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	Fusion Gene Summary
	Fusion Gene Sample Information
	Fusion ORF Analysis
	Fusion Amino Acid Sequences
	Fusion Protein Functional Features
	Fusion Protein-Protein Interaction
	Related drugs with this fusion protein
	Related disease with this fusion protein

Fusion Protein:ING4-A2ML1

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: ING4-A2ML1
	FusionPDB ID: 39745
	FusionGDB2.0 ID: 39745
		Hgene	Tgene
	Gene symbol	ING4	A2ML1
	Gene ID	51147	144568
	Gene name	inhibitor of growth family member 4	alpha-2-macroglobulin like 1
	Synonyms	my036\|p29ING4	CPAMD9\|OMS\|p170
	Cytomap	12p13.31	12p13.31
	Type of gene	protein-coding	protein-coding
	Description	inhibitor of growth protein 4brain my036 proteincandidate tumor suppressor p33 ING1 homolog	alpha-2-macroglobulin-like protein 1C3 and PZP-like, alpha-2-macroglobulin domain containing 9
	Modification date	20200322	20200313
	UniProtAcc	Q9UNL4	A8K2U0
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000341550, ENST00000396807, ENST00000412586, ENST00000423703, ENST00000444704, ENST00000446105, ENST00000486287,	ENST00000540049, ENST00000299698, ENST00000539547,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	3 X 3 X 3=27	7 X 6 X 4=168
	# samples	3	6
	** MAII score	log2(3/27*10)=0.15200309344505 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0	log2(6/168*10)=-1.48542682717024 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: ING4 [Title/Abstract] AND A2ML1 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	ING4(6772231)-A2ML1(9027021), # samples:3
Anticipated loss of major functional domain due to fusion event.	ING4-A2ML1 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. ING4-A2ML1 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	ING4	GO:0006260	DNA replication	16387653
Hgene	ING4	GO:0006473	protein acetylation	12750254
Hgene	ING4	GO:0006915	apoptotic process	15251430
Hgene	ING4	GO:0006978	DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator	16387653
Hgene	ING4	GO:0007050	cell cycle arrest	15251430
Hgene	ING4	GO:0008285	negative regulation of cell proliferation	12750254\|15251430
Hgene	ING4	GO:0043065	positive regulation of apoptotic process	16387653
Hgene	ING4	GO:0043966	histone H3 acetylation	16387653
Hgene	ING4	GO:0043981	histone H4-K5 acetylation	16387653
Hgene	ING4	GO:0043982	histone H4-K8 acetylation	16387653
Hgene	ING4	GO:0043983	histone H4-K12 acetylation	16387653
Hgene	ING4	GO:0043984	histone H4-K16 acetylation	16387653
Hgene	ING4	GO:0045892	negative regulation of transcription, DNA-templated	15029197
Hgene	ING4	GO:0045926	negative regulation of growth	12750254
Tgene	A2ML1	GO:0052548	regulation of endopeptidase activity	16298998

Fusion gene breakpoints across ING4 (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 A2ML1 (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	SKCM	TCGA-D3-A3CC-06A	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+

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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)
ENST00000341550	ING4	chr12	6772231	-	ENST00000299698	A2ML1	chr12	9027021	+	957	84	786	496	96
ENST00000341550	ING4	chr12	6772231	-	ENST00000539547	A2ML1	chr12	9027021	+	628	84	27	227	66
ENST00000396807	ING4	chr12	6772231	-	ENST00000299698	A2ML1	chr12	9027021	+	949	76	778	488	96
ENST00000396807	ING4	chr12	6772231	-	ENST00000539547	A2ML1	chr12	9027021	+	620	76	19	219	66
ENST00000446105	ING4	chr12	6772231	-	ENST00000299698	A2ML1	chr12	9027021	+	951	78	780	490	96
ENST00000446105	ING4	chr12	6772231	-	ENST00000539547	A2ML1	chr12	9027021	+	622	78	21	221	66
ENST00000444704	ING4	chr12	6772231	-	ENST00000299698	A2ML1	chr12	9027021	+	910	37	739	449	96
ENST00000444704	ING4	chr12	6772231	-	ENST00000539547	A2ML1	chr12	9027021	+	581	37	4	180	58
ENST00000423703	ING4	chr12	6772231	-	ENST00000299698	A2ML1	chr12	9027021	+	910	37	739	449	96
ENST00000423703	ING4	chr12	6772231	-	ENST00000539547	A2ML1	chr12	9027021	+	581	37	4	180	58
ENST00000412586	ING4	chr12	6772231	-	ENST00000299698	A2ML1	chr12	9027021	+	910	37	739	449	96
ENST00000412586	ING4	chr12	6772231	-	ENST00000539547	A2ML1	chr12	9027021	+	581	37	4	180	58

