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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:HMGA1-MLH1 (FusionGDB2 ID:36810)

Fusion Gene Summary for HMGA1-MLH1

check button Fusion gene summary
Fusion gene informationFusion gene name: HMGA1-MLH1
Fusion gene ID: 36810
HgeneTgene
Gene symbol

HMGA1

MLH1

Gene ID

3159

4292

Gene namehigh mobility group AT-hook 1mutL homolog 1
SynonymsHMG-R|HMGA1A|HMGIYCOCA2|FCC2|HNPCC|HNPCC2|hMLH1
Cytomap

6p21.31

3p22.2

Type of geneprotein-codingprotein-coding
Descriptionhigh mobility group protein HMG-I/HMG-Yhigh mobility group protein A1high mobility group protein Rhigh-mobility group (nonhistone chromosomal) protein isoforms I and Ynonhistone chromosomal high-mobility group protein HMG-I/HMG-YDNA mismatch repair protein Mlh1mutL homolog 1, colon cancer, nonpolyposis type 2
Modification date2020031520200327
UniProtAcc

P17096

P40692

Ensembl transtripts involved in fusion geneENST00000311487, ENST00000347617, 
ENST00000374116, ENST00000401473, 
ENST00000447654, ENST00000395004, 
ENST00000478214, 		ENST00000231790, 
ENST00000435176, ENST00000455445, 
ENST00000458205, ENST00000536378, 
ENST00000539477, ENST00000492474, 
Fusion gene scores* DoF score13 X 9 X 5=5858 X 18 X 5=720
# samples 1220
** MAII scorelog2(12/585*10)=-2.28540221886225
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
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: HMGA1 [Title/Abstract] AND MLH1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointHMGA1(34213057)-MLH1(37067174), # samples:2
Anticipated loss of major functional domain due to fusion event.HMGA1-MLH1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
HMGA1-MLH1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
HMGA1-MLH1 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
HMGA1-MLH1 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgeneHMGA1

GO:0035986

senescence-associated heterochromatin focus assembly

16901784

HgeneHMGA1

GO:0090402

oncogene-induced cell senescence

16901784


check buttonFusion gene breakpoints across HMGA1 (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/ABC005833HMGA1chr6

34213057

+MLH1chr3

37067174

+
ChiTaRS5.0N/ABC005866HMGA1chr6

34213057

+MLH1chr3

37067174

+


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Fusion Gene ORF analysis for HMGA1-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
3UTR-3CDSENST00000311487ENST00000231790HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000311487ENST00000435176HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000311487ENST00000455445HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000311487ENST00000458205HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000311487ENST00000536378HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000311487ENST00000539477HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000347617ENST00000231790HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000347617ENST00000435176HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000347617ENST00000455445HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000347617ENST00000458205HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000347617ENST00000536378HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000347617ENST00000539477HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000374116ENST00000231790HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000374116ENST00000435176HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000374116ENST00000455445HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000374116ENST00000458205HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000374116ENST00000536378HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000374116ENST00000539477HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000401473ENST00000231790HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000401473ENST00000435176HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000401473ENST00000455445HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000401473ENST00000458205HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000401473ENST00000536378HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000401473ENST00000539477HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000447654ENST00000231790HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000447654ENST00000435176HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000447654ENST00000455445HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000447654ENST00000458205HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000447654ENST00000536378HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-3CDSENST00000447654ENST00000539477HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-intronENST00000311487ENST00000492474HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-intronENST00000347617ENST00000492474HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-intronENST00000374116ENST00000492474HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-intronENST00000401473ENST00000492474HMGA1chr6

34213057

+MLH1chr3

37067174

+
3UTR-intronENST00000447654ENST00000492474HMGA1chr6

34213057

+MLH1chr3

37067174

+
5CDS-intronENST00000395004ENST00000492474HMGA1chr6

34213057

+MLH1chr3

37067174

+
Frame-shiftENST00000395004ENST00000231790HMGA1chr6

34213057

+MLH1chr3

37067174

+
Frame-shiftENST00000395004ENST00000435176HMGA1chr6

34213057

+MLH1chr3

37067174

+
Frame-shiftENST00000395004ENST00000455445HMGA1chr6

34213057

+MLH1chr3

37067174

+
Frame-shiftENST00000395004ENST00000458205HMGA1chr6

34213057

+MLH1chr3

37067174

+
Frame-shiftENST00000395004ENST00000536378HMGA1chr6

34213057

+MLH1chr3

37067174

+
Frame-shiftENST00000395004ENST00000539477HMGA1chr6

34213057

+MLH1chr3

37067174

+
intron-3CDSENST00000478214ENST00000231790HMGA1chr6

34213057

+MLH1chr3

37067174

+
intron-3CDSENST00000478214ENST00000435176HMGA1chr6

34213057

+MLH1chr3

37067174

+
intron-3CDSENST00000478214ENST00000455445HMGA1chr6

34213057

+MLH1chr3

37067174

+
intron-3CDSENST00000478214ENST00000458205HMGA1chr6

34213057

+MLH1chr3

37067174

+
intron-3CDSENST00000478214ENST00000536378HMGA1chr6

34213057

+MLH1chr3

37067174

+
intron-3CDSENST00000478214ENST00000539477HMGA1chr6

34213057

+MLH1chr3

37067174

+
intron-intronENST00000478214ENST00000492474HMGA1chr6

34213057

+MLH1chr3

37067174

+

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 HMGA1-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 HMGA1-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/:34213057/:37067174)
- 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
HMGA1

P17096

MLH1

P40692

FUNCTION: HMG-I/Y bind preferentially to the minor groove of A+T rich regions in double-stranded DNA. It is suggested that these proteins could function in nucleosome phasing and in the 3'-end processing of mRNA transcripts. They are also involved in the transcription regulation of genes containing, or in close proximity to A+T-rich regions.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 HMGA1-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 HMGA1-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 HMGA1-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 HMGA1-MLH1


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