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Center for Computational Systems Medicine level1
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:THRB-LMCD1

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: THRB-LMCD1
FusionPDB ID: 90743
FusionGDB2.0 ID: 90743
HgeneTgene
Gene symbol

THRB

LMCD1

Gene ID

7068

29995

Gene namethyroid hormone receptor betaLIM and cysteine rich domains 1
SynonymsC-ERBA-2|C-ERBA-BETA|ERBA2|GRTH|NR1A2|PRTH|THR1|THRB1|THRB2-
Cytomap

3p24.2

3p25.3

Type of geneprotein-codingprotein-coding
Descriptionthyroid hormone receptor betanuclear receptor subfamily 1 group A member 2oncogene ERBA2thyroid hormone nuclear receptor beta variant 1thyroid hormone receptor, beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian)LIM and cysteine-rich domains protein 1dyxin
Modification date2020031320200313
UniProtAcc.

Q9NZU5

Ensembl transtripts involved in fusion geneENST idsENST00000280696, ENST00000356447, 
ENST00000396671, ENST00000416420, 
ENST00000397386, ENST00000454244, 
ENST00000157600, ENST00000535732, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 9 X 5=4504 X 2 X 3=24
# samples 104
** MAII scorelog2(10/450*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(4/24*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Context (manual curation of fusion genes in FusionPDB)

PubMed: THRB [Title/Abstract] AND LMCD1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)THRB(24184992)-LMCD1(8574423), # samples:3
Anticipated loss of major functional domain due to fusion event.THRB-LMCD1 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.
THRB-LMCD1 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.
THRB-LMCD1 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.
THRB-LMCD1 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.
THRB-LMCD1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
THRB-LMCD1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
THRB-LMCD1 seems lost the major protein functional domain in Hgene 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

check buttonFusion gene breakpoints across THRB (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across LMCD1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
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
ChimerDB4BRCATCGA-A2-A0CW-01ATHRBchr3

24184992

-LMCD1chr3

8574423

+


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Fusion ORF Analysis


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)
ENST00000396671THRBchr324184992-ENST00000157600LMCD1chr38574423+266410873492142597
ENST00000396671THRBchr324184992-ENST00000535732LMCD1chr38574423+178910873491788480
ENST00000356447THRBchr324184992-ENST00000157600LMCD1chr38574423+260010232852078597
ENST00000356447THRBchr324184992-ENST00000535732LMCD1chr38574423+172510232851724479
ENST00000280696THRBchr324184992-ENST00000157600LMCD1chr38574423+260110242232079618
ENST00000280696THRBchr324184992-ENST00000535732LMCD1chr38574423+172610242231725501

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
ENST00000396671ENST00000157600THRBchr324184992-LMCD1chr38574423+0.0056582660.99434173
ENST00000396671ENST00000535732THRBchr324184992-LMCD1chr38574423+0.0101427930.9898572
ENST00000356447ENST00000157600THRBchr324184992-LMCD1chr38574423+0.00472790.9952721
ENST00000356447ENST00000535732THRBchr324184992-LMCD1chr38574423+0.0081094830.99189055
ENST00000280696ENST00000157600THRBchr324184992-LMCD1chr38574423+0.0023448540.99765515
ENST00000280696ENST00000535732THRBchr324184992-LMCD1chr38574423+0.0025804170.9974196

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Fusion Amino Acid Sequences


check button 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

>90743_90743_1_THRB-LMCD1_THRB_chr3_24184992_ENST00000280696_LMCD1_chr3_8574423_ENST00000157600_length(amino acids)=618AA_BP=265
MNQGNKMNYCMQEIYEVHPAAGSNCYMQSTDYYAYFEDSPGYSGCDAQAVPSNNIYMEQAWAVNQPYTCSYPGNMFKSKDSDLDMALNQY
SQPEYFTEEKPTFSQVQSPSYSQKKGYIPSYLDKDELCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRN
QCQECRFKKCIYVGMATDLVLDDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWKQKRKFLMSL
GQLQSARGVACLGCKGTCSGFEPHSWRKICKSCKCSQEDHCLTSDLEDDRKIGRLLMDSKYSTLTARVKGGDGIRIYKRNRMIMTNPIAT
GKDPTFDTITYEWAPPGVTQKLGLQYMELIPKEKQPVTGTEGAFYRRRQLMHQLPIYDQDPSRCRGLLENELKLMEEFVKQYKSEALGVG
EVALPGQGGLPKEEGKQQEKPEGAETTAATTNGSLSDPSKEVEYVCELCKGAAPPDSPVVYSDRAGYNKQWHPTCFVCAKCSEPLVDLIY