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
ENST00000341550	ENST00000299698	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.92511386	0.07488609
ENST00000341550	ENST00000539547	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.32635444	0.67364556
ENST00000396807	ENST00000299698	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.89101493	0.108985096
ENST00000396807	ENST00000539547	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.21817514	0.7818249
ENST00000446105	ENST00000299698	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.9072365	0.09276349
ENST00000446105	ENST00000539547	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.24214247	0.7578575
ENST00000444704	ENST00000299698	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.85087997	0.14912003
ENST00000444704	ENST00000539547	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.13617256	0.8638274
ENST00000423703	ENST00000299698	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.85087997	0.14912003
ENST00000423703	ENST00000539547	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.13617256	0.8638274
ENST00000412586	ENST00000299698	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.85087997	0.14912003
ENST00000412586	ENST00000539547	ING4	chr12	6772231	-	A2ML1	chr12	9027021	+	0.13617256	0.8638274

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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

>39745_39745_1_ING4-A2ML1_ING4_chr12_6772231_ENST00000341550_A2ML1_chr12_9027021_ENST00000299698_length(amino acids)=96AA_BP=
MQPPPPVLRRFSCLGLPRGCDYRPVPPHQANLCIVSRDGFYHVGQAGLELLTSSDPPTSQSQSAGITGVSHRIRPRKTFLSSLVHPLPPS

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

>39745_39745_2_ING4-A2ML1_ING4_chr12_6772231_ENST00000341550_A2ML1_chr12_9027021_ENST00000539547_length(amino acids)=66AA_BP=19

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

>39745_39745_3_ING4-A2ML1_ING4_chr12_6772231_ENST00000396807_A2ML1_chr12_9027021_ENST00000299698_length(amino acids)=96AA_BP=
MQPPPPVLRRFSCLGLPRGCDYRPVPPHQANLCIVSRDGFYHVGQAGLELLTSSDPPTSQSQSAGITGVSHRIRPRKTFLSSLVHPLPPS

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

>39745_39745_4_ING4-A2ML1_ING4_chr12_6772231_ENST00000396807_A2ML1_chr12_9027021_ENST00000539547_length(amino acids)=66AA_BP=19

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

>39745_39745_5_ING4-A2ML1_ING4_chr12_6772231_ENST00000412586_A2ML1_chr12_9027021_ENST00000299698_length(amino acids)=96AA_BP=
MQPPPPVLRRFSCLGLPRGCDYRPVPPHQANLCIVSRDGFYHVGQAGLELLTSSDPPTSQSQSAGITGVSHRIRPRKTFLSSLVHPLPPS

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

>39745_39745_6_ING4-A2ML1_ING4_chr12_6772231_ENST00000412586_A2ML1_chr12_9027021_ENST00000539547_length(amino acids)=58AA_BP=11

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

>39745_39745_7_ING4-A2ML1_ING4_chr12_6772231_ENST00000423703_A2ML1_chr12_9027021_ENST00000299698_length(amino acids)=96AA_BP=
MQPPPPVLRRFSCLGLPRGCDYRPVPPHQANLCIVSRDGFYHVGQAGLELLTSSDPPTSQSQSAGITGVSHRIRPRKTFLSSLVHPLPPS

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

>39745_39745_8_ING4-A2ML1_ING4_chr12_6772231_ENST00000423703_A2ML1_chr12_9027021_ENST00000539547_length(amino acids)=58AA_BP=11

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

>39745_39745_9_ING4-A2ML1_ING4_chr12_6772231_ENST00000444704_A2ML1_chr12_9027021_ENST00000299698_length(amino acids)=96AA_BP=
MQPPPPVLRRFSCLGLPRGCDYRPVPPHQANLCIVSRDGFYHVGQAGLELLTSSDPPTSQSQSAGITGVSHRIRPRKTFLSSLVHPLPPS

