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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:NTN4-LETMD1

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NTN4-LETMD1
FusionPDB ID: 60680
FusionGDB2.0 ID: 60680
HgeneTgene
Gene symbol

NTN4

LETMD1

Gene ID

59277

25875

Gene namenetrin 4LETM1 domain containing 1
SynonymsPRO30911110019O13Rik|HCCR|HCCR-1|HCCR-2|HCCR1|HCCR2|HCRR-2|SLC55A3
Cytomap

12q22

12q13.12

Type of geneprotein-codingprotein-coding
Descriptionnetrin-4beta-netrinhepar-derived netrin-like proteinLETM1 domain-containing protein 1cervical cancer 1 proto-oncogene protein p40cervical cancer proto-oncogene 2 proteinepididymis secretory sperm binding proteinhuman cervical cancer oncogeneregulator of TP53
Modification date2020031320200322
UniProtAcc.

Q6P1Q0

Ensembl transtripts involved in fusion geneENST idsENST00000343702, ENST00000344911, 
ENST00000538383, ENST00000553059, 
ENST00000552603, 		ENST00000380123, 
ENST00000418425, ENST00000547008, 
ENST00000548516, ENST00000552739, 
ENST00000262055, ENST00000550929, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 10 X 5=5505 X 3 X 4=60
# samples 115
** MAII scorelog2(11/550*10)=-2.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(5/60*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: NTN4 [Title/Abstract] AND LETMD1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NTN4(96180717)-LETMD1(51450133), # samples:2
Anticipated loss of major functional domain due to fusion event.NTN4-LETMD1 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.
NTN4-LETMD1 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.
NTN4-LETMD1 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.
NTN4-LETMD1 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.
NTN4-LETMD1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NTN4-LETMD1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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 NTN4 (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 LETMD1 (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
ChimerDB4SARCTCGA-DX-AB2G-01ANTN4chr12

96180717

-LETMD1chr12

51450133

+


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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)
ENST00000343702NTN4chr1296180717-ENST00000550929LETMD1chr1251450133+172910341131354413
ENST00000343702NTN4chr1296180717-ENST00000262055LETMD1chr1251450133+234510341131354413
ENST00000344911NTN4chr1296180717-ENST00000550929LETMD1chr1251450133+126657143891282
ENST00000344911NTN4chr1296180717-ENST00000262055LETMD1chr1251450133+188257143891282
ENST00000553059NTN4chr1296180717-ENST00000550929LETMD1chr1251450133+12805850905301
ENST00000553059NTN4chr1296180717-ENST00000262055LETMD1chr1251450133+18965850905301

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
ENST00000343702ENST00000550929NTN4chr1296180717-LETMD1chr1251450133+0.034666680.9653334
ENST00000343702ENST00000262055NTN4chr1296180717-LETMD1chr1251450133+0.024121120.9758789
ENST00000344911ENST00000550929NTN4chr1296180717-LETMD1chr1251450133+0.0586184750.94138145
ENST00000344911ENST00000262055NTN4chr1296180717-LETMD1chr1251450133+0.031731070.968269
ENST00000553059ENST00000550929NTN4chr1296180717-LETMD1chr1251450133+0.036975860.9630242
ENST00000553059ENST00000262055NTN4chr1296180717-LETMD1chr1251450133+0.013420160.98657984

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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

>60680_60680_1_NTN4-LETMD1_NTN4_chr12_96180717_ENST00000343702_LETMD1_chr12_51450133_ENST00000262055_length(amino acids)=413AA_BP=307
MRAPSPGLAADEPAGPLRGAAQPGRLWSRGSRRPPGARDPPGRCARVTPPPRAVPAPGSQLPATADRARRPRRRKKPGPRSLPRTAALHP
AAQRSRLPPAPARPGCSRLLPAMGSCARLLLLWGCTVVAAGLSGVAGVSSRCEKACNPRMGNLALGRKLWADTTCGQNATELYCFYSENT
DLTCRQPKCDKCNAAYPHLAHLPSAMADSSFRFPRTWWQSAEDVHREKIQLDLEAEFYFTHLIVMFKSPRPAAMVLDRSQDFGKTWKPYK
YFATNCSATFGLEDDVVKKGAICTSKYSSPFPCTGGEKALSRAMLLTSYLPPPLLRHRLKTHTTVIHQLDKALAKLGIGQLTAQEVKSAC

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

>60680_60680_2_NTN4-LETMD1_NTN4_chr12_96180717_ENST00000343702_LETMD1_chr12_51450133_ENST00000550929_length(amino acids)=413AA_BP=307
MRAPSPGLAADEPAGPLRGAAQPGRLWSRGSRRPPGARDPPGRCARVTPPPRAVPAPGSQLPATADRARRPRRRKKPGPRSLPRTAALHP
AAQRSRLPPAPARPGCSRLLPAMGSCARLLLLWGCTVVAAGLSGVAGVSSRCEKACNPRMGNLALGRKLWADTTCGQNATELYCFYSENT
DLTCRQPKCDKCNAAYPHLAHLPSAMADSSFRFPRTWWQSAEDVHREKIQLDLEAEFYFTHLIVMFKSPRPAAMVLDRSQDFGKTWKPYK
YFATNCSATFGLEDDVVKKGAICTSKYSSPFPCTGGEKALSRAMLLTSYLPPPLLRHRLKTHTTVIHQLDKALAKLGIGQLTAQEVKSAC

