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Fusion Protein:NPHP4-CDKN2A |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: NPHP4-CDKN2A | FusionPDB ID: 59904 | FusionGDB2.0 ID: 59904 | Hgene | Tgene | Gene symbol | NPHP4 | CDKN2A | Gene ID | 261734 | 1029 |
| Gene name | nephrocystin 4 | cyclin dependent kinase inhibitor 2A | |
| Synonyms | POC10|SLSN4 | ARF|CDK4I|CDKN2|CMM2|INK4|INK4A|MLM|MTS-1|MTS1|P14|P14ARF|P16|P16-INK4A|P16INK4|P16INK4A|P19|P19ARF|TP16 | |
| Cytomap | 1p36.31 | 9p21.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | nephrocystin-4POC10 centriolar protein homolognephroretinin | cyclin-dependent kinase inhibitor 2ACDK4 inhibitor p16-INK4alternative reading framecell cycle negative regulator betacyclin-dependent kinase 4 inhibitor Acyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)multiple tumor suppressor 1 | |
| Modification date | 20200320 | 20200329 | |
| UniProtAcc | O75161 | Q96HQ2 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000378156, ENST00000478423, | ENST00000446177, ENST00000479692, ENST00000494262, ENST00000497750, ENST00000498124, ENST00000498628, ENST00000530628, ENST00000578845, ENST00000470819, ENST00000361570, ENST00000579755, ENST00000304494, ENST00000579122, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 7 X 10 X 5=350 | 13 X 5 X 10=650 |
| # samples | 10 | 16 | |
| ** MAII score | log2(10/350*10)=-1.8073549220576 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(16/650*10)=-2.02236781302845 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: NPHP4 [Title/Abstract] AND CDKN2A [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NPHP4(6046215)-CDKN2A(21971207), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | NPHP4-CDKN2A 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. NPHP4-CDKN2A 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. NPHP4-CDKN2A seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. NPHP4-CDKN2A 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) |
| Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Hgene | NPHP4 | GO:0090090 | negative regulation of canonical Wnt signaling pathway | 22654112 |
| Tgene | CDKN2A | GO:0000082 | G1/S transition of mitotic cell cycle | 10208428 |
| Tgene | CDKN2A | GO:0007050 | cell cycle arrest | 15149599 |
| Tgene | CDKN2A | GO:0008285 | negative regulation of cell proliferation | 15149599 |
| Tgene | CDKN2A | GO:0030308 | negative regulation of cell growth | 10208428 |
| Tgene | CDKN2A | GO:0032088 | negative regulation of NF-kappaB transcription factor activity | 10353611 |
| Tgene | CDKN2A | GO:0042326 | negative regulation of phosphorylation | 8259215|10208428 |
| Tgene | CDKN2A | GO:0045736 | negative regulation of cyclin-dependent protein serine/threonine kinase activity | 7739547|8259215 |
| Fusion gene breakpoints across NPHP4 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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| Fusion gene breakpoints across CDKN2A (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Fusion Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| 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. |
| Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | SKCM | TCGA-EE-A20H-06A | NPHP4 | chr1 | 6046215 | - | CDKN2A | chr9 | 21971207 | - |
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Fusion ORF Analysis |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| ENST00000378156 | NPHP4 | chr1 | 6046215 | - | ENST00000304494 | CDKN2A | chr9 | 21971207 | - | 1198 | 401 | 711 | 253 | 152 |
| ENST00000378156 | NPHP4 | chr1 | 6046215 | - | ENST00000579122 | CDKN2A | chr9 | 21971207 | - | 886 | 401 | 637 | 224 | 137 |
| DeepORF 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. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000378156 | ENST00000304494 | NPHP4 | chr1 | 6046215 | - | CDKN2A | chr9 | 21971207 | - | 0.13914774 | 0.86085224 |
| ENST00000378156 | ENST00000579122 | NPHP4 | chr1 | 6046215 | - | CDKN2A | chr9 | 21971207 | - | 0.32081422 | 0.6791858 |
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Fusion Amino Acid Sequences |
| 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 >59904_59904_1_NPHP4-CDKN2A_NPHP4_chr1_6046215_ENST00000378156_CDKN2A_chr9_21971207_ENST00000304494_length(amino acids)=152AA_BP=2 MSEGPSAASMRAWLLPLVPPAAARRYRATSRWPSSSARSTGRRPQASRTSSRAPARCSTTSVSRKPSRAASCTGRVRVAGSAQLGSAPWS -------------------------------------------------------------- >59904_59904_2_NPHP4-CDKN2A_NPHP4_chr1_6046215_ENST00000378156_CDKN2A_chr9_21971207_ENST00000579122_length(amino acids)=137AA_BP=2 MSCDIAMAQLLSQVHGQTAPGIAHVQPRPGPVQHHQRVQEALPGSVVHGSGESGGVGAVGLRAVEQQQLRHSGAAHHHDLPNYRSVQPLE -------------------------------------------------------------- |
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Fusion Protein Functional Features |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:6046215/chr9:21971207) - 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. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| NPHP4 | CDKN2A |