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

>39745_39745_10_ING4-A2ML1_ING4_chr12_6772231_ENST00000444704_A2ML1_chr12_9027021_ENST00000539547_length(amino acids)=58AA_BP=11

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

>39745_39745_11_ING4-A2ML1_ING4_chr12_6772231_ENST00000446105_A2ML1_chr12_9027021_ENST00000299698_length(amino acids)=96AA_BP=
MQPPPPVLRRFSCLGLPRGCDYRPVPPHQANLCIVSRDGFYHVGQAGLELLTSSDPPTSQSQSAGITGVSHRIRPRKTFLSSLVHPLPPS

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

>39745_39745_12_ING4-A2ML1_ING4_chr12_6772231_ENST00000446105_A2ML1_chr12_9027021_ENST00000539547_length(amino acids)=66AA_BP=19

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

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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/chr12:6772231/chr12:9027021)
- 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
ING4 Q9UNL4	A2ML1 A8K2U0
FUNCTION: Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4 (PubMed:16387653). Through chromatin acetylation it may function in DNA replication (PubMed:16387653). May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation (PubMed:15251430, PubMed:15528276). Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA (PubMed:15029197). May also specifically suppress loss of contact inhibition elicited by activated oncogenes such as MYC (PubMed:15029197). Represses hypoxia inducible factor's (HIF) activity by interacting with HIF prolyl hydroxylase 2 (EGLN1) (PubMed:15897452). Can enhance apoptosis induced by serum starvation in mammary epithelial cell line HC11 (By similarity). {ECO:0000250\|UniProtKB:Q8C0D7, ECO:0000269\|PubMed:15029197, ECO:0000269\|PubMed:15251430, ECO:0000269\|PubMed:15528276, ECO:0000269\|PubMed:15897452, ECO:0000269\|PubMed:16387653}.	FUNCTION: Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase (By similarity). Displays inhibitory activity against chymotrypsin, papain, thermolysin, subtilisin A and, to a lesser extent, elastase but not trypsin. May play an important role during desquamation by inhibiting extracellular proteases. {ECO:0000250\|UniProtKB:P01023, ECO:0000269\|PubMed:16298998}.

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

- 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

ING4

chr12:6772231

chr12:9027021

ENST00000341550

25_118

12.333333333333334

249.0

Coiled coil

Ontology_term=ECO:0000269

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000396807

25_118

12.333333333333334

250.0

Coiled coil

Ontology_term=ECO:0000269

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000412586

25_118

12.333333333333334

247.0

Coiled coil

Ontology_term=ECO:0000269

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000423703

25_118

12.333333333333334

177.66666666666666

Coiled coil

Ontology_term=ECO:0000269

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000444704

25_118

12.333333333333334

226.0

Coiled coil

Ontology_term=ECO:0000269

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000446105

25_118

12.333333333333334

246.0

Coiled coil

Ontology_term=ECO:0000269

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000341550

127_148

12.333333333333334

249.0

Motif

Note=Bipartite nuclear localization signal

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000396807

127_148

12.333333333333334

250.0

Motif

Note=Bipartite nuclear localization signal

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000412586

127_148

12.333333333333334

247.0

Motif

Note=Bipartite nuclear localization signal

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000423703

127_148

12.333333333333334

177.66666666666666

Motif

Note=Bipartite nuclear localization signal

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000444704

127_148

12.333333333333334

226.0

Motif

Note=Bipartite nuclear localization signal

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000446105

127_148

12.333333333333334

246.0

Motif

Note=Bipartite nuclear localization signal

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000341550

196_245

12.333333333333334

249.0

Zinc finger

PHD-type

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000396807

196_245

12.333333333333334

250.0

Zinc finger

PHD-type

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000412586

196_245

12.333333333333334

247.0

Zinc finger

PHD-type

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000423703

196_245

12.333333333333334

177.66666666666666

Zinc finger

PHD-type

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000444704

196_245

12.333333333333334

226.0

Zinc finger

PHD-type

Hgene

ING4

chr12:6772231

chr12:9027021

ENST00000446105

196_245

12.333333333333334

246.0

Zinc finger

PHD-type

Tgene

A2ML1

chr12:6772231

chr12:9027021

ENST00000299698

695_726

1407.0

1617.0

Region

Bait region

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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
ING4
A2ML1

- 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 ING4-A2ML1

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 ING4-A2ML1

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