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

>60680_60680_3_NTN4-LETMD1_NTN4_chr12_96180717_ENST00000344911_LETMD1_chr12_51450133_ENST00000262055_length(amino acids)=282AA_BP=176
MSGVAGVSSRCEKACNPRMGNLALGRKLWADTTCGQNATELYCFYSENTDLTCRQPKCDKCNAAYPHLAHLPSAMADSSFRFPRTWWQSA
EDVHREKIQLDLEAEFYFTHLIVMFKSPRPAAMVLDRSQDFGKTWKPYKYFATNCSATFGLEDDVVKKGAICTSKYSSPFPCTGGEKALS
RAMLLTSYLPPPLLRHRLKTHTTVIHQLDKALAKLGIGQLTAQEVKSACYLRGLNSTHIGEDRCRTWLGEWLQISCSLKEAELSLLLHNV

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

>60680_60680_4_NTN4-LETMD1_NTN4_chr12_96180717_ENST00000344911_LETMD1_chr12_51450133_ENST00000550929_length(amino acids)=282AA_BP=176
MSGVAGVSSRCEKACNPRMGNLALGRKLWADTTCGQNATELYCFYSENTDLTCRQPKCDKCNAAYPHLAHLPSAMADSSFRFPRTWWQSA
EDVHREKIQLDLEAEFYFTHLIVMFKSPRPAAMVLDRSQDFGKTWKPYKYFATNCSATFGLEDDVVKKGAICTSKYSSPFPCTGGEKALS
RAMLLTSYLPPPLLRHRLKTHTTVIHQLDKALAKLGIGQLTAQEVKSACYLRGLNSTHIGEDRCRTWLGEWLQISCSLKEAELSLLLHNV

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

>60680_60680_5_NTN4-LETMD1_NTN4_chr12_96180717_ENST00000553059_LETMD1_chr12_51450133_ENST00000262055_length(amino acids)=301AA_BP=195
MGSCARLLLLWGCTVVAAGLSGVAGVSSRCEKACNPRMGNLALGRKLWADTTCGQNATELYCFYSENTDLTCRQPKCDKCNAAYPHLAHL
PSAMADSSFRFPRTWWQSAEDVHREKIQLDLEAEFYFTHLIVMFKSPRPAAMVLDRSQDFGKTWKPYKYFATNCSATFGLEDDVVKKGAI
CTSKYSSPFPCTGGEKALSRAMLLTSYLPPPLLRHRLKTHTTVIHQLDKALAKLGIGQLTAQEVKSACYLRGLNSTHIGEDRCRTWLGEW

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

>60680_60680_6_NTN4-LETMD1_NTN4_chr12_96180717_ENST00000553059_LETMD1_chr12_51450133_ENST00000550929_length(amino acids)=301AA_BP=195
MGSCARLLLLWGCTVVAAGLSGVAGVSSRCEKACNPRMGNLALGRKLWADTTCGQNATELYCFYSENTDLTCRQPKCDKCNAAYPHLAHL
PSAMADSSFRFPRTWWQSAEDVHREKIQLDLEAEFYFTHLIVMFKSPRPAAMVLDRSQDFGKTWKPYKYFATNCSATFGLEDDVVKKGAI
CTSKYSSPFPCTGGEKALSRAMLLTSYLPPPLLRHRLKTHTTVIHQLDKALAKLGIGQLTAQEVKSACYLRGLNSTHIGEDRCRTWLGEW

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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/chr12:96180717/chr12:51450133)
- 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
.LETMD1

Q6P1Q0

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: Involved in tumorigenesis and may function as a negative regulator of the p53/TP53. {ECO:0000269|PubMed:12879013}.

