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Fusion Protein:CDC73-FAM172A |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: CDC73-FAM172A | FusionPDB ID: 14942 | FusionGDB2.0 ID: 14942 | Hgene | Tgene | Gene symbol | CDC73 | FAM172A | Gene ID | 79577 | 83989 |
| Gene name | cell division cycle 73 | family with sequence similarity 172 member A | |
| Synonyms | C1orf28|FIHP|HPTJT|HRPT1|HRPT2|HYX | C5orf21|Toupee | |
| Cytomap | 1q31.2 | 5q15 | |
| Type of gene | protein-coding | protein-coding | |
| Description | parafibrominFamilial isolated hyperparathyroidismPaf1/RNA polymerase II complex componentcell division cycle 73 Paf1/RNA polymerase II complex component-like proteincell division cycle 73, Paf1/RNA polymerase II complex component, homologcell divisio | cotranscriptional regulator FAM172Aprotein FAM172A | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | Q6P1J9 | Q8WUF8 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000367435, ENST00000477868, | ENST00000504768, ENST00000395965, ENST00000505869, ENST00000509739, ENST00000509163, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 8 X 6 X 6=288 | 11 X 14 X 6=924 |
| # samples | 8 | 23 | |
| ** MAII score | log2(8/288*10)=-1.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(23/924*10)=-2.00625899047168 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: CDC73 [Title/Abstract] AND FAM172A [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CDC73(193121574)-FAM172A(92956835), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | CDC73-FAM172A 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. CDC73-FAM172A 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. CDC73-FAM172A 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. CDC73-FAM172A 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. CDC73-FAM172A seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. CDC73-FAM172A seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. CDC73-FAM172A seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. CDC73-FAM172A seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. CDC73-FAM172A 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 | CDC73 | GO:0008285 | negative regulation of cell proliferation | 16989776 |
| Hgene | CDC73 | GO:0010390 | histone monoubiquitination | 16307923 |
| Hgene | CDC73 | GO:0030177 | positive regulation of Wnt signaling pathway | 16630820 |
| Hgene | CDC73 | GO:0032968 | positive regulation of transcription elongation from RNA polymerase II promoter | 20178742 |
| Hgene | CDC73 | GO:0033523 | histone H2B ubiquitination | 16307923 |
| Hgene | CDC73 | GO:0045638 | negative regulation of myeloid cell differentiation | 20541477 |
| Hgene | CDC73 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 20178742 |
| Hgene | CDC73 | GO:2000134 | negative regulation of G1/S transition of mitotic cell cycle | 16989776 |
| Fusion gene breakpoints across CDC73 (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 FAM172A (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 | LAML | TCGA-AB-2939-03A | CDC73 | chr1 | 193121574 | - | FAM172A | chr5 | 92956835 | - |
| ChimerDB4 | LAML | TCGA-AB-2939_61FFWAAXX_7 | CDC73 | chr1 | 193121574 | + | FAM172A | chr5 | 92956835 | - |
| ChimerDB4 | LAML | TCGA-AB-2939 | CDC73 | chr1 | 193121574 | + | FAM172A | chr5 | 92956835 | - |
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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) |
| ENST00000367435 | CDC73 | chr1 | 193121574 | + | ENST00000509163 | FAM172A | chr5 | 92956835 | - | 1357 | 1156 | 7 | 1176 | 389 |
| 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 |
| ENST00000367435 | ENST00000509163 | CDC73 | chr1 | 193121574 | + | FAM172A | chr5 | 92956835 | - | 0.005220167 | 0.9947798 |
