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Center for Computational Systems Medicine level2
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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 Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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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:TMPRSS2-GRHL2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TMPRSS2-GRHL2
FusionPDB ID: 92382
FusionGDB2.0 ID: 92382
HgeneTgene
Gene symbol

TMPRSS2

GRHL2

Gene ID

7113

79977

Gene nametransmembrane serine protease 2grainyhead like transcription factor 2
SynonymsPP9284|PRSS10BOM|DFNA28|ECTDS|PPCD4|TFCP2L3
Cytomap

21q22.3

8q22.3

Type of geneprotein-codingprotein-coding
Descriptiontransmembrane protease serine 2epitheliasinserine protease 10transmembrane protease, serine 2grainyhead-like protein 2 homologbrother of mammalian grainyheadgrainyhead-like 2transcription factor CP2-like 3
Modification date2020031320200313
UniProtAcc

O15393

Q6ISB3

Ensembl transtripts involved in fusion geneENST idsENST00000332149, ENST00000398585, 
ENST00000458356, ENST00000497881, 
ENST00000517674, ENST00000251808, 
ENST00000395927, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score40 X 73 X 10=292008 X 8 X 5=320
# samples 1308
** MAII scorelog2(130/29200*10)=-4.48938484073892
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(8/320*10)=-2
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: TMPRSS2 [Title/Abstract] AND GRHL2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TMPRSS2(42861433)-GRHL2(102564942), # samples:3
TMPRSS2(42860320)-GRHL2(102564942), # samples:3
Anticipated loss of major functional domain due to fusion event.TMPRSS2-GRHL2 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.
TMPRSS2-GRHL2 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.
TMPRSS2-GRHL2 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.
TMPRSS2-GRHL2 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.
TMPRSS2-GRHL2 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
TMPRSS2-GRHL2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
TMPRSS2-GRHL2 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
TMPRSS2-GRHL2 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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
HgeneTMPRSS2

GO:0006508

proteolysis

21068237|24227843

HgeneTMPRSS2

GO:0046598

positive regulation of viral entry into host cell

21068237|24227843

TgeneGRHL2

GO:0008544

epidermis development

23254293

TgeneGRHL2

GO:0044030

regulation of DNA methylation

23254293

TgeneGRHL2

GO:0045617

negative regulation of keratinocyte differentiation

23254293

TgeneGRHL2

GO:0045944

positive regulation of transcription by RNA polymerase II

23814079


check buttonFusion gene breakpoints across TMPRSS2 (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 GRHL2 (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
ChimerDB4PRADTCGA-EJ-7314-01ATMPRSS2chr21

42860320

-GRHL2chr8

102564942

+
ChimerDB4PRADTCGA-EJ-7314-01ATMPRSS2chr21

42861433

-GRHL2chr8

102564942

+
ChimerDB4PRADTCGA-EJ-7314TMPRSS2chr21

42860320

-GRHL2chr8

102564942

+
ChimerDB4PRADTCGA-EJ-7314TMPRSS2chr21

42860321

-GRHL2chr8

102564943

+
ChimerDB4PRADTCGA-EJ-7314TMPRSS2chr21

42861433

-GRHL2chr8

102564942

+
ChimerDB4PRADTCGA-EJ-7314TMPRSS2chr21

42861434

-GRHL2chr8

102564943

+


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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)
ENST00000458356TMPRSS2chr2142861433-ENST00000251808GRHL2chr8102564942+50994143812075564
ENST00000458356TMPRSS2chr2142861433-ENST00000395927GRHL2chr8102564942+22664143812075564
ENST00000458356TMPRSS2chr2142860320-ENST00000251808GRHL2chr8102564942+52195344892195568
ENST00000458356TMPRSS2chr2142860320-ENST00000395927GRHL2chr8102564942+23865344892195568
ENST00000458356TMPRSS2chr2142861434-ENST00000251808GRHL2chr8102564943+50994143812075564
ENST00000458356TMPRSS2chr2142861434-ENST00000395927GRHL2chr8102564943+22664143812075564
ENST00000458356TMPRSS2chr2142860321-ENST00000251808GRHL2chr8102564943+52195344892195568
ENST00000458356TMPRSS2chr2142860321-ENST00000395927GRHL2chr8102564943+23865344892195568