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
TgeneLETMD1chr12:96180717chr12:51450133ENST0000038012337186_360187.66666666666666372.3333333333333DomainLetm1 RBD

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneNTN4chr12:96180717chr12:51450133ENST00000343702-210262_331195.0629.0DomainLaminin EGF-like 1
HgeneNTN4chr12:96180717chr12:51450133ENST00000343702-21030_261195.0629.0DomainLaminin N-terminal
HgeneNTN4chr12:96180717chr12:51450133ENST00000343702-210332_394195.0629.0DomainLaminin EGF-like 2
HgeneNTN4chr12:96180717chr12:51450133ENST00000343702-210395_448195.0629.0DomainLaminin EGF-like 3
HgeneNTN4chr12:96180717chr12:51450133ENST00000343702-210506_627195.0629.0DomainNTR
HgeneNTN4chr12:96180717chr12:51450133ENST00000344911-311262_331158.0592.0DomainLaminin EGF-like 1
HgeneNTN4chr12:96180717chr12:51450133ENST00000344911-31130_261158.0592.0DomainLaminin N-terminal
HgeneNTN4chr12:96180717chr12:51450133ENST00000344911-311332_394158.0592.0DomainLaminin EGF-like 2
HgeneNTN4chr12:96180717chr12:51450133ENST00000344911-311395_448158.0592.0DomainLaminin EGF-like 3
HgeneNTN4chr12:96180717chr12:51450133ENST00000344911-311506_627158.0592.0DomainNTR
HgeneNTN4chr12:96180717chr12:51450133ENST00000538383-210262_331158.0592.0DomainLaminin EGF-like 1
HgeneNTN4chr12:96180717chr12:51450133ENST00000538383-21030_261158.0592.0DomainLaminin N-terminal
HgeneNTN4chr12:96180717chr12:51450133ENST00000538383-210332_394158.0592.0DomainLaminin EGF-like 2
HgeneNTN4chr12:96180717chr12:51450133ENST00000538383-210395_448158.0592.0DomainLaminin EGF-like 3
HgeneNTN4chr12:96180717chr12:51450133ENST00000538383-210506_627158.0592.0DomainNTR
HgeneNTN4chr12:96180717chr12:51450133ENST00000553059-29262_331195.0606.0DomainLaminin EGF-like 1
HgeneNTN4chr12:96180717chr12:51450133ENST00000553059-2930_261195.0606.0DomainLaminin N-terminal
HgeneNTN4chr12:96180717chr12:51450133ENST00000553059-29332_394195.0606.0DomainLaminin EGF-like 2
HgeneNTN4chr12:96180717chr12:51450133ENST00000553059-29395_448195.0606.0DomainLaminin EGF-like 3
HgeneNTN4chr12:96180717chr12:51450133ENST00000553059-29506_627195.0606.0DomainNTR
TgeneLETMD1chr12:96180717chr12:51450133ENST0000026205559186_360254.0361.0DomainLetm1 RBD
TgeneLETMD1chr12:96180717chr12:51450133ENST0000041842559186_360267.0374.0DomainLetm1 RBD
TgeneLETMD1chr12:96180717chr12:51450133ENST0000055092959186_360198.0305.0DomainLetm1 RBD
TgeneLETMD1chr12:96180717chr12:51450133ENST00000262055591_110254.0361.0RegionNote=Required and sufficient for mitochondrial import
TgeneLETMD1chr12:96180717chr12:51450133ENST00000380123371_110187.66666666666666372.3333333333333RegionNote=Required and sufficient for mitochondrial import
TgeneLETMD1chr12:96180717chr12:51450133ENST00000418425591_110267.0374.0RegionNote=Required and sufficient for mitochondrial import
TgeneLETMD1chr12:96180717chr12:51450133ENST00000550929591_110198.0305.0RegionNote=Required and sufficient for mitochondrial import
TgeneLETMD1chr12:96180717chr12:51450133ENST0000026205559159_360254.0361.0Topological domainMitochondrial intermembrane
TgeneLETMD1chr12:96180717chr12:51450133ENST00000262055591_137254.0361.0Topological domainCytoplasmic
TgeneLETMD1chr12:96180717chr12:51450133ENST0000038012337159_360187.66666666666666372.3333333333333Topological domainMitochondrial intermembrane
TgeneLETMD1chr12:96180717chr12:51450133ENST00000380123371_137187.66666666666666372.3333333333333Topological domainCytoplasmic
TgeneLETMD1chr12:96180717chr12:51450133ENST0000041842559159_360267.0374.0Topological domainMitochondrial intermembrane
TgeneLETMD1chr12:96180717chr12:51450133ENST00000418425591_137267.0374.0Topological domainCytoplasmic
TgeneLETMD1chr12:96180717chr12:51450133ENST0000055092959159_360198.0305.0Topological domainMitochondrial intermembrane
TgeneLETMD1chr12:96180717chr12:51450133ENST00000550929591_137198.0305.0Topological domainCytoplasmic
TgeneLETMD1chr12:96180717chr12:51450133ENST0000026205559138_158254.0361.0TransmembraneHelical
TgeneLETMD1chr12:96180717chr12:51450133ENST0000038012337138_158187.66666666666666372.3333333333333TransmembraneHelical
TgeneLETMD1chr12:96180717chr12:51450133ENST0000041842559138_158267.0374.0TransmembraneHelical
TgeneLETMD1chr12:96180717chr12:51450133ENST0000055092959138_158198.0305.0TransmembraneHelical


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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
NTN4
LETMD1


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


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Related Drugs to NTN4-LETMD1


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 NTN4-LETMD1


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