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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:IKZF2-MICU2

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: IKZF2-MICU2
	FusionPDB ID: 39399
	FusionGDB2.0 ID: 39399
		Hgene	Tgene
	Gene symbol	IKZF2	MICU2
	Gene ID	22807	221154
	Gene name	IKAROS family zinc finger 2	mitochondrial calcium uptake 2
	Synonyms	ANF1A2\|HELIOS\|ZNF1A2\|ZNFN1A2	1110008L20Rik\|EFHA1
	Cytomap	2q34	13q12.11
	Type of gene	protein-coding	protein-coding
	Description	zinc finger protein Heliosikaros family zinc finger protein 2zinc finger DNA binding protein Helioszinc finger protein, subfamily 1A, 2 (Helios)	calcium uptake protein 2, mitochondrialEF hand domain family A1EF hand domain family, member A1EF-hand domain-containing family member A1Smhs2 homolog
	Modification date	20200313	20200315
	UniProtAcc	Q9UKS7	Q8IYU8
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000342002, ENST00000374319, ENST00000413091, ENST00000421754, ENST00000434687, ENST00000451136, ENST00000457361, ENST00000374327, ENST00000442445,	ENST00000479790, ENST00000382374,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	7 X 7 X 5=245	13 X 13 X 6=1014
	# samples	7	13
	** MAII score	log2(7/245*10)=-1.8073549220576 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(13/1014*10)=-2.96347412397489 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: IKZF2 [Title/Abstract] AND MICU2 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	IKZF2(213914437)-MICU2(22069457), # samples:2
Anticipated loss of major functional domain due to fusion event.	IKZF2-MICU2 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. IKZF2-MICU2 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. IKZF2-MICU2 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. IKZF2-MICU2 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	MICU2	GO:0006851	mitochondrial calcium ion transmembrane transport	24560927
Tgene	MICU2	GO:0051562	negative regulation of mitochondrial calcium ion concentration	24560927

Fusion gene breakpoints across IKZF2 (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 MICU2 (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	PRAD	TCGA-EJ-5512-01A	IKZF2	chr2	213914437	-	MICU2	chr13	22069457	-
ChimerDB4	PRAD	TCGA-EJ-5512	IKZF2	chr2	213914437	-	MICU2	chr13	22069457	-

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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)
ENST00000457361	IKZF2	chr2	213914437	-	ENST00000382374	MICU2	chr13	22069457	-	1555	743	145	1005	286
ENST00000342002	IKZF2	chr2	213914437	-	ENST00000382374	MICU2	chr13	22069457	-	1555	743	145	1005	286
ENST00000434687	IKZF2	chr2	213914437	-	ENST00000382374	MICU2	chr13	22069457	-	1696	884	304	1146	280
ENST00000374319	IKZF2	chr2	213914437	-	ENST00000382374	MICU2	chr13	22069457	-	1618	806	304	1068	254
ENST00000451136	IKZF2	chr2	213914437	-	ENST00000382374	MICU2	chr13	22069457	-	1308	496	0	758	252
ENST00000413091	IKZF2	chr2	213914437	-	ENST00000382374	MICU2	chr13	22069457	-	1386	574	0	836	278
ENST00000421754	IKZF2	chr2	213914437	-	ENST00000382374	MICU2	chr13	22069457	-	1308	496	0	758	252

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
ENST00000457361	ENST00000382374	IKZF2	chr2	213914437	-	MICU2	chr13	22069457	-	0.000602682	0.9993973
ENST00000342002	ENST00000382374	IKZF2	chr2	213914437	-	MICU2	chr13	22069457	-	0.000602682	0.9993973
ENST00000434687	ENST00000382374	IKZF2	chr2	213914437	-	MICU2	chr13	22069457	-	0.000932356	0.9990677
ENST00000374319	ENST00000382374	IKZF2	chr2	213914437	-	MICU2	chr13	22069457	-	0.001308477	0.9986915
ENST00000451136	ENST00000382374	IKZF2	chr2	213914437	-	MICU2	chr13	22069457	-	0.001385558	0.99861443
ENST00000413091	ENST00000382374	IKZF2	chr2	213914437	-	MICU2	chr13	22069457	-	0.000913586	0.9990864
ENST00000421754	ENST00000382374	IKZF2	chr2	213914437	-	MICU2	chr13	22069457	-	0.001385558	0.99861443

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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