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

>90743_90743_2_THRB-LMCD1_THRB_chr3_24184992_ENST00000280696_LMCD1_chr3_8574423_ENST00000535732_length(amino acids)=501AA_BP=265
MNQGNKMNYCMQEIYEVHPAAGSNCYMQSTDYYAYFEDSPGYSGCDAQAVPSNNIYMEQAWAVNQPYTCSYPGNMFKSKDSDLDMALNQY
SQPEYFTEEKPTFSQVQSPSYSQKKGYIPSYLDKDELCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRN
QCQECRFKKCIYVGMATDLVLDDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWKQKRKFLMSL
GQLQSARGVACLGCKGTCSGFEPHSWRKICKSCKCSQEDHCLTSDLEDDRKIGRLLMDSKYSTLTARVKGGDGIRIYKRNRMIMTNPIAT
GKDPTFDTITYEWAPPGVTQKLGLQYMELIPKEKQPVTGTEGAFYRRRQLMHQLPIYDQDPSRCRGLLENELKLMEEFVKQYKSEALGVG

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

>90743_90743_3_THRB-LMCD1_THRB_chr3_24184992_ENST00000356447_LMCD1_chr3_8574423_ENST00000157600_length(amino acids)=597AA_BP=244
MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQTTWTSSIFHLDHDDVNDQSVSSAQTFQTEE
KKCKGYIPSYLDKDELCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECRFKKCIYVGMATDLVL
DDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWKQKRKFLMSLGQLQSARGVACLGCKGTCSGF
EPHSWRKICKSCKCSQEDHCLTSDLEDDRKIGRLLMDSKYSTLTARVKGGDGIRIYKRNRMIMTNPIATGKDPTFDTITYEWAPPGVTQK
LGLQYMELIPKEKQPVTGTEGAFYRRRQLMHQLPIYDQDPSRCRGLLENELKLMEEFVKQYKSEALGVGEVALPGQGGLPKEEGKQQEKP
EGAETTAATTNGSLSDPSKEVEYVCELCKGAAPPDSPVVYSDRAGYNKQWHPTCFVCAKCSEPLVDLIYFWKDGAPWCGRHYCESLRPRC

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

>90743_90743_4_THRB-LMCD1_THRB_chr3_24184992_ENST00000356447_LMCD1_chr3_8574423_ENST00000535732_length(amino acids)=479AA_BP=244
MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQTTWTSSIFHLDHDDVNDQSVSSAQTFQTEE
KKCKGYIPSYLDKDELCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECRFKKCIYVGMATDLVL
DDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWKQKRKFLMSLGQLQSARGVACLGCKGTCSGF
EPHSWRKICKSCKCSQEDHCLTSDLEDDRKIGRLLMDSKYSTLTARVKGGDGIRIYKRNRMIMTNPIATGKDPTFDTITYEWAPPGVTQK
LGLQYMELIPKEKQPVTGTEGAFYRRRQLMHQLPIYDQDPSRCRGLLENELKLMEEFVKQYKSEALGVGEVALPGQGGLPKEEGKQQEKP

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

>90743_90743_5_THRB-LMCD1_THRB_chr3_24184992_ENST00000396671_LMCD1_chr3_8574423_ENST00000157600_length(amino acids)=597AA_BP=244
MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQTTWTSSIFHLDHDDVNDQSVSSAQTFQTEE
KKCKGYIPSYLDKDELCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECRFKKCIYVGMATDLVL
DDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWKQKRKFLMSLGQLQSARGVACLGCKGTCSGF
EPHSWRKICKSCKCSQEDHCLTSDLEDDRKIGRLLMDSKYSTLTARVKGGDGIRIYKRNRMIMTNPIATGKDPTFDTITYEWAPPGVTQK
LGLQYMELIPKEKQPVTGTEGAFYRRRQLMHQLPIYDQDPSRCRGLLENELKLMEEFVKQYKSEALGVGEVALPGQGGLPKEEGKQQEKP
EGAETTAATTNGSLSDPSKEVEYVCELCKGAAPPDSPVVYSDRAGYNKQWHPTCFVCAKCSEPLVDLIYFWKDGAPWCGRHYCESLRPRC

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

>90743_90743_6_THRB-LMCD1_THRB_chr3_24184992_ENST00000396671_LMCD1_chr3_8574423_ENST00000535732_length(amino acids)=480AA_BP=244
MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQTTWTSSIFHLDHDDVNDQSVSSAQTFQTEE
KKCKGYIPSYLDKDELCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECRFKKCIYVGMATDLVL
DDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWKQKRKFLMSLGQLQSARGVACLGCKGTCSGF
EPHSWRKICKSCKCSQEDHCLTSDLEDDRKIGRLLMDSKYSTLTARVKGGDGIRIYKRNRMIMTNPIATGKDPTFDTITYEWAPPGVTQK
LGLQYMELIPKEKQPVTGTEGAFYRRRQLMHQLPIYDQDPSRCRGLLENELKLMEEFVKQYKSEALGVGEVALPGQGGLPKEEGKQQEKP