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
ENST00000458356ENST00000251808TMPRSS2chr2142861433-GRHL2chr8102564942+0.0013152860.9986847
ENST00000458356ENST00000395927TMPRSS2chr2142861433-GRHL2chr8102564942+0.0045215030.9954786
ENST00000458356ENST00000251808TMPRSS2chr2142860320-GRHL2chr8102564942+0.0020737260.99792624
ENST00000458356ENST00000395927TMPRSS2chr2142860320-GRHL2chr8102564942+0.0066037860.9933962
ENST00000458356ENST00000251808TMPRSS2chr2142861434-GRHL2chr8102564943+0.0013152860.9986847
ENST00000458356ENST00000395927TMPRSS2chr2142861434-GRHL2chr8102564943+0.0045215030.9954786
ENST00000458356ENST00000251808TMPRSS2chr2142860321-GRHL2chr8102564943+0.0020737260.99792624
ENST00000458356ENST00000395927TMPRSS2chr2142860321-GRHL2chr8102564943+0.0066037860.9933962

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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

>92382_92382_1_TMPRSS2-GRHL2_TMPRSS2_chr21_42860320_ENST00000458356_GRHL2_chr8_102564942_ENST00000251808_length(amino acids)=568AA_BP=15
MACHTAPAGRTRIGVVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESS
AIIPVSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEE
YMYDQTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTA
KQRVLDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFC
DKGAERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGG
SVLVKRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNI

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

>92382_92382_2_TMPRSS2-GRHL2_TMPRSS2_chr21_42860320_ENST00000458356_GRHL2_chr8_102564942_ENST00000395927_length(amino acids)=568AA_BP=15
MACHTAPAGRTRIGVVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESS
AIIPVSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEE
YMYDQTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTA
KQRVLDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFC
DKGAERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGG
SVLVKRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNI

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

>92382_92382_3_TMPRSS2-GRHL2_TMPRSS2_chr21_42860321_ENST00000458356_GRHL2_chr8_102564943_ENST00000251808_length(amino acids)=568AA_BP=15
MACHTAPAGRTRIGVVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESS
AIIPVSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEE
YMYDQTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTA
KQRVLDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFC
DKGAERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGG
SVLVKRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNI

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

>92382_92382_4_TMPRSS2-GRHL2_TMPRSS2_chr21_42860321_ENST00000458356_GRHL2_chr8_102564943_ENST00000395927_length(amino acids)=568AA_BP=15
MACHTAPAGRTRIGVVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESS
AIIPVSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEE
YMYDQTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTA
KQRVLDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFC
DKGAERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGG
SVLVKRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNI

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

>92382_92382_5_TMPRSS2-GRHL2_TMPRSS2_chr21_42861433_ENST00000458356_GRHL2_chr8_102564942_ENST00000251808_length(amino acids)=564AA_BP=11
MRWPLAYSGSSVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESSAIIP
VSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEEYMYD
QTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTAKQRV
LDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFCDKGA
ERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGGSVLV
KRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNIIEHY

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

>92382_92382_6_TMPRSS2-GRHL2_TMPRSS2_chr21_42861433_ENST00000458356_GRHL2_chr8_102564942_ENST00000395927_length(amino acids)=564AA_BP=11
MRWPLAYSGSSVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESSAIIP
VSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEEYMYD
QTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTAKQRV
LDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFCDKGA
ERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGGSVLV
KRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNIIEHY

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

>92382_92382_7_TMPRSS2-GRHL2_TMPRSS2_chr21_42861434_ENST00000458356_GRHL2_chr8_102564943_ENST00000251808_length(amino acids)=564AA_BP=11
MRWPLAYSGSSVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESSAIIP
VSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEEYMYD
QTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTAKQRV
LDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFCDKGA
ERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGGSVLV
KRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNIIEHY

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

>92382_92382_8_TMPRSS2-GRHL2_TMPRSS2_chr21_42861434_ENST00000458356_GRHL2_chr8_102564943_ENST00000395927_length(amino acids)=564AA_BP=11
MRWPLAYSGSSVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESSAIIP
VSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEEYMYD
QTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTAKQRV
LDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFCDKGA
ERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGGSVLV
KRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNIIEHY

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

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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/chr21:42861433/chr8:102564942)
- 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
TMPRSS2

