkE
CDK6	Q00534	human	TFEB	P19484	S114	HIsPAQGsPkPPPAA	MITF_TFEB_C_3_N
CDK6	Q00534	human	TFE3	P19532	S246	PTGSAPNsPMALLTI	MITF_TFEB_C_3_N
CDK6	Q00534	human	FLNA	P21333	S2152	tRRRRAPsVANVGsH	Filamin
CDK6	Q00534	human	ELAVL1	Q15717	S202	LLsQLyHsPArrFGG
CDK6	Q00534	human	RB1	P06400	T821	kIsEGLPtPtkMtPR	Rb_C
CDK6	Q00534	human	RPRM	Q9NS64	S98	LVKDRRPsKEVEAVV
CDK6	Q00534	human	CDKN1B	P46527	S10	NVRVSNGsPsLErMD
CDK6	Q00534	human	FOXM1	Q08050	T600	EVGGPFKtPIkETLP
CDK6	Q00534	human	TP53	P04637	R249	CMGGMNRrPILTIIT	P53
CDK6	Q00534	human	RB1	P06400	S807	PGGNIyIsPLksPyk	Rb_C
CDK6	Q00534	human	FLNA	P21333	S1459	kCsGPGLsPGMVRAN	Filamin
CDK6	Q00534	human	FOXM1	Q08050	T620	SkSVLPRtPEsWRLt
CDK6	Q00534	human	RUNX1	Q01196-8	S293	QYLGSIAsPSVHPAt
CDK6	Q00534	human	TSC2	P49815	S1217	MSLENPLsPFSSDIN
CDK6	Q00534	human	RB1	P06400	S811	IyIsPLksPykIsEG	Rb_C
CDK6	Q00534	human	FOXM1	Q08050	S451	LLFGEGFsPLLPVQT

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
CDK6	ID	Description	0.00e+00
CDK6	GO:0030330	DNA damage respons	6.21e-09
CDK6	GO:0051169	nuclear transport	3.85e-06
CDK6	GO:2000134	negative regulation of G1/S transition of mitotic cell cycle	3.85e-06
CDK6	GO:1902807	negative regulation of cell cycle G1/S phase transition	5.10e-06
CDK6	GO:0051348	negative regulation of transferase activity	7.96e-06
CDK6	GO:0034504	protein localization to nucleus	4.18e-05
CDK6	GO:0006606	protein import into nucleus	4.18e-05
CDK6	GO:0010948	negative regulation of cell cycle process	4.18e-05
CDK6	GO:0051170	import into nucleus	4.18e-05
CDK6	GO:0072331	signal transduction by p53 class mediator	4.51e-05
CDK6	GO:0006469	negative regulation of protein kinase activity	4.51e-05
CDK6	GO:0006977	DNA damage respons	5.89e-07
CDK6	GO:0042772	DNA damage respons	6.99e-07
CDK6	GO:0033673	negative regulation of kinase activity	4.75e-05
CDK6	GO:1901991	negative regulation of mitotic cell cycle phase transition	4.75e-05
CDK6	GO:0045936	negative regulation of phosphate metabolic process	4.75e-05
CDK6	GO:0010563	negative regulation of phosphorus metabolic process	4.75e-05
CDK6	GO:1902806	regulation of cell cycle G1/S phase transition	5.93e-05
CDK6	GO:0045786	negative regulation of cell cycle	6.78e-05
CDK6	GO:0001558	regulation of cell growth	7.48e-05
CDK6	GO:0031571	mitotic G1 DNA damage checkpoint signaling	1.08e-04
CDK6	GO:0044819	mitotic G1/S transition checkpoint signaling	1.08e-04
CDK6	GO:1901987	regulation of cell cycle phase transition	1.08e-04
CDK6	GO:0045930	negative regulation of mitotic cell cycle	1.08e-04
CDK6	GO:0000082	G1/S transition of mitotic cell cycle	1.13e-04
CDK6	GO:0090398	cellular senescence	1.13e-04
CDK6	GO:0044772	mitotic cell cycle phase transition	1.16e-04
CDK6	GO:0043086	negative regulation of catalytic activity	1.27e-04
CDK6	GO:0016049	cell growth	1.50e-04
CDK6	GO:1901988	negative regulation of cell cycle phase transition	1.53e-04
CDK6	GO:0044843	cell cycle G1/S phase transition	1.54e-04
CDK6	GO:0001933	negative regulation of protein phosphorylation	2.27e-04
CDK6	GO:0042326	negative regulation of phosphorylation	3.14e-04
CDK6	GO:0044839	cell cycle G2/M phase transition	3.48e-04
CDK6	GO:1901990	regulation of mitotic cell cycle phase transition	4.44e-04
CDK6	GO:0009267	cellular response to starvation	5.82e-04
CDK6	GO:0030308	negative regulation of cell growth	7.03e-04
CDK6	GO:0031099	regeneration	7.15e-04
CDK6	GO:0031400	negative regulation of protein modification process	1.09e-03
CDK6	GO:0042594	response to starvation	1.13e-03
CDK6	GO:0042246	tissue regeneration	1.13e-03
CDK6	GO:0072594	establishment of protein localization to organelle	1.27e-03
CDK6	GO:0060965	negative regulation of miRNA-mediated gene silencing	1.27e-03
CDK6	GO:0071236	cellular response to antibiotic	1.27e-03
CDK6	GO:0044773	mitotic DNA damage checkpoint signaling	1.38e-03
CDK6	GO:0060149	negative regulation of post-transcriptional gene silencing	1.38e-03
CDK6	GO:0060967	negative regulation of gene silencing by regulatory ncRNA	1.38e-03
CDK6	GO:1900369	negative regulation of post-transcriptional gene silencing by regulatory ncRNA	1.38e-03
CDK6	GO:0044774	mitotic DNA integrity checkpoint signaling	1.49e-03

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Related Drugs to XPR1_CDK6

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 XPR1-CDK6 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 XPR1_CDK6

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	CDK6	C0004238	Atrial Fibrillation	2	CTD_human
Tgene	CDK6	C0025149	Medulloblastoma	2	CTD_human
Tgene	CDK6	C0205833	Medullomyoblastoma	2	CTD_human
Tgene	CDK6	C0235480	Paroxysmal atrial fibrillation	2	CTD_human
Tgene	CDK6	C0278510	Childhood Medulloblastoma	2	CTD_human
Tgene	CDK6	C0278876	Adult Medulloblastoma	2	CTD_human
Tgene	CDK6	C0751291	Desmoplastic Medulloblastoma	2	CTD_human
Tgene	CDK6	C1275668	Melanotic medulloblastoma	2	CTD_human
Tgene	CDK6	C2585653	Persistent atrial fibrillation	2	CTD_human
Tgene	CDK6	C3468561	familial atrial fibrillation	2	CTD_human

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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