| FUNCTION: Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module (PubMed:19755384, PubMed:21565611). Does not seem to be strictly required for ciliogenesis (PubMed:21565611). Required for building functional cilia. Involved in the organization of the subapical actin network in multiciliated epithelial cells. Seems to recruit INT to basal bodies of motile cilia which subsequently interacts with actin-modifying proteins such as DAAM1 (By similarity). In cooperation with INVS may downregulate the canonical Wnt pathway and promote the Wnt-PCP pathway by regulating expression and subcellular location of disheveled proteins. Stabilizes protein levels of JADE1 and promotes its translocation to the nucleus leading to cooperative inhibition of canonical Wnt signaling (PubMed:21498478, PubMed:22654112). Acts as negative regulator of the hippo pathway by association with LATS1 and modifying LATS1-dependent phosphorylation and localization of WWTR1/TAZ (PubMed:21555462). {ECO:0000250|UniProtKB:B0DOB4, ECO:0000250|UniProtKB:P59240, ECO:0000269|PubMed:21498478, ECO:0000269|PubMed:21555462, ECO:0000269|PubMed:21565611, ECO:0000269|PubMed:22654112, ECO:0000305|PubMed:19755384}. |
| Retention 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 * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000304494 | 0 | 3 | 110_139 | 50.0 | 157.0 | Repeat | Note=ANK 4 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000304494 | 0 | 3 | 77_106 | 50.0 | 157.0 | Repeat | Note=ANK 3 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000446177 | 0 | 3 | 110_139 | 50.0 | 168.0 | Repeat | Note=ANK 4 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000446177 | 0 | 3 | 77_106 | 50.0 | 168.0 | Repeat | Note=ANK 3 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000494262 | 1 | 4 | 110_139 | 0 | 106.0 | Repeat | Note=ANK 4 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000494262 | 1 | 4 | 11_40 | 0 | 106.0 | Repeat | Note=ANK 1 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000494262 | 1 | 4 | 44_72 | 0 | 106.0 | Repeat | Note=ANK 2 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000494262 | 1 | 4 | 77_106 | 0 | 106.0 | Repeat | Note=ANK 3 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000498124 | 0 | 4 | 110_139 | 50.0 | 130.66666666666666 | Repeat | Note=ANK 4 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000498124 | 0 | 4 | 77_106 | 50.0 | 130.66666666666666 | Repeat | Note=ANK 3 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000498628 | 0 | 3 | 110_139 | 0 | 106.0 | Repeat | Note=ANK 4 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000498628 | 0 | 3 | 11_40 | 0 | 106.0 | Repeat | Note=ANK 1 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000498628 | 0 | 3 | 44_72 | 0 | 106.0 | Repeat | Note=ANK 2 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000498628 | 0 | 3 | 77_106 | 0 | 106.0 | Repeat | Note=ANK 3 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000578845 | 0 | 2 | 110_139 | 0 | 106.0 | Repeat | Note=ANK 4 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000578845 | 0 | 2 | 11_40 | 0 | 106.0 | Repeat | Note=ANK 1 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000578845 | 0 | 2 | 44_72 | 0 | 106.0 | Repeat | Note=ANK 2 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000578845 | 0 | 2 | 77_106 | 0 | 106.0 | Repeat | Note=ANK 3 |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | NPHP4 | chr1:6046215 | chr9:21971207 | ENST00000378156 | - | 2 | 30 | 823_1426 | 45.0 | 1427.0 | Region | Sufficient for basal bodies localization |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000304494 | 0 | 3 | 11_40 | 50.0 | 157.0 | Repeat | Note=ANK 1 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000304494 | 0 | 3 | 44_72 | 50.0 | 157.0 | Repeat | Note=ANK 2 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000446177 | 0 | 3 | 11_40 | 50.0 | 168.0 | Repeat | Note=ANK 1 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000446177 | 0 | 3 | 44_72 | 50.0 | 168.0 | Repeat | Note=ANK 2 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000498124 | 0 | 4 | 11_40 | 50.0 | 130.66666666666666 | Repeat | Note=ANK 1 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000498124 | 0 | 4 | 44_72 | 50.0 | 130.66666666666666 | Repeat | Note=ANK 2 |
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Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| NPHP4 | |
| CDKN2A |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000361570 | 0 | 3 | 1_64 | 105.33333333333333 | 220.0 | CDK5RAP3 and MDM2 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000530628 | 0 | 3 | 1_64 | 64.33333333333333 | 122.66666666666667 | CDK5RAP3 and MDM2 | |
| Tgene | CDKN2A | chr1:6046215 | chr9:21971207 | ENST00000579755 | 0 | 3 | 1_64 | 64.33333333333333 | 134.33333333333334 | CDK5RAP3 and MDM2 |
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Related Drugs to NPHP4-CDKN2A |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to NPHP4-CDKN2A |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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