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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:NUDC-MICU1

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: NUDC-MICU1
	FusionPDB ID: 60817
	FusionGDB2.0 ID: 60817
		Hgene	Tgene
	Gene symbol	NUDC	MICU1
	Gene ID	10726	10367
	Gene name	nuclear distribution C, dynein complex regulator	mitochondrial calcium uptake 1
	Synonyms	HNUDC\|MNUDC\|NPD011	CALC\|CBARA1\|EFHA3\|MPXPS\|ara CALC
	Cytomap	1p36.11	10q22.1
	Type of gene	protein-coding	protein-coding
	Description	nuclear migration protein nudCnuclear distribution C homolognuclear distribution gene C homolognuclear distribution protein C homolognudC nuclear distribution protein	calcium uptake protein 1, mitochondrialatopy-related autoantigen CALCcalcium-binding atopy-related autoantigen 1
	Modification date	20200313	20200313
	UniProtAcc	NUDCD3	Q9BPX6
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000321265, ENST00000484772,	ENST00000604025, ENST00000361114, ENST00000398761, ENST00000398763, ENST00000401998, ENST00000418483,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	6 X 4 X 4=96	22 X 15 X 11=3630
	# samples	6	30
	** MAII score	log2(6/96*10)=-0.678071905112638 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(30/3630*10)=-3.59693514238723 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: NUDC [Title/Abstract] AND MICU1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	NUDC(27250657)-MICU1(74183129), # samples:2
Anticipated loss of major functional domain due to fusion event.	NUDC-MICU1 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. NUDC-MICU1 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. NUDC-MICU1 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. NUDC-MICU1 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
Tgene	MICU1	GO:0006851	mitochondrial calcium ion transmembrane transport	24560927
Tgene	MICU1	GO:0051260	protein homooligomerization	24514027
Tgene	MICU1	GO:0051561	positive regulation of mitochondrial calcium ion concentration	24560927
Tgene	MICU1	GO:0070509	calcium ion import	20693986

Fusion gene breakpoints across NUDC (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 MICU1 (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	COAD	TCGA-AA-3858-01A	NUDC	chr1	27250657	+	MICU1	chr10	74183129	-
ChimerDB4	COAD	TCGA-AA-3858	NUDC	chr1	27250657	+	MICU1	chr10	74183129	-

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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)
ENST00000321265	NUDC	chr1	27250657	+	ENST00000401998	MICU1	chr10	74183129	-	1635	282	123	779	218
ENST00000321265	NUDC	chr1	27250657	+	ENST00000361114	MICU1	chr10	74183129	-	1635	282	123	779	218
ENST00000321265	NUDC	chr1	27250657	+	ENST00000398761	MICU1	chr10	74183129	-	1635	282	123	779	218
ENST00000321265	NUDC	chr1	27250657	+	ENST00000418483	MICU1	chr10	74183129	-	1061	282	123	779	218
ENST00000321265	NUDC	chr1	27250657	+	ENST00000398763	MICU1	chr10	74183129	-	864	282	123	779	218

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
ENST00000321265	ENST00000401998	NUDC	chr1	27250657	+	MICU1	chr10	74183129	-	0.002948614	0.99705136
ENST00000321265	ENST00000361114	NUDC	chr1	27250657	+	MICU1	chr10	74183129	-	0.002948614	0.99705136
ENST00000321265	ENST00000398761	NUDC	chr1	27250657	+	MICU1	chr10	74183129	-	0.002948614	0.99705136
ENST00000321265	ENST00000418483	NUDC	chr1	27250657	+	MICU1	chr10	74183129	-	0.003998407	0.99600154
ENST00000321265	ENST00000398763	NUDC	chr1	27250657	+	MICU1	chr10	74183129	-	0.004218409	0.99578166

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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

>60817_60817_1_NUDC-MICU1_NUDC_chr1_27250657_ENST00000321265_MICU1_chr10_74183129_ENST00000361114_length(amino acids)=218AA_BP=53
MGGEQEEERFDGMLLAMAQQHEGGVQELVNTFFSFLRRKTDFFIGGEEGMAEKFERHDPVDGRITERQFGGMLLAYSGVQSKKLTAMQRQ
LKKHFKEGKGLTFQEVENFFTFLKNINDVDTALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVSIMK

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

>60817_60817_2_NUDC-MICU1_NUDC_chr1_27250657_ENST00000321265_MICU1_chr10_74183129_ENST00000398761_length(amino acids)=218AA_BP=53
MGGEQEEERFDGMLLAMAQQHEGGVQELVNTFFSFLRRKTDFFIGGEEGMAEKFERHDPVDGRITERQFGGMLLAYSGVQSKKLTAMQRQ
LKKHFKEGKGLTFQEVENFFTFLKNINDVDTALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVSIMK

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

>60817_60817_3_NUDC-MICU1_NUDC_chr1_27250657_ENST00000321265_MICU1_chr10_74183129_ENST00000398763_length(amino acids)=218AA_BP=53
MGGEQEEERFDGMLLAMAQQHEGGVQELVNTFFSFLRRKTDFFIGGEEGMAEKFERHDPVDGRITERQFGGMLLAYSGVQSKKLTAMQRQ
LKKHFKEGKGLTFQEVENFFTFLKNINDVDTALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVSIMK

