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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:HEBP1-NCK1

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: HEBP1-NCK1
	FusionPDB ID: 35999
	FusionGDB2.0 ID: 35999
		Hgene	Tgene
	Gene symbol	HEBP1	NCK1
	Gene ID	50865	4690
	Gene name	heme binding protein 1	NCK adaptor protein 1
	Synonyms	HBP\|HEBP	NCK\|NCKalpha\|nck-1
	Cytomap	12p13.1	3q22.3
	Type of gene	protein-coding	protein-coding
	Description	heme-binding protein 1p22HBP	cytoplasmic protein NCK1NCK tyrosine kinaseSH2/SH3 adaptor protein NCK-alphamelanoma NCK proteinnon-catalytic region of tyrosine kinase
	Modification date	20200313	20200327
	UniProtAcc	Q9NRV9	P16333
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000014930, ENST00000536942, ENST00000540916,	ENST00000469404, ENST00000288986, ENST00000481752,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	5 X 4 X 3=60	9 X 5 X 9=405
	# samples	6	12
	** MAII score	log2(6/60*10)=0	log2(12/405*10)=-1.75488750216347 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: HEBP1 [Title/Abstract] AND NCK1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	HEBP1(13140086)-NCK1(136667101), # samples:3 NCK1(136665137)-HEBP1(13128413), # samples:5
Anticipated loss of major functional domain due to fusion event.	NCK1-HEBP1 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. NCK1-HEBP1 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. HEBP1-NCK1 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. HEBP1-NCK1 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. HEBP1-NCK1 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. HEBP1-NCK1 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. HEBP1-NCK1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted 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	NCK1	GO:0033137	negative regulation of peptidyl-serine phosphorylation	14676213\|16835242
Tgene	NCK1	GO:0036493	positive regulation of translation in response to endoplasmic reticulum stress	14676213
Tgene	NCK1	GO:0045944	positive regulation of transcription by RNA polymerase II	10026169
Tgene	NCK1	GO:0060548	negative regulation of cell death	18835251
Tgene	NCK1	GO:0070262	peptidyl-serine dephosphorylation	16835242
Tgene	NCK1	GO:1902237	positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	14676213
Tgene	NCK1	GO:1903676	positive regulation of cap-dependent translational initiation	11959995
Tgene	NCK1	GO:1903679	positive regulation of cap-independent translational initiation	11959995
Tgene	NCK1	GO:1903898	negative regulation of PERK-mediated unfolded protein response	14676213
Tgene	NCK1	GO:1903912	negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation	14676213\|16835242
Tgene	NCK1	GO:1990441	negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress	16835242

Fusion gene breakpoints across HEBP1 (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 NCK1 (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-QK-A8ZB-01A	HEBP1	chr12	13140086	-	NCK1	chr3	136667101	+
ChimerDB4	HNSC	TCGA-QK-A8ZB	HEBP1	chr12	13140085	-	NCK1	chr3	136667100	+
ChimerDB4	HNSC	TCGA-QK-A8ZB	HEBP1	chr12	13140086	-	NCK1	chr3	136667101	+

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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)
ENST00000014930	HEBP1	chr12	13140086	-	ENST00000288986	NCK1	chr3	136667101	+	1425	557	33	581	182
ENST00000014930	HEBP1	chr12	13140086	-	ENST00000481752	NCK1	chr3	136667101	+	1425	557	33	581	182
ENST00000014930	HEBP1	chr12	13140085	-	ENST00000288986	NCK1	chr3	136667100	+	1425	557	33	581	182
ENST00000014930	HEBP1	chr12	13140085	-	ENST00000481752	NCK1	chr3	136667100	+	1425	557	33	581	182

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
ENST00000014930	ENST00000288986	HEBP1	chr12	13140086	-	NCK1	chr3	136667101	+	0.002615447	0.9973846
ENST00000014930	ENST00000481752	HEBP1	chr12	13140086	-	NCK1	chr3	136667101	+	0.002615447	0.9973846
ENST00000014930	ENST00000288986	HEBP1	chr12	13140085	-	NCK1	chr3	136667100	+	0.002615447	0.9973846
ENST00000014930	ENST00000481752	HEBP1	chr12	13140085	-	NCK1	chr3	136667100	+	0.002615447	0.9973846

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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

>35999_35999_1_HEBP1-NCK1_HEBP1_chr12_13140085_ENST00000014930_NCK1_chr3_136667100_ENST00000288986_length(amino acids)=182AA_BP=
MPPCRPAALPPCRPAAGGRCPWCSVAPATSRPPVRRERLGYNMLGMIKNSLFGSVETWPWQVLSKGDKEEVAYEERACEGGKFATVEVTD
KPVDEALREAMPKVAKYAGGTNDKGIGMGMTVPISFAVFPNEDGSLQKKLKVWFRIPNQFQSDPPAPSDKSVKIEEREGITVYSIQMISQ