O15393

GRHL2

Q6ISB3

FUNCTION: Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:26018085, PubMed:25122198). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity). {ECO:0000250|UniProtKB:Q9JIQ8, ECO:0000269|PubMed:15537383, ECO:0000269|PubMed:25122198, ECO:0000269|PubMed:26018085}.; FUNCTION: (Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via two independent mechanisms, proteolytic cleavage of ACE2 receptor which promotes viral uptake, and cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651, PubMed:32404436, PubMed:34159616, PubMed:33051876). Upon SARS-CoV-2 infection, increases syncytia formation by accelerating the fusion process (PubMed:34159616, PubMed:33051876). Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity. {ECO:0000269|PubMed:21068237, ECO:0000269|PubMed:21325420, ECO:0000269|PubMed:23536651, ECO:0000269|PubMed:23966399, ECO:0000269|PubMed:24027332, ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32404436, ECO:0000269|PubMed:33051876, ECO:0000269|PubMed:34159616}.FUNCTION: Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:29309642, PubMed:25152456). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5'-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293). {ECO:0000250|UniProtKB:Q8K5C0, ECO:0000269|PubMed:19015635, ECO:0000269|PubMed:20938050, ECO:0000269|PubMed:20978075, ECO:0000269|PubMed:23254293, ECO:0000269|PubMed:25152456, ECO:0000269|PubMed:29309642, ECO:0000305|PubMed:12175488}.

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
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000332149-514112_149148.33333333333334493.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000398585-514112_149185.33333333333334530.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000458356-514112_149148.33333333333334493.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000332149-514112_149148.33333333333334493.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000398585-514112_149185.33333333333334530.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000458356-514112_149148.33333333333334493.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000332149-5141_84148.33333333333334493.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000398585-5141_84185.33333333333334530.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000458356-5141_84148.33333333333334493.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000332149-5141_84148.33333333333334493.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000398585-5141_84185.33333333333334530.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000458356-5141_84148.33333333333334493.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000332149-4141_84108.33333333333333493.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000398585-4141_84145.33333333333334530.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000458356-4141_84108.33333333333333493.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000332149-4141_84108.33333333333333493.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000398585-4141_84145.33333333333334530.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000458356-4141_84108.33333333333333493.0Topological domainCytoplasmic
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000332149-51485_105148.33333333333334493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000398585-51485_105185.33333333333334530.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000458356-51485_105148.33333333333334493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000332149-51485_105148.33333333333334493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000398585-51485_105185.33333333333334530.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000458356-51485_105148.33333333333334493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000332149-41485_105108.33333333333333493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000398585-41485_105145.33333333333334530.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000458356-41485_105108.33333333333333493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000332149-41485_105108.33333333333333493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000398585-41485_105145.33333333333334530.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000458356-41485_105108.33333333333333493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000332149-514150_242148.33333333333334493.0DomainSRCR
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000332149-514256_489148.33333333333334493.0DomainPeptidase S1
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000398585-514150_242185.33333333333334530.0DomainSRCR
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000398585-514256_489185.33333333333334530.0DomainPeptidase S1
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000458356-514150_242148.33333333333334493.0DomainSRCR
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000458356-514256_489148.33333333333334493.0DomainPeptidase S1