>39399_39399_1_IKZF2-MICU2_IKZF2_chr2_213914437_ENST00000342002_MICU2_chr13_22069457_ENST00000382374_length(amino acids)=286AA_BP=199
MEMHCTLTMETEAIDGYITCDNELSPEREHSNMAIDLTSSTPNGQHASPSHMTSTNSVKLEMQSDEECDRKPLSREDEIRGHDEGSSLEE
PLIESSEVADNRKVQELQGEGGIRLPNGKLKCDVCGMVCIGPNVLMVHKRSHTGERPFHCNQCGASFTQKGNLLRHIKLHSGEKPFKCPF
CSYACRRRDALTGHLRTHSAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRMHRGLWVPQHQSIQEYWKCVKKES

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

>39399_39399_2_IKZF2-MICU2_IKZF2_chr2_213914437_ENST00000374319_MICU2_chr13_22069457_ENST00000382374_length(amino acids)=254AA_BP=167
MTMETEAIDGYITCDNELSPEREHSNMAIDLTSSTPNGQHASPSHMTSTNSVKLEMQSDEECDRKPLSREDEIRGHDEGSSLEEPLIESS
EVADNRKVQELQGEGGIRLPNGERPFHCNQCGASFTQKGNLLRHIKLHSGEKPFKCPFCSYACRRRDALTGHLRTHSAEFKRAVKVATGQ

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

>39399_39399_3_IKZF2-MICU2_IKZF2_chr2_213914437_ENST00000413091_MICU2_chr13_22069457_ENST00000382374_length(amino acids)=278AA_BP=191
METEAIDGYITCDNELSPEREHSNMAIDLTSSTPNGQHASPSHMTSTNSVKLEMQSDEECDRKPLSREDEIRGHDEGSSLEEPLIESSEV
ADNRKVQELQGEGGIRLPNGKLKCDVCGMVCIGPNVLMVHKRSHTGERPFHCNQCGASFTQKGNLLRHIKLHSGEKPFKCPFCSYACRRR
DALTGHLRTHSAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRMHRGLWVPQHQSIQEYWKCVKKESIKGVKEVW

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

>39399_39399_4_IKZF2-MICU2_IKZF2_chr2_213914437_ENST00000421754_MICU2_chr13_22069457_ENST00000382374_length(amino acids)=252AA_BP=165
METEAIDGYITCDNELSPEREHSNMAIDLTSSTPNGQHASPSHMTSTNSVKLEMQSDEECDRKPLSREDEIRGHDEGSSLEEPLIESSEV
ADNRKVQELQGEGGIRLPNGERPFHCNQCGASFTQKGNLLRHIKLHSGEKPFKCPFCSYACRRRDALTGHLRTHSAEFKRAVKVATGQEL

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

>39399_39399_5_IKZF2-MICU2_IKZF2_chr2_213914437_ENST00000434687_MICU2_chr13_22069457_ENST00000382374_length(amino acids)=280AA_BP=193
MTMETEAIDGYITCDNELSPEREHSNMAIDLTSSTPNGQHASPSHMTSTNSVKLEMQSDEECDRKPLSREDEIRGHDEGSSLEEPLIESS
EVADNRKVQELQGEGGIRLPNGKLKCDVCGMVCIGPNVLMVHKRSHTGERPFHCNQCGASFTQKGNLLRHIKLHSGEKPFKCPFCSYACR
RRDALTGHLRTHSAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRMHRGLWVPQHQSIQEYWKCVKKESIKGVKE

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

>39399_39399_6_IKZF2-MICU2_IKZF2_chr2_213914437_ENST00000451136_MICU2_chr13_22069457_ENST00000382374_length(amino acids)=252AA_BP=165
METEAIDGYITCDNELSPEREHSNMAIDLTSSTPNGQHASPSHMTSTNSVKLEMQSDEECDRKPLSREDEIRGHDEGSSLEEPLIESSEV
ADNRKVQELQGEGGIRLPNGERPFHCNQCGASFTQKGNLLRHIKLHSGEKPFKCPFCSYACRRRDALTGHLRTHSAEFKRAVKVATGQEL

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

>39399_39399_7_IKZF2-MICU2_IKZF2_chr2_213914437_ENST00000457361_MICU2_chr13_22069457_ENST00000382374_length(amino acids)=286AA_BP=199
MEMHCTLTMETEAIDGYITCDNELSPEREHSNMAIDLTSSTPNGQHASPSHMTSTNSVKLEMQSDEECDRKPLSREDEIRGHDEGSSLEE
PLIESSEVADNRKVQELQGEGGIRLPNGKLKCDVCGMVCIGPNVLMVHKRSHTGERPFHCNQCGASFTQKGNLLRHIKLHSGEKPFKCPF
CSYACRRRDALTGHLRTHSAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRMHRGLWVPQHQSIQEYWKCVKKES