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

>60817_60817_4_NUDC-MICU1_NUDC_chr1_27250657_ENST00000321265_MICU1_chr10_74183129_ENST00000401998_length(amino acids)=218AA_BP=53
MGGEQEEERFDGMLLAMAQQHEGGVQELVNTFFSFLRRKTDFFIGGEEGMAEKFERHDPVDGRITERQFGGMLLAYSGVQSKKLTAMQRQ
LKKHFKEGKGLTFQEVENFFTFLKNINDVDTALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVSIMK

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

>60817_60817_5_NUDC-MICU1_NUDC_chr1_27250657_ENST00000321265_MICU1_chr10_74183129_ENST00000418483_length(amino acids)=218AA_BP=53
MGGEQEEERFDGMLLAMAQQHEGGVQELVNTFFSFLRRKTDFFIGGEEGMAEKFERHDPVDGRITERQFGGMLLAYSGVQSKKLTAMQRQ
LKKHFKEGKGLTFQEVENFFTFLKNINDVDTALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVSIMK

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

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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/chr1:27250657/chr10:74183129)
- 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
NUDC NUDCD3	MICU1 Q9BPX6
361	FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU) that senses calcium level via its EF-hand domains (PubMed:20693986, PubMed:23101630, PubMed:23747253, PubMed:24313810, PubMed:24332854, PubMed:24503055, PubMed:24560927, PubMed:26341627, PubMed:26903221, PubMed:27099988). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium. MICU1 acts both as an activator or inhibitor of mitochondrial calcium uptake (PubMed:26903221). Acts as a gatekeeper of MCU at low concentration of calcium, preventing channel opening (PubMed:26903221). Enhances MCU opening at high calcium concentration, allowing a rapid response of mitochondria to calcium signals generated in the cytoplasm (PubMed:24560927, PubMed:26903221). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (PubMed:16002733). {ECO:0000269\|PubMed:16002733, ECO:0000269\|PubMed:20693986, ECO:0000269\|PubMed:22904319, ECO:0000269\|PubMed:23101630, ECO:0000269\|PubMed:23747253, ECO:0000269\|PubMed:24313810, ECO:0000269\|PubMed:24332854, ECO:0000269\|PubMed:24503055, ECO:0000269\|PubMed:24560927, ECO:0000269\|PubMed:26341627, ECO:0000269\|PubMed:26903221, ECO:0000269\|PubMed:27099988}.

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

MICU1

chr1:27250657

chr10:74183129

ENST00000361114

421_432

311.0

477.0

Calcium binding

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000398763

231_242

113.0

279.0

Calcium binding

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000398763

421_432

113.0

279.0

Calcium binding

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000418483

231_242

113.0

279.0

Calcium binding

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000418483

421_432

113.0

279.0

Calcium binding

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000361114

408_443

311.0

477.0

Domain

EF-hand 2

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000398763

218_253

113.0

279.0

Domain

EF-hand 1

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000398763

408_443

113.0

279.0

Domain

EF-hand 2

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000418483

218_253

113.0

279.0

Domain

EF-hand 1

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000418483

408_443

113.0

279.0

Domain

EF-hand 2

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000361114

455_465

311.0

477.0

Region

C-helix region

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000398763

455_465

113.0

279.0

Region

C-helix region

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000418483

455_465

113.0

279.0

Region

C-helix region

- 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

NUDC

chr1:27250657

chr10:74183129

ENST00000321265

60_134

53.0

332.0

Coiled coil

Ontology_term=ECO:0000255

Hgene

NUDC

chr1:27250657

chr10:74183129

ENST00000321265

167_258

53.0

332.0

Domain

Hgene

NUDC

chr1:27250657

chr10:74183129

ENST00000321265

68_74

53.0

332.0

Motif

Nuclear localization signal

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000361114

231_242

311.0

477.0

Calcium binding

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000361114

218_253

311.0

477.0

Domain

EF-hand 1

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000361114

99_110

311.0

477.0

Region

Polybasic region

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000398763

99_110

113.0

279.0

Region

Polybasic region

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000418483

99_110

113.0

279.0

Region

Polybasic region

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000361114

53_476

311.0

477.0

Topological domain

Mitochondrial intermembrane

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000398763

53_476

113.0

279.0

Topological domain

Mitochondrial intermembrane

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000418483

53_476

113.0

279.0

Topological domain

Mitochondrial intermembrane

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000361114

34_52

311.0

477.0

Transmembrane

Helical

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000398763

34_52

113.0

279.0

Transmembrane

Helical

Tgene

MICU1

chr1:27250657

chr10:74183129

ENST00000418483

34_52

113.0

279.0

Transmembrane

Helical

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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 >>>322_NUDC_27250657_MICU1_74183129_ranked_0.pdb	NUDC	27250657	27250657	ENST00000398763	MICU1	chr10	74183129	-	MGGEQEEERFDGMLLAMAQQHEGGVQELVNTFFSFLRRKTDFFIGGEEGMAEKFERHDPVDGRITERQFGGMLLAYSGVQSKKLTAMQRQ LKKHFKEGKGLTFQEVENFFTFLKNINDVDTALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVSIMK	218

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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.

NUDC_pLDDT.png

MICU1_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
NUDC
MICU1

- 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	NUDC	chr1:27250657	chr10:74183129	ENST00000321265	+	2	9	173_331	53.0	332.0	EML4

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Related Drugs to NUDC-MICU1

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 NUDC-MICU1

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