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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:MICU1-NRG3 (FusionGDB2 ID:53573)

Fusion Gene Summary for MICU1-NRG3

check button Fusion gene summary
Fusion gene informationFusion gene name: MICU1-NRG3
Fusion gene ID: 53573
HgeneTgene
Gene symbol

MICU1

NRG3

Gene ID

10367

10718

Gene namemitochondrial calcium uptake 1neuregulin 3
SynonymsCALC|CBARA1|EFHA3|MPXPS|ara CALCHRG3|pro-NRG3
Cytomap

10q22.1

10q23.1

Type of geneprotein-codingprotein-coding
Descriptioncalcium uptake protein 1, mitochondrialatopy-related autoantigen CALCcalcium-binding atopy-related autoantigen 1pro-neuregulin-3, membrane-bound isoformneuregulin-3-like polypeptide
Modification date2020031320200313
UniProtAcc

Q9BPX6

P56975

Ensembl transtripts involved in fusion geneENST00000361114, ENST00000398761, 
ENST00000398763, ENST00000401998, 
ENST00000418483, ENST00000604025, 
ENST00000537893, ENST00000545131, 
ENST00000372141, ENST00000372142, 
ENST00000404547, ENST00000404576, 
ENST00000556918, 
Fusion gene scores* DoF score13 X 11 X 8=114416 X 15 X 5=1200
# samples 1716
** MAII scorelog2(17/1144*10)=-2.75048040064069
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(16/1200*10)=-2.90689059560852
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: MICU1 [Title/Abstract] AND NRG3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointMICU1(74234858)-NRG3(84118495), # samples:1
Anticipated loss of major functional domain due to fusion event.MICU1-NRG3 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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneMICU1

GO:0006851

mitochondrial calcium ion transmembrane transport

24560927

HgeneMICU1

GO:0051260

protein homooligomerization

24514027

HgeneMICU1

GO:0051561

positive regulation of mitochondrial calcium ion concentration

24560927

HgeneMICU1

GO:0070509

calcium ion import

20693986


check buttonFusion gene breakpoints across MICU1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across NRG3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check button 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4BLCATCGA-FD-A3B6-01AMICU1chr10

74234858

-NRG3chr10

84118495

+


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Fusion Gene ORF analysis for MICU1-NRG3

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5CDS-intronENST00000361114ENST00000537893MICU1chr10

74234858

-NRG3chr10

84118495

+
5CDS-intronENST00000361114ENST00000545131MICU1chr10

74234858

-NRG3chr10

84118495

+
5CDS-intronENST00000398761ENST00000537893MICU1chr10

74234858

-NRG3chr10

84118495

+
5CDS-intronENST00000398761ENST00000545131MICU1chr10

74234858

-NRG3chr10

84118495

+
5CDS-intronENST00000398763ENST00000537893MICU1chr10

74234858

-NRG3chr10

84118495

+
5CDS-intronENST00000398763ENST00000545131MICU1chr10

74234858

-NRG3chr10

84118495

+
5CDS-intronENST00000401998ENST00000537893MICU1chr10

74234858

-NRG3chr10

84118495

+
5CDS-intronENST00000401998ENST00000545131MICU1chr10

74234858

-NRG3chr10

84118495

+
5CDS-intronENST00000418483ENST00000537893MICU1chr10

74234858

-NRG3chr10

84118495

+
5CDS-intronENST00000418483ENST00000545131MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000361114ENST00000372141MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000361114ENST00000372142MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000361114ENST00000404547MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000361114ENST00000404576MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000361114ENST00000556918MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398761ENST00000372141MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398761ENST00000372142MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398761ENST00000404547MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398761ENST00000404576MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398761ENST00000556918MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398763ENST00000372141MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398763ENST00000372142MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398763ENST00000404547MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398763ENST00000404576MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000398763ENST00000556918MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000401998ENST00000372141MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000401998ENST00000372142MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000401998ENST00000404547MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000401998ENST00000404576MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000401998ENST00000556918MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000418483ENST00000372141MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000418483ENST00000372142MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000418483ENST00000404547MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000418483ENST00000404576MICU1chr10

74234858

-NRG3chr10

84118495

+
Frame-shiftENST00000418483ENST00000556918MICU1chr10

74234858

-NRG3chr10

84118495

+
intron-3CDSENST00000604025ENST00000372141MICU1chr10

74234858

-NRG3chr10

84118495

+
intron-3CDSENST00000604025ENST00000372142MICU1chr10

74234858

-NRG3chr10

84118495

+
intron-3CDSENST00000604025ENST00000404547MICU1chr10

74234858

-NRG3chr10

84118495

+
intron-3CDSENST00000604025ENST00000404576MICU1chr10

74234858

-NRG3chr10

84118495

+
intron-3CDSENST00000604025ENST00000556918MICU1chr10

74234858

-NRG3chr10

84118495

+
intron-intronENST00000604025ENST00000537893MICU1chr10

74234858

-NRG3chr10

84118495

+
intron-intronENST00000604025ENST00000545131MICU1chr10

74234858

-NRG3chr10

84118495

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

check buttonDeepORF 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.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score

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Fusion Genomic Features for MICU1-NRG3


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.
genomic feature of top 1%

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Fusion Protein Features for MICU1-NRG3


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:74234858/:84118495)
- 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
MICU1

Q9BPX6

NRG3

P56975

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}.FUNCTION: Direct ligand for the ERBB4 tyrosine kinase receptor. Binding results in ligand-stimulated tyrosine phosphorylation and activation of the receptor. Does not bind to the EGF receptor, ERBB2 or ERBB3 receptors. May be a survival factor for oligodendrocytes. {ECO:0000269|PubMed:16478787, ECO:0000269|PubMed:9275162}.

check buttonRetention 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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for MICU1-NRG3


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for MICU1-NRG3


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for MICU1-NRG3


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for MICU1-NRG3


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource