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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein Structure
	pLDDT scores
	Ramachandran Plot of Fusion Protein Structure
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:STK39-NCKAP5

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: STK39-NCKAP5
	FusionPDB ID: 87558
	FusionGDB2.0 ID: 87558
		Hgene	Tgene
	Gene symbol	STK39	NCKAP5
	Gene ID	27347	344148
	Gene name	serine/threonine kinase 39	NCK associated protein 5
	Synonyms	DCHT\|PASK\|SPAK	ERIH1\|ERIH2\|NAP5
	Cytomap	2q24.3	2q21.2
	Type of gene	protein-coding	protein-coding
	Description	STE20/SPS1-related proline-alanine-rich protein kinaseSTE20/SPS1 homologSte20-like protein kinaseproline-alanine-rich STE20-related kinaseserine threonine kinase 39 (STE20/SPS1 homolog, yeast)serine/threonine-protein kinase 39small intestine SPAK-li	nck-associated protein 5NAP-5peripheral clock protein 2
	Modification date	20200313	20200313
	UniProtAcc	.	Q9HCH0
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000355999, ENST00000487143,	ENST00000473859, ENST00000317721, ENST00000405974, ENST00000409213, ENST00000409261,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	12 X 9 X 9=972	14 X 14 X 5=980
	# samples	12	15
	** MAII score	log2(12/972*10)=-3.01792190799726 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(15/980*10)=-2.70781924850669 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: STK39 [Title/Abstract] AND NCKAP5 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	STK39(168869144)-NCKAP5(133489624), # samples:3
Anticipated loss of major functional domain due to fusion event.	STK39-NCKAP5 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. STK39-NCKAP5 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. STK39-NCKAP5 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. STK39-NCKAP5 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	STK39	GO:0018105	peptidyl-serine phosphorylation	24393035
Hgene	STK39	GO:0018107	peptidyl-threonine phosphorylation	24393035
Hgene	STK39	GO:0023014	signal transduction by protein phosphorylation	24393035
Hgene	STK39	GO:0035556	intracellular signal transduction	24393035
Hgene	STK39	GO:1901017	negative regulation of potassium ion transmembrane transporter activity	24393035
Hgene	STK39	GO:1901380	negative regulation of potassium ion transmembrane transport	24393035
Hgene	STK39	GO:1905408	negative regulation of creatine transmembrane transporter activity	25531585
Hgene	STK39	GO:2000650	negative regulation of sodium ion transmembrane transporter activity	25531585

Fusion gene breakpoints across STK39 (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 NCKAP5 (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-CN-A49A-01A	STK39	chr2	168869144	-	NCKAP5	chr2	133489624	-
ChimerDB4	HNSC	TCGA-CN-A49A	STK39	chr2	168869144	-	NCKAP5	chr2	133489624	-

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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)
ENST00000355999	STK39	chr2	168869144	-	ENST00000409261	NCKAP5	chr2	133489624	-	4294	2204	454	2805	783
ENST00000355999	STK39	chr2	168869144	-	ENST00000409213	NCKAP5	chr2	133489624	-	3046	2204	454	2805	783
ENST00000355999	STK39	chr2	168869144	-	ENST00000405974	NCKAP5	chr2	133489624	-	2806	2204	454	2805	784
ENST00000355999	STK39	chr2	168869144	-	ENST00000317721	NCKAP5	chr2	133489624	-	2806	2204	454	2805	784

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
ENST00000355999	ENST00000409261	STK39	chr2	168869144	-	NCKAP5	chr2	133489624	-	0.00104677	0.9989532
ENST00000355999	ENST00000409213	STK39	chr2	168869144	-	NCKAP5	chr2	133489624	-	0.006737193	0.9932628
ENST00000355999	ENST00000405974	STK39	chr2	168869144	-	NCKAP5	chr2	133489624	-	0.008052921	0.9919471
ENST00000355999	ENST00000317721	STK39	chr2	168869144	-	NCKAP5	chr2	133489624	-	0.008052921	0.9919471