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

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Fusion Protein Functional Features


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/chr3:24184992/chr3:8574423)
- 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
.LMCD1

Q9NZU5

FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.FUNCTION: Transcriptional cofactor that restricts GATA6 function by inhibiting DNA-binding, resulting in repression of GATA6 transcriptional activation of downstream target genes. Represses GATA6-mediated trans activation of lung- and cardiac tissue-specific promoters. Inhibits DNA-binding by GATA4 and GATA1 to the cTNC promoter (By similarity). Plays a critical role in the development of cardiac hypertrophy via activation of calcineurin/nuclear factor of activated T-cells signaling pathway. {ECO:0000250, ECO:0000269|PubMed:20026769}.

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.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneTHRBchr3:24184992chr3:8574423ENST00000280696-47107_181261.0477.0DNA bindingNuclear receptor
HgeneTHRBchr3:24184992chr3:8574423ENST00000356447-710107_181246.0462.0DNA bindingNuclear receptor
HgeneTHRBchr3:24184992chr3:8574423ENST00000396671-811107_181246.0462.0DNA bindingNuclear receptor
HgeneTHRBchr3:24184992chr3:8574423ENST00000416420-912107_181246.0462.0DNA bindingNuclear receptor
HgeneTHRBchr3:24184992chr3:8574423ENST00000280696-471_106261.0477.0RegionNote=Modulating
HgeneTHRBchr3:24184992chr3:8574423ENST00000356447-7101_106246.0462.0RegionNote=Modulating
HgeneTHRBchr3:24184992chr3:8574423ENST00000396671-8111_106246.0462.0RegionNote=Modulating
HgeneTHRBchr3:24184992chr3:8574423ENST00000416420-9121_106246.0462.0RegionNote=Modulating
HgeneTHRBchr3:24184992chr3:8574423ENST00000280696-47107_127261.0477.0Zinc fingerNR C4-type
HgeneTHRBchr3:24184992chr3:8574423ENST00000280696-47145_169261.0477.0Zinc fingerNR C4-type
HgeneTHRBchr3:24184992chr3:8574423ENST00000356447-710107_127246.0462.0Zinc fingerNR C4-type
HgeneTHRBchr3:24184992chr3:8574423ENST00000356447-710145_169246.0462.0Zinc fingerNR C4-type
HgeneTHRBchr3:24184992chr3:8574423ENST00000396671-811107_127246.0462.0Zinc fingerNR C4-type
HgeneTHRBchr3:24184992chr3:8574423ENST00000396671-811145_169246.0462.0Zinc fingerNR C4-type
HgeneTHRBchr3:24184992chr3:8574423ENST00000416420-912107_127246.0462.0Zinc fingerNR C4-type
HgeneTHRBchr3:24184992chr3:8574423ENST00000416420-912145_169246.0462.0Zinc fingerNR C4-type
TgeneLMCD1chr3:24184992chr3:8574423ENST000001576000628_5814.0366.0Compositional biasNote=Cys-rich
TgeneLMCD1chr3:24184992chr3:8574423ENST0000015760006241_30614.0366.0DomainLIM zinc-binding 1
TgeneLMCD1chr3:24184992chr3:8574423ENST0000015760006307_36514.0366.0DomainLIM zinc-binding 2
TgeneLMCD1chr3:24184992chr3:8574423ENST000001576000699_20614.0366.0DomainPET

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneTHRBchr3:24184992chr3:8574423ENST00000280696-47217_461261.0477.0DomainNR LBD
HgeneTHRBchr3:24184992chr3:8574423ENST00000356447-710217_461246.0462.0DomainNR LBD
HgeneTHRBchr3:24184992chr3:8574423ENST00000396671-811217_461246.0462.0DomainNR LBD
HgeneTHRBchr3:24184992chr3:8574423ENST00000416420-912217_461246.0462.0DomainNR LBD


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Fusion Protein-Protein Interaction


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 from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
THRB
LMCD1


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with
HgeneTHRBchr3:24184992chr3:8574423ENST00000280696-47244_461261.0477.0NR2F6
HgeneTHRBchr3:24184992chr3:8574423ENST00000356447-710244_461246.0462.0NR2F6
HgeneTHRBchr3:24184992chr3:8574423ENST00000396671-811244_461246.0462.0NR2F6
HgeneTHRBchr3:24184992chr3:8574423ENST00000416420-912244_461246.0462.0NR2F6


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Related Drugs to THRB-LMCD1


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to THRB-LMCD1


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

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