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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:ESRRB-MLH1 (FusionGDB2 ID:27586)

Fusion Gene Summary for ESRRB-MLH1

check button Fusion gene summary
Fusion gene informationFusion gene name: ESRRB-MLH1
Fusion gene ID: 27586
HgeneTgene
Gene symbol

ESRRB

MLH1

Gene ID

2103

4292

Gene nameestrogen related receptor betamutL homolog 1
SynonymsDFNB35|ERR beta-2|ERR2|ERRb|ERRbeta2|ESRL2|NR3B2COCA2|FCC2|HNPCC|HNPCC2|hMLH1
Cytomap

14q24.3

3p22.2

Type of geneprotein-codingprotein-coding
Descriptionsteroid hormone receptor ERR2estrogen receptor-like 2estrogen-related nuclear receptor betanuclear receptor ERRB2nuclear receptor subfamily 3 group B member 2orphan nuclear receptorDNA mismatch repair protein Mlh1mutL homolog 1, colon cancer, nonpolyposis type 2
Modification date2020032620200327
UniProtAcc

O95718

P40692

Ensembl transtripts involved in fusion geneENST00000261532, ENST00000380887, 
ENST00000507951, ENST00000509242, 
ENST00000556177, 		ENST00000231790, 
ENST00000435176, ENST00000455445, 
ENST00000458205, ENST00000492474, 
ENST00000536378, ENST00000539477, 
Fusion gene scores* DoF score4 X 4 X 1=168 X 18 X 5=720
# samples 420
** MAII scorelog2(4/16*10)=1.32192809488736
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0		log2(20/720*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: ESRRB [Title/Abstract] AND MLH1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointESRRB(76778314)-MLH1(37090623), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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
HgeneESRRB

GO:0006355

regulation of transcription, DNA-templated

23836911

HgeneESRRB

GO:0019827

stem cell population maintenance

25522312


check buttonFusion gene breakpoints across ESRRB (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 MLH1 (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
ChiTaRS5.0N/AAI821421ESRRBchr14

76778314

-MLH1chr3

37090623

+


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Fusion Gene ORF analysis for ESRRB-MLH1

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
intron-intronENST00000261532ENST00000231790ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000261532ENST00000435176ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000261532ENST00000455445ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000261532ENST00000458205ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000261532ENST00000492474ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000261532ENST00000536378ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000261532ENST00000539477ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000380887ENST00000231790ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000380887ENST00000435176ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000380887ENST00000455445ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000380887ENST00000458205ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000380887ENST00000492474ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000380887ENST00000536378ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000380887ENST00000539477ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000507951ENST00000231790ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000507951ENST00000435176ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000507951ENST00000455445ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000507951ENST00000458205ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000507951ENST00000492474ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000507951ENST00000536378ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000507951ENST00000539477ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000509242ENST00000231790ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000509242ENST00000435176ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000509242ENST00000455445ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000509242ENST00000458205ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000509242ENST00000492474ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000509242ENST00000536378ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000509242ENST00000539477ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000556177ENST00000231790ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000556177ENST00000435176ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000556177ENST00000455445ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000556177ENST00000458205ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000556177ENST00000492474ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000556177ENST00000536378ESRRBchr14

76778314

-MLH1chr3

37090623

+
intron-intronENST00000556177ENST00000539477ESRRBchr14

76778314

-MLH1chr3

37090623

+

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 ESRRB-MLH1


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.

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Fusion Protein Features for ESRRB-MLH1


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/:76778314/:37090623)
- 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
ESRRB

O95718

MLH1

P40692

FUNCTION: [Isoform 3]: Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity (PubMed:17920186, PubMed:19755138). Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells. Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:23836911). Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (PubMed:17920186, PubMed:19755138). During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation. This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity). {ECO:0000250|UniProtKB:Q61539, ECO:0000269|PubMed:17920186, ECO:0000269|PubMed:19755138, ECO:0000269|PubMed:23836911}.; FUNCTION: [Isoform 1]: Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity. Positively regulates ESR1 transcriptional activity upon E2 stimulation. {ECO:0000269|PubMed:19755138}.FUNCTION: Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis. {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974, ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:9311737}.

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 ESRRB-MLH1


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 ESRRB-MLH1


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 ESRRB-MLH1


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 ESRRB-MLH1


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