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

>35999_35999_2_HEBP1-NCK1_HEBP1_chr12_13140085_ENST00000014930_NCK1_chr3_136667100_ENST00000481752_length(amino acids)=182AA_BP=
MPPCRPAALPPCRPAAGGRCPWCSVAPATSRPPVRRERLGYNMLGMIKNSLFGSVETWPWQVLSKGDKEEVAYEERACEGGKFATVEVTD
KPVDEALREAMPKVAKYAGGTNDKGIGMGMTVPISFAVFPNEDGSLQKKLKVWFRIPNQFQSDPPAPSDKSVKIEEREGITVYSIQMISQ

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

>35999_35999_3_HEBP1-NCK1_HEBP1_chr12_13140086_ENST00000014930_NCK1_chr3_136667101_ENST00000288986_length(amino acids)=182AA_BP=
MPPCRPAALPPCRPAAGGRCPWCSVAPATSRPPVRRERLGYNMLGMIKNSLFGSVETWPWQVLSKGDKEEVAYEERACEGGKFATVEVTD
KPVDEALREAMPKVAKYAGGTNDKGIGMGMTVPISFAVFPNEDGSLQKKLKVWFRIPNQFQSDPPAPSDKSVKIEEREGITVYSIQMISQ

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

>35999_35999_4_HEBP1-NCK1_HEBP1_chr12_13140086_ENST00000014930_NCK1_chr3_136667101_ENST00000481752_length(amino acids)=182AA_BP=
MPPCRPAALPPCRPAAGGRCPWCSVAPATSRPPVRRERLGYNMLGMIKNSLFGSVETWPWQVLSKGDKEEVAYEERACEGGKFATVEVTD
KPVDEALREAMPKVAKYAGGTNDKGIGMGMTVPISFAVFPNEDGSLQKKLKVWFRIPNQFQSDPPAPSDKSVKIEEREGITVYSIQMISQ

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

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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/chr12:13140086/chr3:136667101)
- 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
HEBP1 Q9NRV9	NCK1 P16333
FUNCTION: May bind free porphyrinogens that may be present in the cell and thus facilitate removal of these potentially toxic compound. Binds with a high affinity to one molecule of heme or porphyrins. It binds metalloporphyrins, free porphyrins and N-methylprotoporphyrin with similar affinities. {ECO:0000269\|PubMed:12413491}.	FUNCTION: Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA. May play a role in cell adhesion and migration through interaction with ephrin receptors. {ECO:0000269\|PubMed:10026169, ECO:0000269\|PubMed:16835242, ECO:0000269\|PubMed:17803907, ECO:0000269\|PubMed:18835251, ECO:0000269\|PubMed:23358419, ECO:0000269\|PubMed:9430661}.

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

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000469404

282_376

249.0

314.0

Domain

SH2

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000469404

282_376

249.0

314.0

Domain

SH2

- 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

NCK1

chr12:13140085

chr3:136667100

ENST00000288986

106_165

313.0

378.0

Domain

SH3 2

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000288986

190_252

313.0

378.0

Domain

SH3 3

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000288986

282_376

313.0

378.0

Domain

SH2

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000288986

2_61

313.0

378.0

Domain

SH3 1

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000469404

106_165

249.0

314.0

Domain

SH3 2

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000469404

190_252

249.0

314.0

Domain

SH3 3

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000469404

2_61

249.0

314.0

Domain

SH3 1

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000481752

106_165

313.0

378.0

Domain

SH3 2

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000481752

190_252

313.0

378.0

Domain

SH3 3

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000481752

282_376

313.0

378.0

Domain

SH2

Tgene

NCK1

chr12:13140085

chr3:136667100

ENST00000481752

2_61

313.0

378.0

Domain

SH3 1

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000288986

106_165

313.0

378.0

Domain

SH3 2

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000288986

190_252

313.0

378.0

Domain

SH3 3

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000288986

282_376

313.0

378.0

Domain

SH2

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000288986

2_61

313.0

378.0

Domain

SH3 1

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000469404

106_165

249.0

314.0

Domain

SH3 2

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000469404

190_252

249.0

314.0

Domain

SH3 3

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000469404

2_61

249.0

314.0

Domain

SH3 1

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000481752

106_165

313.0

378.0

Domain

SH3 2

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000481752

190_252

313.0

378.0

Domain

SH3 3

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000481752

282_376

313.0

378.0

Domain

SH2

Tgene

NCK1

chr12:13140086

chr3:136667101

ENST00000481752

2_61

313.0

378.0

Domain

SH3 1

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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)
PDB file >>>209_HEBP1_13140086_NCK1_136667101_ranked_0.pdb	HEBP1	13140085	13140086	ENST00000481752	NCK1	chr3	136667101	+	MPPCRPAALPPCRPAAGGRCPWCSVAPATSRPPVRRERLGYNMLGMIKNSLFGSVETWPWQVLSKGDKEEVAYEERACEGGKFATVEVTD KPVDEALREAMPKVAKYAGGTNDKGIGMGMTVPISFAVFPNEDGSLQKKLKVWFRIPNQFQSDPPAPSDKSVKIEEREGITVYSIQMISQ	182

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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.

HEBP1_pLDDT.png

NCK1_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
HEBP1
NCK1

- 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 HEBP1-NCK1

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 HEBP1-NCK1

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