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000332149-514150_242148.33333333333334493.0DomainSRCR
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000332149-514256_489148.33333333333334493.0DomainPeptidase S1
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000398585-514150_242185.33333333333334530.0DomainSRCR
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000398585-514256_489185.33333333333334530.0DomainPeptidase S1
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000458356-514150_242148.33333333333334493.0DomainSRCR
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000458356-514256_489148.33333333333334493.0DomainPeptidase S1
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000332149-414112_149108.33333333333333493.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000332149-414150_242108.33333333333333493.0DomainSRCR
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000332149-414256_489108.33333333333333493.0DomainPeptidase S1
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000398585-414112_149145.33333333333334530.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000398585-414150_242145.33333333333334530.0DomainSRCR
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000398585-414256_489145.33333333333334530.0DomainPeptidase S1
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000458356-414112_149108.33333333333333493.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000458356-414150_242108.33333333333333493.0DomainSRCR
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000458356-414256_489108.33333333333333493.0DomainPeptidase S1
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000332149-414112_149108.33333333333333493.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000332149-414150_242108.33333333333333493.0DomainSRCR
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000332149-414256_489108.33333333333333493.0DomainPeptidase S1
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000398585-414112_149145.33333333333334530.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000398585-414150_242145.33333333333334530.0DomainSRCR
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000398585-414256_489145.33333333333334530.0DomainPeptidase S1
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000458356-414112_149108.33333333333333493.0DomainLDL-receptor class A
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000458356-414150_242108.33333333333333493.0DomainSRCR
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000458356-414256_489108.33333333333333493.0DomainPeptidase S1
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000332149-514106_492148.33333333333334493.0Topological domainExtracellular
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000398585-514106_492185.33333333333334530.0Topological domainExtracellular
HgeneTMPRSS2chr21:42860320chr8:102564942ENST00000458356-514106_492148.33333333333334493.0Topological domainExtracellular
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000332149-514106_492148.33333333333334493.0Topological domainExtracellular
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000398585-514106_492185.33333333333334530.0Topological domainExtracellular
HgeneTMPRSS2chr21:42860321chr8:102564943ENST00000458356-514106_492148.33333333333334493.0Topological domainExtracellular
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000332149-414106_492108.33333333333333493.0Topological domainExtracellular
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000398585-414106_492145.33333333333334530.0Topological domainExtracellular
HgeneTMPRSS2chr21:42861433chr8:102564942ENST00000458356-414106_492108.33333333333333493.0Topological domainExtracellular
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000332149-414106_492108.33333333333333493.0Topological domainExtracellular
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000398585-414106_492145.33333333333334530.0Topological domainExtracellular
HgeneTMPRSS2chr21:42861434chr8:102564943ENST00000458356-414106_492108.33333333333333493.0Topological domainExtracellular
TgeneGRHL2chr21:42860320chr8:102564942ENST000002518081161_9372.0626.0RegionTranscription activation
TgeneGRHL2chr21:42860320chr8:102564942ENST000003959271161_9356.0610.0RegionTranscription activation
TgeneGRHL2chr21:42860321chr8:102564943ENST000002518081161_9372.0626.0RegionTranscription activation
TgeneGRHL2chr21:42860321chr8:102564943ENST000003959271161_9356.0610.0RegionTranscription activation
TgeneGRHL2chr21:42861433chr8:102564942ENST000002518081161_9372.0626.0RegionTranscription activation
TgeneGRHL2chr21:42861433chr8:102564942ENST000003959271161_9356.0610.0RegionTranscription activation
TgeneGRHL2chr21:42861434chr8:102564943ENST000002518081161_9372.0626.0RegionTranscription activation
TgeneGRHL2chr21:42861434chr8:102564943ENST000003959271161_9356.0610.0RegionTranscription activation