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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

>87558_87558_1_STK39-NCKAP5_STK39_chr2_168869144_ENST00000355999_NCKAP5_chr2_133489624_ENST00000317721_length(amino acids)=784AA_BP=583
MGARRAQRPPPPPFPASAGAASSLRPARPPLLPPLLAGFGGDGGGGGGRGGRAPAERCRRRGKGSFKWKVVRRPARPPALLRSIMAEPSG
SPVHVQLPQQAAPVTAAAAAAPAAATAAPAPAAPAAPAPAPAPAAQAVGWPICRDAYELQEVIGSGATAVVQAALCKPRQERVAIKRINL
EKCQTSMDELLKEIQAMSQCSHPNVVTYYTSFVVKDELWLVMKLLSGGSMLDIIKYIVNRGEHKNGVLEEAIIATILKEVLEGLDYLHRN
GQIHRDLKAGNILLGEDGSVQIADFGVSAFLATGGDVTRNKVRKTFVGTPCWMAPEVMEQVRGYDFKADMWSFGITAIELATGAAPYHKY
PPMKVLMLTLQNDPPTLETGVEDKEMMKKYGKSFRKLLSLCLQKDPSKRPTAAELLKCKFFQKAKNREYLIEKLLTRTPDIAQRAKKVRR
VPGSSGHLHKTEDGDWEWSDDEMDEKSEEGKAAFSQEKSRRVKEENPEIAVSASTIPEQIQSLSVHDSQGPPNANEDYREASSCAVNLVL
RLRNSRKELNDIRFEFTPGRDTADGVSQELFSAGLVDGHDVVIESNCQMRTLDSGIGTFPLPDSGNRSTGRYLCQPDSPEDAEPLLPLQS
ALSAVSSMRAQTLEREVPSSTDGQRPADSAIVHSTSDPIMTARGMRPLQSRLPKPASSGKVSSQKQNEAEPRPQTCSSFGYAEDPMASQP

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

>87558_87558_2_STK39-NCKAP5_STK39_chr2_168869144_ENST00000355999_NCKAP5_chr2_133489624_ENST00000405974_length(amino acids)=784AA_BP=583
MGARRAQRPPPPPFPASAGAASSLRPARPPLLPPLLAGFGGDGGGGGGRGGRAPAERCRRRGKGSFKWKVVRRPARPPALLRSIMAEPSG
SPVHVQLPQQAAPVTAAAAAAPAAATAAPAPAAPAAPAPAPAPAAQAVGWPICRDAYELQEVIGSGATAVVQAALCKPRQERVAIKRINL
EKCQTSMDELLKEIQAMSQCSHPNVVTYYTSFVVKDELWLVMKLLSGGSMLDIIKYIVNRGEHKNGVLEEAIIATILKEVLEGLDYLHRN
GQIHRDLKAGNILLGEDGSVQIADFGVSAFLATGGDVTRNKVRKTFVGTPCWMAPEVMEQVRGYDFKADMWSFGITAIELATGAAPYHKY
PPMKVLMLTLQNDPPTLETGVEDKEMMKKYGKSFRKLLSLCLQKDPSKRPTAAELLKCKFFQKAKNREYLIEKLLTRTPDIAQRAKKVRR
VPGSSGHLHKTEDGDWEWSDDEMDEKSEEGKAAFSQEKSRRVKEENPEIAVSASTIPEQIQSLSVHDSQGPPNANEDYREASSCAVNLVL
RLRNSRKELNDIRFEFTPGRDTADGVSQELFSAGLVDGHDVVIESNCQMRTLDSGIGTFPLPDSGNRSTGRYLCQPDSPEDAEPLLPLQS
ALSAVSSMRAQTLEREVPSSTDGQRPADSAIVHSTSDPIMTARGMRPLQSRLPKPASSGKVSSQKQNEAEPRPQTCSSFGYAEDPMASQP

