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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:KDM5A-MBP

Fusion Protein Summary

Fusion gene summary

Fusion partner gene information	Fusion gene name: KDM5A-MBP
	FusionPDB ID: 41853
	FusionGDB2.0 ID: 41853
		Hgene	Tgene
	Gene symbol	KDM5A	MBP
	Gene ID	5927	5553
	Gene name	lysine demethylase 5A	proteoglycan 2, pro eosinophil major basic protein
	Synonyms	RBBP-2\|RBBP2\|RBP2	BMPG\|MBP\|MBP1\|proMBP
	Cytomap	12p13.33	11q12.1
	Type of gene	protein-coding	protein-coding
	Description	lysine-specific demethylase 5AJumonji, AT rich interactive domain 1A (RBP2-like)histone demethylase JARID1Ajumonji/ARID domain-containing protein 1Alysine (K)-specific demethylase 5Aretinoblastoma binding protein 2	bone marrow proteoglycaneosinophil granule major basic proteineosinophil major basic proteinnatural killer cell activatorproteoglycan 2 preproproteinproteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein)
	Modification date	20200313	20200313
	UniProtAcc	P29375	P02686
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000382815, ENST00000399788, ENST00000540838,	ENST00000354542, ENST00000359645, ENST00000397860, ENST00000397863, ENST00000397869, ENST00000487778, ENST00000526111, ENST00000527041, ENST00000528160, ENST00000578193, ENST00000579129, ENST00000580402, ENST00000355994, ENST00000382582, ENST00000397865, ENST00000397866, ENST00000397875,
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)	* DoF score	11 X 15 X 6=990	32 X 27 X 4=3456
	# samples	18	32
	** MAII score	log2(18/990*10)=-2.4594316186373 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(32/3456*10)=-3.43295940727611 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)	PubMed: KDM5A [Title/Abstract] AND MBP [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	KDM5A(498092)-MBP(74696852), # samples:2
Anticipated loss of major functional domain due to fusion event.	KDM5A-MBP 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. KDM5A-MBP 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. KDM5A-MBP 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. KDM5A-MBP 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	KDM5A	GO:0034720	histone H3-K4 demethylation	18270511
Hgene	KDM5A	GO:0045893	positive regulation of transcription, DNA-templated	11358960

Fusion gene breakpoints across KDM5A (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 MBP (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
ChiTaRS5.0	N/A	DB177382	KDM5A	chr12	498092	-	MBP	chr18	74696852	-
ChiTaRS5.0	N/A	DB177419	KDM5A	chr12	498092	-	MBP	chr18	74696852	-

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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)
ENST00000399788	KDM5A	chr12	498092	-	ENST00000382582	MBP	chr18	74696852	-	2293	528	271	732	153
ENST00000399788	KDM5A	chr12	498092	-	ENST00000355994	MBP	chr18	74696852	-	2286	528	271	732	153
ENST00000399788	KDM5A	chr12	498092	-	ENST00000397875	MBP	chr18	74696852	-	2268	528	271	732	153
ENST00000399788	KDM5A	chr12	498092	-	ENST00000397866	MBP	chr18	74696852	-	2268	528	271	732	153
ENST00000399788	KDM5A	chr12	498092	-	ENST00000397865	MBP	chr18	74696852	-	2259	528	271	732	153
ENST00000382815	KDM5A	chr12	498092	-	ENST00000382582	MBP	chr18	74696852	-	2293	528	271	732	153
ENST00000382815	KDM5A	chr12	498092	-	ENST00000355994	MBP	chr18	74696852	-	2286	528	271	732	153
ENST00000382815	KDM5A	chr12	498092	-	ENST00000397875	MBP	chr18	74696852	-	2268	528	271	732	153
ENST00000382815	KDM5A	chr12	498092	-	ENST00000397866	MBP	chr18	74696852	-	2268	528	271	732	153
ENST00000382815	KDM5A	chr12	498092	-	ENST00000397865	MBP	chr18	74696852	-	2259	528	271	732	153

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
ENST00000399788	ENST00000382582	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.7922183	0.20778173
ENST00000399788	ENST00000355994	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.8134155	0.18658446
ENST00000399788	ENST00000397875	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.80762714	0.19237286
ENST00000399788	ENST00000397866	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.80762714	0.19237286
ENST00000399788	ENST00000397865	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.7876818	0.2123182
ENST00000382815	ENST00000382582	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.7922183	0.20778173
ENST00000382815	ENST00000355994	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.8134155	0.18658446
ENST00000382815	ENST00000397875	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.80762714	0.19237286
ENST00000382815	ENST00000397866	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.80762714	0.19237286
ENST00000382815	ENST00000397865	KDM5A	chr12	498092	-	MBP	chr18	74696852	-	0.7876818	0.2123182

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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

>41853_41853_1_KDM5A-MBP_KDM5A_chr12_498092_ENST00000382815_MBP_chr18_74696852_ENST00000355994_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

>41853_41853_2_KDM5A-MBP_KDM5A_chr12_498092_ENST00000382815_MBP_chr18_74696852_ENST00000382582_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