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Fusion Protein Structures

check button 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)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file >>>1209_TMPRSS2_42861433_GRHL2_102564942_1209_TMPRSS2_42861433_GRHL2_102564942_ranked_0.pdbTMPRSS24286032142861433ENST00000395927GRHL2chr8102564942+
MRWPLAYSGSSVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESSAIIP
VSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEEYMYD
QTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTAKQRV
LDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFCDKGA
ERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGGSVLV
KRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNIIEHY
564


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pLDDT score distribution

check button 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.
TMPRSS2_pLDDT.png
all structure
all structure
GRHL2_pLDDT.png
all structure
all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
all structure


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Ramachandran Plot of Fusion Protein Structure


check button 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


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
TMPRSS2CLK1, HNRNPL, DCAF4, S, ACE2, STX7, SCD, PLP2, PLLP, MOSPD3, UPK2, SELK, C3orf52, IGFBP5, SEC22A, PLP1, CLN6, TMEM128, C14orf1, CFHR5, TMEM243, TMEM60, CXCL9, BNIP2, CNIH3, PGAP2, TMEM218, TMEM86A, CMTM7, ZFPL1, BMP10, TMEM79, SLC35A1, SFTPC, VAMP5, FAXDC2, STX8, NINJ2, CLEC7A, C2CD2L, CNIH2, BNIP3, DEFB103A, DEFB103B, TMEM11, C17orf62, TMEM86B, ADIPOQ, EDDM3B, BRICD5, PTTG1IP, PTCH1, ANKRD46, TMEM222, C1QL4, TMEM120B, FAM3C, TMEM229B, PLN, CTXN3, TNF, SMIM1, AQP1, TMPRSS2, DNASE2, MYO1C, PGRMC1, NDUFA4, ADAM10, CLGN, SEC16A, SPINT2, COCH, B4GAT1, XPOT, MYO1B, LANCL1, CALU, PLXNA2, GPC4, BANF1, CPD, CLPX, STC2, SLIT2, MYO1D, ERLIN2, BAG2, TFRC, HLA-A, TP53, RPN1, RPN2, GNAI2, APP, ITGB1, INSR, GLA, GPI, ITGAV, CTSD, APRT, IGF1R, MET, GNAI3, CLTA, CALM2, HLA-C, DLAT, HSPA5, LAMC1, LAMP1, IGF2R, PDIA4, P4HA1, HSP90B1, PVR, RPA2, ATP2A2, PFKL, CDH2, MSH3, RPA1, CALR, RPA3, LONP1, TGFBR1, DDOST, HADHA, ECE1, DNM2, FXR2, PLXNA3, ATP1B3, HADHB, SEC61A1, GNB1, NOMO3, PRKDC, TFAM, SLC7A5, PFKP, KIF23, FMR1, PTK7, ADAM15, CUL2, SCARB2, WRN, DSC3, ITIH4, GANAB, KARS, RCN1, SAFB, IMMT, HSD17B12, UBR4, QSOX2, RRM2B, MON2, YTHDF3, PABPN1, PLD3, PELP1, TTC13, CNNM3, IPO4, FAR1, GGH, ERLEC1, RBM33, DNAJA3, RBM14, PPP1R9B, SDF2, NEU1, GRWD1, AIF1L, NTPCR, FUCA2, EDEM3, RACGAP1, RAB18, TMEM106B, CHPF2, GNG12, DNAJB11, EGFL7, DDX20, ADAMTS1, LNPEP, ITM2B, MRPL11, HYOU1, AFG3L2, YTHDF2, SUPT16H, PDHX, IPO5, SAP18, HGS, SPTBN2, PLXNB2, ARPC3, ACTN4, TRIM13, PDCD6, MPDU1, SEC22B, ATP6AP2, STAM2, ARL6IP5, UFL1, SEC31A, STBD1, SMC2, SEC24A, SEC24B, ACSL3, CDK1, SRPR, SPTB, MTHFD1, ACTN1, ETFA, RAB6A, VDAC1, HMOX2, MYH10, DEK, ATP5C1, NAMPT, VDAC2, QARS, TUFM, SERPINH1, BCAP31, PSMD7, CLCN7, SLC25A1, YARS, EPPK1, RAB10, ABCE1, RHOA, CNBP, TPM4, SLC25A11, LMNB2, CKAP4, GOLGA3, TWF1, TRAP1, STX5, DDX39B, RAB3GAP1, PON2, PPA1, SEC23A, SEC23B, NDUFA9, ATP6V1F, INF2, ANO6, ACTBL2, MIA3, CDKAL1, KIAA0368, C19orf70, SLC25A24, HUWE1, MEGF8, KTN1, COMTD1, ANKLE2, VRK2, ZDHHC17, DNAH10, NUP93, MMGT1, TMEM199, ATPAF2, EMC1, PDZD8, NBEA, MOSPD2, PDCD6IP, SYNE2, UBXN4, CCDC47, LRRC59, C7orf55, DDRGK1, NGLY1, CDK5RAP3, CCDC115, CLCC1, OSBPL9, RBM15, CGRRF1, ESYT1, NDC1, EFHD1, OSBPL8, KIAA1715, LSG1, RAB1B, TMX1, GORASP2, SFXN1, XPO5, VEZT, JPH1, BIRC6, AAAS, TOMM22, DDX19A, SMPD4, TMOD3, EMC3, VAPA, CEP72, LARS, DPM3, DHCR7, UBA2, AASS, ATP6V1H, SLC25A13, STOML2, RAB21, MYO6, VDAC3, AUP1, SEC23IP,


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
TMPRSS2all structure
GRHL2


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 TMPRSS2-GRHL2


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 TMPRSS2-GRHL2


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
HgeneTMPRSS2C0033578Prostatic Neoplasms4CTD_human
HgeneTMPRSS2C0376358Malignant neoplasm of prostate4CTD_human