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

>87558_87558_3_STK39-NCKAP5_STK39_chr2_168869144_ENST00000355999_NCKAP5_chr2_133489624_ENST00000409213_length(amino acids)=783AA_BP=583
MGARRAQRPPPPPFPASAGAASSLRPARPPLLPPLLAGFGGDGGGGGGRGGRAPAERCRRRGKGSFKWKVVRRPARPPALLRSIMAEPSG
SPVHVQLPQQAAPVTAAAAAAPAAATAAPAPAAPAAPAPAPAPAAQAVGWPICRDAYELQEVIGSGATAVVQAALCKPRQERVAIKRINL
EKCQTSMDELLKEIQAMSQCSHPNVVTYYTSFVVKDELWLVMKLLSGGSMLDIIKYIVNRGEHKNGVLEEAIIATILKEVLEGLDYLHRN
GQIHRDLKAGNILLGEDGSVQIADFGVSAFLATGGDVTRNKVRKTFVGTPCWMAPEVMEQVRGYDFKADMWSFGITAIELATGAAPYHKY
PPMKVLMLTLQNDPPTLETGVEDKEMMKKYGKSFRKLLSLCLQKDPSKRPTAAELLKCKFFQKAKNREYLIEKLLTRTPDIAQRAKKVRR
VPGSSGHLHKTEDGDWEWSDDEMDEKSEEGKAAFSQEKSRRVKEENPEIAVSASTIPEQIQSLSVHDSQGPPNANEDYREASSCAVNLVL
RLRNSRKELNDIRFEFTPGRDTADGVSQELFSAGLVDGHDVVIESNCQMRTLDSGIGTFPLPDSGNRSTGRYLCQPDSPEDAEPLLPLQS
ALSAVSSMRAQTLEREVPSSTDGQRPADSAIVHSTSDPIMTARGMRPLQSRLPKPASSGKVSSQKQNEAEPRPQTCSSFGYAEDPMASQP

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

>87558_87558_4_STK39-NCKAP5_STK39_chr2_168869144_ENST00000355999_NCKAP5_chr2_133489624_ENST00000409261_length(amino acids)=783AA_BP=583
MGARRAQRPPPPPFPASAGAASSLRPARPPLLPPLLAGFGGDGGGGGGRGGRAPAERCRRRGKGSFKWKVVRRPARPPALLRSIMAEPSG
SPVHVQLPQQAAPVTAAAAAAPAAATAAPAPAAPAAPAPAPAPAAQAVGWPICRDAYELQEVIGSGATAVVQAALCKPRQERVAIKRINL
EKCQTSMDELLKEIQAMSQCSHPNVVTYYTSFVVKDELWLVMKLLSGGSMLDIIKYIVNRGEHKNGVLEEAIIATILKEVLEGLDYLHRN
GQIHRDLKAGNILLGEDGSVQIADFGVSAFLATGGDVTRNKVRKTFVGTPCWMAPEVMEQVRGYDFKADMWSFGITAIELATGAAPYHKY
PPMKVLMLTLQNDPPTLETGVEDKEMMKKYGKSFRKLLSLCLQKDPSKRPTAAELLKCKFFQKAKNREYLIEKLLTRTPDIAQRAKKVRR
VPGSSGHLHKTEDGDWEWSDDEMDEKSEEGKAAFSQEKSRRVKEENPEIAVSASTIPEQIQSLSVHDSQGPPNANEDYREASSCAVNLVL
RLRNSRKELNDIRFEFTPGRDTADGVSQELFSAGLVDGHDVVIESNCQMRTLDSGIGTFPLPDSGNRSTGRYLCQPDSPEDAEPLLPLQS
ALSAVSSMRAQTLEREVPSSTDGQRPADSAIVHSTSDPIMTARGMRPLQSRLPKPASSGKVSSQKQNEAEPRPQTCSSFGYAEDPMASQP