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

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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/chr2:213914437/chr13:22069457)
- 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
IKZF2 Q9UKS7	MICU2 Q8IYU8
FUNCTION: Associates with Ikaros at centromeric heterochromatin.	FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:24503055, PubMed:24560927, PubMed:26903221). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting calcium, avoiding energy dissipation and cell-death triggering (PubMed:24560927). {ECO:0000269\|PubMed:24503055, ECO:0000269\|PubMed:24560927, ECO:0000269\|PubMed:26387864, ECO:0000269\|PubMed:26903221}.

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

IKZF2

chr2:213914437

chr13:22069457

ENST00000374319

112_134

165.33333333333334

501.0

Zinc finger

C2H2-type 1

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000374319

140_162

165.33333333333334

501.0

Zinc finger

C2H2-type 2

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000434687

112_134

191.33333333333334

527.0

Zinc finger

C2H2-type 1

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000434687

140_162

191.33333333333334

527.0

Zinc finger

C2H2-type 2

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000434687

168_190

191.33333333333334

527.0

Zinc finger

C2H2-type 3

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000457361

112_134

191.33333333333334

527.0

Zinc finger

C2H2-type 1

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000457361

140_162

191.33333333333334

527.0

Zinc finger

C2H2-type 2

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000457361

168_190

191.33333333333334

527.0

Zinc finger

C2H2-type 3

Tgene

MICU2

chr2:213914437

chr13:22069457

ENST00000382374

362_397

347.3333333333333

435.0

Domain

EF-hand 4

- 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

IKZF2

chr2:213914437

chr13:22069457

ENST00000374319

168_190

165.33333333333334

501.0

Zinc finger

C2H2-type 3

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000374319

196_219

165.33333333333334

501.0

Zinc finger

C2H2-type 4

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000374319

471_493

165.33333333333334

501.0

Zinc finger

C2H2-type 5

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000374319

499_523

165.33333333333334

501.0

Zinc finger

C2H2-type 6

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000434687

196_219

191.33333333333334

527.0

Zinc finger

C2H2-type 4

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000434687

471_493

191.33333333333334

527.0

Zinc finger

C2H2-type 5

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000434687

499_523

191.33333333333334

527.0

Zinc finger

C2H2-type 6

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000457361

196_219

191.33333333333334

527.0

Zinc finger

C2H2-type 4

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000457361

471_493

191.33333333333334

527.0

Zinc finger

C2H2-type 5

Hgene

IKZF2

chr2:213914437

chr13:22069457

ENST00000457361

499_523

191.33333333333334

527.0

Zinc finger

C2H2-type 6

Tgene

MICU2

chr2:213914437

chr13:22069457

ENST00000382374

2_50

347.3333333333333

435.0

Compositional bias

Note=Ala-rich

Tgene

MICU2

chr2:213914437

chr13:22069457

ENST00000382374

172_207

347.3333333333333

435.0

Domain

EF-hand 1

Tgene

MICU2

chr2:213914437

chr13:22069457

ENST00000382374

227_262

347.3333333333333

435.0

Domain

EF-hand 2

Tgene

MICU2

chr2:213914437

chr13:22069457

ENST00000382374

293_328

347.3333333333333

435.0

Domain

EF-hand 3

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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 >>>501_IKZF2_213914437_MICU2_22069457_ranked_0.pdb	IKZF2	213914437	213914437	ENST00000382374	MICU2	chr13	22069457	-	MEMHCTLTMETEAIDGYITCDNELSPEREHSNMAIDLTSSTPNGQHASPSHMTSTNSVKLEMQSDEECDRKPLSREDEIRGHDEGSSLEE PLIESSEVADNRKVQELQGEGGIRLPNGKLKCDVCGMVCIGPNVLMVHKRSHTGERPFHCNQCGASFTQKGNLLRHIKLHSGEKPFKCPF CSYACRRRDALTGHLRTHSAEFKRAVKVATGQELSNNILDTVFKIFDLDGDECLSHEEFLGVLKNRMHRGLWVPQHQSIQEYWKCVKKES	286

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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.

IKZF2_pLDDT.png

MICU2_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
IKZF2
MICU2

- 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 IKZF2-MICU2

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 IKZF2-MICU2

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