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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 >14942_14942_1_CDC73-FAM172A_CDC73_chr1_193121574_ENST00000367435_FAM172A_chr5_92956835_ENST00000509163_length(amino acids)=389AA_BP= MGGYCPCCCRRRGRLLVLLLLVRRGGEGGGGRGRGDKRRRRQARRQRRRPEPAEARGGKMADVLSVLRQYNIQKKEIVVKGDEVIFGEFS WPKNVKTNYVVWGTGKEGQPREYYTLDSILFLLNNVHLSHPVYVRRAATENIPVVRRPDRKDLLGYLNGEASTSASIDRSAPLEIGLQRS TQVKRAADEVLAEAKKPRIEDEECVRLDKERLAARLEGHKEGIVQTEQIRSLSEAMSVEKIAAIKAKIMAKKRSTIKTDLDDDITALKQR SFVDAEVDVTRDIVSRERVWRTRTTILQSTGKNFSKNIFAILQSVKAREEGRAPEQRPAPNAAPVDPTLRTKQPIPAAYNRYDQERFKGK -------------------------------------------------------------- |
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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/chr1:193121574/chr5:92956835) - 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 |
| CDC73 | FAM172A |
| FUNCTION: Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the cleavage and polyadenylation specificity factor (CPSF) complex and the cleavage stimulation factor (CSTF) complex, and with Wnt signaling. Involved in polyadenylation of mRNA precursors. {ECO:0000269|PubMed:15580289, ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15923622, ECO:0000269|PubMed:16630820, ECO:0000269|PubMed:16989776, ECO:0000269|PubMed:19136632, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879}. | FUNCTION: Plays a role in the regulation of alternative splicing, by interacting with AGO2 and CHD7. Seems to be required for stabilizing protein-protein interactions at the chromatin-spliceosome interface. May have hydrolase activity. {ECO:0000250|UniProtKB:Q3TNH5}. |
| 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 |
| Hgene | CDC73 | chr1:193121574 | chr5:92956835 | ENST00000367435 | + | 10 | 17 | 125_139 | 324.0 | 532.0 | Motif | Note=Nuclear localization signal |
| Tgene | FAM172A | chr1:193121574 | chr5:92956835 | ENST00000395965 | 9 | 11 | 413_416 | 369.3333333333333 | 417.0 | Motif | Prevents secretion from ER | |
| Tgene | FAM172A | chr1:193121574 | chr5:92956835 | ENST00000505869 | 7 | 9 | 413_416 | 259.3333333333333 | 307.0 | Motif | Prevents secretion from ER | |
| Tgene | FAM172A | chr1:193121574 | chr5:92956835 | ENST00000509163 | 8 | 10 | 413_416 | 323.3333333333333 | 371.0 | Motif | Prevents secretion from ER |
| - 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 | CDC73 | chr1:193121574 | chr5:92956835 | ENST00000367435 | + | 10 | 17 | 361_364 | 324.0 | 532.0 | Compositional bias | Note=Poly-Ile |
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Fusion Protein Structures |
| 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) | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | AA seq | Len(AA seq) |
| PDB file >>>775_CDC73_193121574_FAM172A_92956835_ranked_0.pdb | CDC73 | 193121574 | 193121574 | ENST00000509163 | FAM172A | chr5 | 92956835 | - | MGGYCPCCCRRRGRLLVLLLLVRRGGEGGGGRGRGDKRRRRQARRQRRRPEPAEARGGKMADVLSVLRQYNIQKKEIVVKGDEVIFGEFS WPKNVKTNYVVWGTGKEGQPREYYTLDSILFLLNNVHLSHPVYVRRAATENIPVVRRPDRKDLLGYLNGEASTSASIDRSAPLEIGLQRS TQVKRAADEVLAEAKKPRIEDEECVRLDKERLAARLEGHKEGIVQTEQIRSLSEAMSVEKIAAIKAKIMAKKRSTIKTDLDDDITALKQR SFVDAEVDVTRDIVSRERVWRTRTTILQSTGKNFSKNIFAILQSVKAREEGRAPEQRPAPNAAPVDPTLRTKQPIPAAYNRYDQERFKGK | 389 |
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pLDDT score distribution |
| 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. |
CDC73_pLDDT.png  |
FAM172A_pLDDT.png  |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
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Ramachandran Plot of Fusion Protein Structure |
| 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 |
| 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 |
| CDC73 | |
| FAM172A |
| - 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 |
| Hgene | CDC73 | chr1:193121574 | chr5:92956835 | ENST00000367435 | + | 10 | 17 | 200_531 | 324.0 | 532.0 | POLR2A and PAF1 |
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Related Drugs to CDC73-FAM172A |
| 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 CDC73-FAM172A |
| 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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