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

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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/chr2:168869144/chr2:133489624)
- 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
.	NCKAP5 Q9HCH0
FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.	FUNCTION: Regulates microtubule organization and stabilization. Promotes microtubule growth and bundling formation and stabilizes microtubules by increasing intense acetylation of microtubules (PubMed:26482847, PubMed:26485573). Both tubulin-binding and homodimer formation are required for NCKAP5L-mediated microtubule bundle formation (PubMed:26485573). {ECO:0000269\|PubMed:26482847, ECO:0000269\|PubMed:26485573}.

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

STK39

chr2:168869144

chr2:133489624

ENST00000355999

12_53

499.3333333333333

546.0

Compositional bias

Note=Ala/Pro-rich

Hgene

STK39

chr2:168869144

chr2:133489624

ENST00000355999

63_337

499.3333333333333

546.0

Domain

Protein kinase

Hgene

STK39

chr2:168869144

chr2:133489624

ENST00000355999

360_366

499.3333333333333

546.0

Motif

Nuclear localization signal

Hgene

STK39

chr2:168869144

chr2:133489624

ENST00000355999

387_391

499.3333333333333

546.0

Motif

Note=Caspase cleavage related site

Hgene

STK39

chr2:168869144

chr2:133489624

ENST00000355999

69_77

499.3333333333333

546.0

Nucleotide binding

ATP

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000405974

1080_1130

390.3333333333333

591.0

Compositional bias

Note=Ser-rich

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000405974

927_933

390.3333333333333

591.0

Compositional bias

Note=Poly-Pro

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000409213

1080_1130

390.3333333333333

591.0

Compositional bias

Note=Ser-rich

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000409213

927_933

390.3333333333333

591.0

Compositional bias

Note=Poly-Pro

- 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

NCKAP5

chr2:168869144

chr2:133489624

ENST00000317721

71_253

1709.3333333333333

1910.0

Coiled coil

Ontology_term=ECO:0000255

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000405974

71_253

390.3333333333333

591.0

Coiled coil

Ontology_term=ECO:0000255

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000409213

71_253

390.3333333333333

591.0

Coiled coil

Ontology_term=ECO:0000255

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000409261

71_253

1709.3333333333333

1910.0

Coiled coil

Ontology_term=ECO:0000255

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000317721

1080_1130

1709.3333333333333

1910.0

Compositional bias

Note=Ser-rich

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000317721

331_386

1709.3333333333333

1910.0

Compositional bias

Note=Ser-rich

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000317721

927_933

1709.3333333333333

1910.0

Compositional bias

Note=Poly-Pro

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000405974

331_386

390.3333333333333

591.0

Compositional bias

Note=Ser-rich

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000409213

331_386

390.3333333333333

591.0

Compositional bias

Note=Ser-rich

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000409261

1080_1130

1709.3333333333333

1910.0

Compositional bias

Note=Ser-rich

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000409261

331_386

1709.3333333333333

1910.0

Compositional bias

Note=Ser-rich

Tgene

NCKAP5

chr2:168869144

chr2:133489624

ENST00000409261

927_933

1709.3333333333333

1910.0

Compositional bias

Note=Poly-Pro

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Fusion Protein Structures

PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

Fusion protein PDB link (fusion AA seq ID in FusionPDB)

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

AA seq

Len(AA seq)

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pLDDT score distribution

pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

STK39_pLDDT.png

NCKAP5_pLDDT.png

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

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Ramachandran Plot of Fusion Protein Structure

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

Fusion AA seq ID in FusionPDB and their Ramachandran plots

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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
STK39
NCKAP5

- 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	STK39	chr2:168869144	chr2:133489624	ENST00000355999	-	16	18	310_536	499.3333333333333	546.0	RELT

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Related Drugs to STK39-NCKAP5

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 STK39-NCKAP5

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