>41853_41853_3_KDM5A-MBP_KDM5A_chr12_498092_ENST00000382815_MBP_chr18_74696852_ENST00000397865_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

>41853_41853_4_KDM5A-MBP_KDM5A_chr12_498092_ENST00000382815_MBP_chr18_74696852_ENST00000397866_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

>41853_41853_5_KDM5A-MBP_KDM5A_chr12_498092_ENST00000382815_MBP_chr18_74696852_ENST00000397875_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

>41853_41853_6_KDM5A-MBP_KDM5A_chr12_498092_ENST00000399788_MBP_chr18_74696852_ENST00000355994_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

>41853_41853_7_KDM5A-MBP_KDM5A_chr12_498092_ENST00000399788_MBP_chr18_74696852_ENST00000382582_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

>41853_41853_8_KDM5A-MBP_KDM5A_chr12_498092_ENST00000399788_MBP_chr18_74696852_ENST00000397865_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

>41853_41853_9_KDM5A-MBP_KDM5A_chr12_498092_ENST00000399788_MBP_chr18_74696852_ENST00000397866_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

>41853_41853_10_KDM5A-MBP_KDM5A_chr12_498092_ENST00000399788_MBP_chr18_74696852_ENST00000397875_length(amino acids)=153AA_BP=85
MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA

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

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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/chr12:498092/chr18:74696852)
- 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
KDM5A P29375	MBP P02686
FUNCTION: Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Regulates specific gene transcription through DNA-binding on 5'-CCGCCC-3' motif (PubMed:18270511). May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation (PubMed:19430464). May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity). Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells (PubMed:27427228). {ECO:0000250\|UniProtKB:Q3UXZ9, ECO:0000269\|PubMed:11358960, ECO:0000269\|PubMed:15949438, ECO:0000269\|PubMed:17320160, ECO:0000269\|PubMed:17320161, ECO:0000269\|PubMed:17320163, ECO:0000269\|PubMed:18270511, ECO:0000269\|PubMed:19430464, ECO:0000269\|PubMed:27427228}.	FUNCTION: The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation. {ECO:0000269\|PubMed:8544862}.

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

MBP

chr12:498092

chr18:74696852

ENST00000359645

179_222

132.0

187.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 1

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000359645

246_256

132.0

187.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 2

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000382582

179_222

143.0

198.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 1

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000382582

246_256

143.0

198.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 2

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000397860

179_222

198.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 1

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000397860

246_256

198.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 2

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000397863

179_222

198.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 1

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000397863

246_256

198.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 2

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000397865

179_222

106.0

161.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 1

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000397865

246_256

106.0

161.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 2

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000397866

179_222

117.0

172.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 1

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000397866

246_256

117.0

172.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 2

- 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

KDM5A

chr12:498092

chr18:74696852

ENST00000399788

1492_1587

55.0

1691.0

Compositional bias

Note=Lys-rich

Hgene

KDM5A

chr12:498092

chr18:74696852

ENST00000399788

19_60

55.0

1691.0

Domain

JmjN

Hgene

KDM5A

chr12:498092

chr18:74696852

ENST00000399788

437_603

55.0

1691.0

Domain

JmjC

Hgene

KDM5A

chr12:498092

chr18:74696852

ENST00000399788

84_174

55.0

1691.0

Domain

ARID

Hgene

KDM5A

chr12:498092

chr18:74696852

ENST00000399788

419_423

55.0

1691.0

Motif

GSGFP motif

Hgene

KDM5A

chr12:498092

chr18:74696852

ENST00000399788

1161_1218

55.0

1691.0

Zinc finger

PHD-type 2

Hgene

KDM5A

chr12:498092

chr18:74696852

ENST00000399788

1607_1661

55.0

1691.0

Zinc finger

PHD-type 3

Hgene

KDM5A

chr12:498092

chr18:74696852

ENST00000399788

293_343

55.0

1691.0

Zinc finger

PHD-type 1

Hgene

KDM5A

chr12:498092

chr18:74696852

ENST00000399788

676_728

55.0

1691.0

Zinc finger

C5HC2

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000355994

179_222

250.0

305.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 1

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000355994

246_256

250.0

305.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 2

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000580402

179_222

250.0

305.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 1

Tgene

MBP

chr12:498092

chr18:74696852

ENST00000580402

246_256

250.0

305.0

Region

Note=Induces experimental autoimmune encephalomyelitis (EAE) 2

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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 >>>127_KDM5A_498092_MBP_74696852_ranked_0.pdb	KDM5A	498092	498092	ENST00000397865	MBP	chr18	74696852	-	MSGDLNGLSGLQPAFLHRFPTGTPPPPRPLQWRAWGRGATRRSSCHRQSAPSLSRVGRSSQIRSALSAASGLWRRKPASAKFGRPRGPKA	153

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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.

KDM5A_pLDDT.png

MBP_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
KDM5A
MBP

- 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 KDM5A-MBP

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 KDM5A-MBP

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